CN101036780A - Application of self-assembled short peptide in the medicine for treating burn and face wound - Google Patents
Application of self-assembled short peptide in the medicine for treating burn and face wound Download PDFInfo
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- CN101036780A CN101036780A CN 200710048975 CN200710048975A CN101036780A CN 101036780 A CN101036780 A CN 101036780A CN 200710048975 CN200710048975 CN 200710048975 CN 200710048975 A CN200710048975 A CN 200710048975A CN 101036780 A CN101036780 A CN 101036780A
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Abstract
本发明公开了自组装短肽RADA16－1在制备治疗烧伤创面的药物中的应用。本发明采用调温式电烫仪与火焰烧伤制造大鼠皮肤烧伤模型，以自组装短肽RADA16－1形成的水凝胶及常用的烧伤治疗药物壳聚糖、胶原、聚乳酸为敷料进行治疗实验，实验结果表明：自组装短肽RADA16－1可抑制烧伤创面的扩大和水肿、促进烧伤创面胶原的有序重排、促进烧伤创面愈合及皮肤和皮肤组织附属物的再生和修复，与壳聚糖、胶原、聚乳酸相比，对烧伤的疗效更好。The invention discloses the application of self-assembled short peptide RADA16-1 in the preparation of medicine for treating burn wounds. The present invention uses a temperature-regulating electric scald instrument and flame burns to manufacture a rat skin burn model, and uses the hydrogel formed by the self-assembled short peptide RADA16-1 and the commonly used burn treatment drugs chitosan, collagen, and polylactic acid as dressings for treatment experiments , the experimental results show that: the self-assembled short peptide RADA16-1 can inhibit the expansion and edema of burn wounds, promote the orderly rearrangement of collagen in burn wounds, promote the healing of burn wounds, and the regeneration and repair of skin and skin tissue appendages. Compared with sugar, collagen and polylactic acid, it has better curative effect on burns.
Description
Technical field
The present invention relates to the purposes of self-assembled short peptide RADA16-1, particularly the application in the medicine of preparation treatment burn wound.
Background technology
In engineering construction, commercial production and daily life, fire happens occasionally, and therefore has the injury of fire to human body inevitably, even do not produce fire, (for example electric welder, blast-furnace man's misoperation, household electrical appliance improper use etc.) also can cause the burn of human body in some cases.Serious burn patient's treatment time is long, complication is many, disability rate is high, particularly deep burn often causes having left over cicatrix in various degree after the recovery from illness, even disfeature have influence on attractive in appearance, serious situation can cause organization activity limited, afunction, even dysfunction and/or beauty treatment are corrected in the post-operative shaping, unfortunately many patients finally still leave over to a certain degree maimed and/or lopsided unavoidably, especially the face deep burn makes the patient's spirit and the human body bear very big misery owing to disfeature.Clinical a kind of desirable dressing flap coverage as early as possible of always seeking is avoided infection, thereby promotes the wound surface epidermal growth, recover skin function, reduce the wound surface cicatrix, further avoid MOFE as respiratory distress syndrome, intestinal dysfunction, disseminated inravascular coagulation.
Existing Wound dressing has traditional dressing, natural biological dressing, synthetic dressing.Traditional dressing comprises gauze, cotton pad, and shortcoming is the adhesion wound, and not every bacterium, moisture-retaining capacity is poor, and is hemostatic bad.Natural biological dressing comprises from body skin, alloskin, amniotic membrane, radiated pig skin, acellular dermis and collagen class, and it is limited to have a source, and immunogenicity is strong, carries drawbacks such as pathogen.Synthetic dressing is a raw material with the macromolecular material, exists biocompatibility poor, is difficult to degraded, problems such as strong toxicity.
Self-assembled short peptide (Self-assembly of peptides is called for short SAP) RADA16-1 is a kind of micromolecule polypeptide that contains 16 amino acid residues, and its aminoacid sequence is AcN-RADARADARADARADA-CONH
2(seeing that international publication number is WO 2005/014615 A2, was the patent application on February 17th, 2005 in international open day) in the patent application of publication number WO 2005/014615 A2, only briefly described this small peptide the cutting wound and wound surface had repair function.
Summary of the invention
The objective of the invention is to prove the new purposes of self-assembled short peptide RADA16-1 in pharmacy, burn wound provides a kind of eutherapeutic medicine for treatment.
In the past studies show that (Leila Cuttle, Margit Kempf, Gael E, Phillips, Julie Mill, Mark T.Hayes, JohnF.Fraser, Xue-Qing Wang, Roy M.Kimble..A porcine deep dermal partial thickness burn model withhypertrophic scarring.Burn 2006; 32:806-820..), burn wound repairs and is different from the incision wound repair.Because complication such as the inflammatory reaction of following behind dark II degree and III degree burn and the burn, traumatic infection edema can cause destructive infringement to organic epidermis, corium, wound surface has expansion to a certain degree after serious burn, depth of burn has to a certain degree progress, this deterioration can delay the epithelization process of wound repair, and incision then this phenomenon can not take place.Burn back is crucial by the progress that suppresses serious inflammation damnification and suppress depth of burn.
The present invention adopts temp .-regulating type permanent hair styling instrument and flame burn to make rat skin burn model, the hydrogel that forms with self-assembled short peptide RADA16-1 reaches burn treating medicine chitosan commonly used, collagen, polylactic acid is that dressing experimentizes, experimental result shows: self-assembled short peptide RADA16-1 can suppress the expansion and the edema of burn wound, promote the orderly rearrangement of burn wound's collagen, promote burn wound healing and skin and appendicular regeneration of skin histology and reparation, can coordinate wound surface epithelical cell growth factor (EGF), the secretion of basic fibroblast growth factor (FGF), with chitosan, collagen, polylactic acid is compared, to the better efficacy of burn.
The self-assembled short peptide RADA16-1 of described hydrogel form is prepared from by self-assembled short peptide RADA16-1 and pure water, the quality percent by volume of self-assembled short peptide RADA16-1 is 0.05%～10%, and pure water comprises distilled water, ultra-pure water (resistance 18.2K Ω/cm
2).
Invention has following beneficial effect:
1, the advantage of the animal model of burn of manufacturing of the present invention is, burn wound's condition equilibrium, quantitative analysis that helps testing and comparison, be convenient to observe the recovery and the regeneration of damaged tissues in time windows, by detailed pathological observation, can the impaired wound surface inflammation of clear demonstration ooze out that (impaired wound surface does not excise, this is one of this model beneficial effect of being different from holostrome skin excision model), inflammatory cell is assembled, wound surface collagen is repaired, and regeneration is reset, and create the dynamic process that the Zhou Jiankang epithelial cell is creeped and grown, can estimate the repair function of various materials to burn wound.
2, the present invention has excavated new medical application to self-assembled short peptide RADA16-1, has opened up a new application.
3, the present invention provides a kind of effectively new medicine to the treatment of burn, helps removing the misery of burn patient, makes its early recovery.
Description of drawings
Fig. 1 is the wound surface shrinkage factor curve of self-assembled short peptide RADA16-1 group, chitosan group, collagen group, polylactic acid group, blank group.
Fig. 2 is a haematoxylin dyeing pathology photo, wherein, A figure is that normal control, self-assembled short peptide RADA16-1 group and blank group are handled back three hours haematoxylin dyeing pathology photo in burn wound, top among the B figure is the haematoxylin dyeing pathology photo that self-assembled short peptide RADA16-1 organized the 70th day, and the bottom among the B figure is the 70th day a haematoxylin dyeing pathology photo of chitosan group.
Fig. 3 repairs I type in each, III Collagen Type VI displayed map with the deep ii degree burn of polarized light microscope observing in period, among the figure, (a) be self-assembled short peptide RADA16-1 group, (b) be the blank group, blank group and self-assembled short peptide RADA16-1 group compare, and picric acid celestine blue specific stain type i collagen is redness or orange colour, strong refractivity, III Collagen Type VI green, weak refractivity.
Fig. 4 is the collagen Pareto diagram of burn back regeneration skin wound, among the figure, (a) for self-assembled short peptide RADA16-1 group, (b) being the chitosan group, (c) is the normal control group, (d) be the blank group, self-assembled short peptide RADA16-1 forms face collagen and arranges near normal skin, and blank group and chitosan group show that the collagen arrangement is unordered, and the scarring tendency is arranged, present " singleization " vitreous degeneration, lack cutaneous appendages such as sweat gland.
Fig. 5 is the expression figure that basic fibroblast growth factor (FGF) and epithelical cell growth factor (EGF) are repaired burn wound, among the figure, (a) and (c) express for self-assembled short peptide RADA16-1 group FGF, (a) be the 7th day, (c) be the 10th day, (b) negative contrast, (d) and (f) be respectively the blank group the 7th day and the 10th day FGF expresses, (e) express for normal skin FGF, (ghi) be that EGF expresses, (g),, (h) be blank group the 7th day (i) for self-assembled short peptide RADA16-1 organizes the 14th day for self-assembled short peptide RADA16-1 organizes the 7th day.
Fig. 6 is the atomic force microscope shape appearance figure, (a) self-assembled short peptide RADA16-I 0.5% (5mg/ml), (b) type i collagen 0.5% (5mg/ml), (c) biological fluid dressing chitosan (5mg/ml)
Fig. 7 is a flame burn morphology photo, and the left side is the blank group, and the right is a self-assembled short peptide RADA16-1 group, and four photos all show the 4th day the wound surface in burn back.
Fig. 8 is the morphology photo that burn wound recovers, and each photo below is self-assembled short peptide RADA16-1 group among the figure, and the top is the chitosan group.
Fig. 9 is that burn wound's epithelization process is dynamically schemed, and among the figure, (a) is the wound left end, (b) is the wound right-hand member.
Figure 10 is that the 7th day self-assembled short peptide RADA16-I group and blank are formed the covering weave HE photo that dyes, and among the figure, the edema tape thickness is seen shown in the yellow arrows under the rat holostrome skin histology Musclar layer.
The specific embodiment
1, materials and methods
1.1 material
1.1.1 animal
Laboratory animal (SD rat) is from the West China Experimental Animal Center, and body weight allows animal adapt to a week at cleaning constant temperature (20 ℃ ± 2 ℃) constant humidity (humidity 50%) receptacle at 200 grams-290 grams before the experiment.Totally 92 animals, wherein, 80 are used for scald apparatus preparation burn model, and 12 are adopted flame burns preparation burn models.
During with scald apparatus preparation burn model, according to randomization, 3 animals of every kind of each time window of material, self-assembled short peptide RADA16-I, chitosan, collagen, blank group, polylactic acid be totally 15 of totally 5 kinds of materials.Design 3 time windows, be respectively the 7th, 10,14 days, each time window is put to death with the excessive anesthesia of 10% chloral hydrate.Get wound surface skin and wound Zhou Zhengchang skin is HE, mallory (collagen staining), day scarlet dyeing of wolf, immunohistochemical staining.In addition 15 animals are cooked wound surface and trace and write down the 4th, 7,10,14 respectively, and 18,21 days wound surface shrinks.Remaining 20 animals are cooked the 23rd, 28, and the pathological tissue of 60,70,80 days blank group and self-assembled short peptide RADA16-I group is observed.
1.1.2 experiment material
(Cambridge MA), is dissolved in the RADA16-1 solution that is mixed with quality percent by volume 1% (10mg/ml) in the distilled water to self-assembled short peptide RADA16-1:RADA16-1 dry powder available from 3DM Inc.
Collagen: use type i collagen, type i collagen available from serologicals company (Lake Placid, NY).100mg collagen is dissolved in the 28.65ml acetic acid (0.02N), and pH transfers to 4.41, working concentration 3.49mg/ml.
Chitosan: use be commercial goods biological fluid dressing chitosan (available from Zhejiang Academy of Medical Sciences scientific and technological development company).
Polylactic acid: use PLGA 90:10 (DL-lactic acid (90%)-Acetic acid, hydroxy-, bimol. cyclic ester (10%) copolymer, [intrinsic viscosity]=1.66 are available from Sigma company)
1.2 method
Experimental animal model: make rat skin burn model with temp .-regulating type permanent hair styling instrument, flame burn.
1.2.1 zoopery process
(1) processing procedure to animal comprises 10% chloral hydrate intraperitoneal injection of anesthesia, preserved skin, sterilization, scald preparation.Make burn wound's (92 ℃, 8 seconds, deep ii degree burn) of two sizes, depth of burn unanimity at every rat back spinal column lateral symmetry position with thermostatic type permanent hair styling instrument.Burn applies the described self-assembled short peptide RADA16-1 of above-mentioned 1.1.2 solution respectively at burn site after forming, collagen solution, biological fluid dressing chitosan and polylactic acid, and each wound surface 50 μ l, the blank group applies with normal saline.Afterwards, thin layer vaseline oil yarn covers.The postoperative recovery, infection.
(2) flame burn alcohol burner, 95% alcohol ignition, fixing rat, back down, fixedly alcohol burner and flame distance, flame continues 8 seconds at rat back, every rat back is made a wound surface, and burn applies the described self-assembled short peptide RADA16-1 of above-mentioned 1.1.2 solution, normal saline respectively at burn site after forming, form small peptide RADA16-1 group and blank group, method for subsequent processing is the same.
1.2.2 wound surface is traced and incrustation, molten crust time sheet
Trace the wound surface original size at that time in the preparation of temp .-regulating type permanent hair styling instrument burn, traced the wound surface size on the same day in the 4th, 7,10,14,18,21 day.Trace along the wound surface edge of rule with transparent film, use the scanner scanning film, image processing software calculates the wound surface area, calculates the wound surface shrinkage factor according to formula " 100% * (original wound surface area-actual measurement wound surface area)/original wound surface area ".The wound surface shrinkage factor adopts the relatively q check in twos between a plurality of sample averages between each time window group.
1-7 days (acute edema phase) carried out the wound surface observation behind the flame burn.
Take pictures every day, writes down the incrustation time that begins and the molten crust time of every animal burn wound respectively.
1.2.3 histological observation
The histological observation time window: temp .-regulating type permanent hair styling instrument was hindered the back the 7th, 8,10,14,21,23,28,60,70,80 day, and animal is put to death by excessive anesthesia respectively, gets wound surface skin and prepares tissue slice.
1.2.3.1 wound surface I type, III Collagen Type VI ratio detect
(1) gets burn wound's skin histology respectively at each time window, get 6 wound surface for every group;
(2) gradient dehydration, paraffin embedding, section, gradient dimethylbenzene takes off cured, and gradient ethanol takes off dimethylbenzene;
(3) cut into slices in distillation washing 3 times;
(4) immerse the blue solution of picric acid celestite (concentration 0.5%, w/v);
(5) haematoxylin dyeing showed cell nuclear;
(6) the dimethylbenzene gradient is soaked;
(7) gummy mounting;
(8) Olympus polarized light microscope observing, microphotograph, image processing software is handled image, and collagen content contrasts with aberration, and type i collagen is dyed yellow or Chinese red, is strong refractivity; The III Collagen Type VI is green and is weak refractivity, Image-pro plus image processing software Treatment Analysis deuteranomalia refractive power collagen content, and III Collagen Type VI content is x%, type i collagen content is (100-x) %, the SPSS software processes.Date processing is with independent sample mean one factor analysis of variance between each time period group.
1.2.3.2HE pathological staining
(1) paraffin embedding is fixed in burn position holostrome skin histology excision back dehydration in 4% paraformaldehyde;
(2) take off curedly, immerse and to take off cured liquid dimethylbenzene twice, each each 10 minutes;
(3) 100% absolute alcohol removal xylenes 5 minutes;
(4) 95% ethanol removal xylenes 2 minutes;
(5) 90% ethanol removal xylenes 2 minutes;
(6) 80% ethanol removal xylenes 2 minutes;
(7) washing goes ethanol to tasteless;
(8) the distillation washing once;
(9) 0.5% haematoxylin dyeings, room temperature 5-10 minute;
(10) washing;
(11) hydrochloride alcohol color separation;
(12) ammonia is short blue;
(13) 1% Yihong room temperature dyeing 5 minutes;
(14) 80% ethanol color separations;
(15) 90% dehydration of alcohols;
(16) 95% dehydration of alcohols;
(17) 100% dehydration of alcohols 5 minutes;
(18) dimethylbenzene is transparent 10 minutes;
(19) canada balsam mounting.
1.2.4 immunohistochemical staining
Temp .-regulating type permanent hair styling instrument burn back the 7th, 8,10,14,21,23,28,60 day, animal is put to death by excessive anesthesia respectively, gets wound surface skin and prepares tissue slice.
(1) skin histology gradient dehydration, paraffin embedding is fixed;
(2) section, the thick 5um of sheet;
(3) the anti-flake of microscope slide is handled, and the paraffin organization section that 5um is thick is mounted in the section of 3-aminopropyl three ethoxy silane (APES is available from Sigma company) silication, puts 37 ℃ of calorstats 48 hours;
(4) the section routine is taken off cured;
(5) gradient dimethylbenzene takes off curedly, and gradient ethanol takes off dimethylbenzene;
(6) the multiple antigen of hot repair: will cut into slices and immerse citrate buffer, electric furnace or microwave oven are heated to the outage of boiling back, and 1-2 time repeatedly, cooling back PBS washing 2 times;
(7) Dropwise 5 %BSA confining liquid, room temperature 20 minutes is got rid of unnecessary liquid, does not wash;
(8) drip one of dilution in 1: 100 and resist (mice or rabbit igg), 4 ℃ are spent the night, and PBS washes 2 minutes * 3 times;
(9) dripping the anti-mice IgG.PBS of biotinylated goat (pH7.2) washes 2 minutes * 3 times;
(10) drip reagent SABC, 20-37 ℃ 20 minutes, PBS washes 4 times;
(11) DAB colour reagent box is used in DAB colour developing;
(12) haematoxylin is slightly redyed, dehydration, transparent, mounting, and microscopic examination is taken a picture, and image processing software is analyzed the wound surface growth factor expression, weighs the expression of positive particle in the wound tissue cell with light absorption value.
1.2.5 edema quantitative measurement
(1) choose and scalded back 3 hours and each 6 of the 7th day blank matched group and self-assembled short peptide RADA16-I group skin samples, prepare 24 pathological sections, HE dyes the pathological section preparation method with above-mentioned;
(2) the Olympus optical microscope is taked image, and photo amplifies 10 times;
(3) adopt prescription length value in the Image-pro plus image analysis software computed image, 3 hours wound surface specimen are calculated epidermis thickness (see figure 2) to the Musclar layer, and specimen was calculated loose connective tissue thickness (see figure 10) under the Musclar layers in 7 days;
(4) 3 hours specimen are gathered blank group and self-assembled short peptide RADA16-I group sample 45 and 57 respectively, and 7 days specimen are gathered blank group and self-assembled short peptide RADA16-I group sample 167 and 154 respectively;
(5) two large sample means u-test is relatively adopted in contrast between the group.
1.2.6 atomic force microscope observation
(1) coating 5 μ l on fresh mica sheet, material is respectively collagen, chitosan, self-assembled short peptide RADA16-I;
(2) clean not adherent material with pure water;
(3) dry one hour naturally;
(4) (Seiko Instruments Inc., Chiba Japan) carries out with percussion mode with SPI4000 Probe Station and SPA-400 SPM Unit under the room temperature.
2, result
2.1 wound surface morphologic observation result
2.1.1 wound surface is traced the result
The wound surface shrinkage factor result of calculation of the animal burn model of temp .-regulating type permanent hair styling instrument preparation is seen Fig. 1, wound surface recovers to see Fig. 8, as can be seen from Figure 1, the wound surface shrinkage factor of self-assembled short peptide RADA16-1 group is higher than other each group, the 4th day, the 7th day of acute edema phase, collagen, chitosan, the blank group enlarges trend (wound surface shrinkage factor meansigma methods is negative value) owing to burn wound's edema presents wound surface, and self-assembled short peptide RADA16-1 forms face and still just shows as at these two observation windows and shrink.In the time of 21 days, the wound surface shrinkage factor of self-assembled short peptide RADA16-1 group is up to 80%, and other wound surface shrinkage factor of several groups is 45%-60%.To form face contraction, incrustation, molten crust situation good than the chitosan group for self-assembled short peptide RADA16-1 as can be seen from Figure 8.
The wound surface of the animal burn model of flame burn preparation shrinks sees Fig. 7, four photos show among Fig. 7, self-assembled short peptide RADA16-1 forms the face contraction and significantly speeds than the blank group, especially remarkable in the burn early-age shrinkage, acute edema phase (hindering the back the 4th day), face is formed in the small peptide treatment is not had expansion trend, and blank is formed the more original wound surface expansion of face 35%～50% (P＜0.05).
2.1.2 incrustation, molten crust time
Incrustation, molten crust time see Table 1.
Table 1 incrustation, molten crust time
| Experimental group | The incrustation time (my god) | The molten crust time (my god) |
| Small peptide RADA16-1 organizes (n=6) chitosan group 2 (n=6) polylactic acid group 3 (n=6) blank group (n=6) | 6 9 11 10 | 13 15* 18 16 |
P＜0.01，
*P＞0.05
As can be seen from Table 1, the incrustation time of self-assembled short peptide RADA16-1 group and molten crust time all are shorter than other each group.Prompting small peptide processed group burn wound skin regeneration speeds up, and healing time shortens.
2.2 histological observation result
2.2.1 wound surface I type, III Collagen Type VI ratio testing result
Wound surface III Collagen Type VI ratio testing result sees Table 2, and wound surface type i collagen ratio then is (100-x) %.Fig. 3 is seen in the demonstration of wound surface I type, III Collagen Type VI.
Each time period wound repairing III Collagen Type VI content ratio (small peptide and blank group) of table 2
| Experimental group | The 7th day III Collagen Type VI ratio % | The 10th day III Collagen Type VI ratio % | The 14th day III Collagen Type VI ratio % | The 30th day III Collagen Type VI ratio % |
| Small peptide RADA16-1 group blank group two-tailed test standard deviation | 33.748 ±16.41753 24.4290 ±11.47747 P＝0.024 | 50.2431 ±17.12478 38.5256 ±15.79507 P＝0.001 | 50.6088 ±14.31810 26.9947 ±13.05107 P＜0.001 | 50.5175 ±15.06343 16.4129 ±14.89894 P＝0.002 |
From table 2, Fig. 3 as can be seen, the wound surface III Collagen Type VI ratio of self-assembled short peptide RADA16-1 group is much larger than the blank group.The active proliferation of prompting small peptide processed group wound surface, it is little than the blank group that the reparation later stage forms the hypertrophic cicatrix risk.
2.2.2HE pathological staining result
The HE pathological staining the results are shown in Figure 2, Fig. 4, Fig. 9, and from Fig. 2 B top as can be seen, the 70th day, self-assembled short peptide RADA16-1 organized visible skin corium cutaneous appendage, body of gland, and hair follicle regeneration is abundant; From Fig. 2 B bottom as can be seen, the 70th day, the visible skin corium cutaneous appendage of chitosan group, but hair follicle lacks.The inventor has compared the hair follicle number of blank group and self-assembled short peptide RADA16-I group burn wound, 0～10 of the every low-power field of the newborn epidermis hair follicle number of blank group, and several 22～44 of every low-power field hair follicle, P＜0.01 are organized in the small peptide treatment.This results suggest small peptide uses can promote appendicular regeneration of burn wound's skin histology and reparation.
As can be seen from Figure 4, the 70th day, self-assembled short peptide RADA16-1 group (a) wound surface collagen was arranged near normal skin (c), blank group (d) and chitosan group (b) wound surface collagen are arranged unordered, the scarring tendency is arranged, present " singleization " vitreous degeneration, lack cutaneous appendages such as sweat gland.This results suggest small peptide uses promoting orderly rearrangement of wound surface collagen and the differentiation of skin affiliated group that obvious effect is arranged.
As can be seen from Figure 9, the downright bad exfoliation in burn back, newborn epithelial tissue is along the covering of creeping of leukocyte infiltration band.Clearly show the epithelization process of burn back epidermis cell from the deep skin differentiation.This results suggest, the burn model that this experiment is adopted can know that demonstration burn slough comes off, the dynamic process in each period that the differentiation of newborn epidermal tissue is creeped.Quantitative analysis that helps testing and comparison, and observe the recovery and the regeneration of damaged tissues in different time sections, by detailed pathological observation, can the impaired wound surface inflammation of clear demonstration ooze out (impaired wound surface does not excise, and this is one of this model beneficial effect of being different from holostrome skin excision model).
2.3 immunohistochemical staining result
Immunohistochemical staining the results are shown in Figure 5, as can be seen from Figure 5, self-assembled short peptide RADA16-1 organizes the brown dense positive particle that dyes and is deposited on epidermis cell, fibroblast and the body of gland, and blank group positive expression rate is starkly lower than RADA16-1 small peptide group (absorbance), (P＜0.05).
The inventor uses the secretion that basic fibroblast growth factor in the wound tissue (FGF) and epithelical cell growth factor (EGF) have detected in streptomycin peroxidase complex immunity histochemical method.Discovery is repaired phase self-assembled short peptide RADA16-1 group FGF and (than blank) obviously increased in these two kinds of somatomedin expression on blood vessel and body of gland of EGF to some extent at inflammation edema phase and collagen, but FGF does not continue the trend (FGF continues high expressed has scarring to form trend) that increases.Prompting small peptide processed group growth factor expression has good regulating action to wound repair.
2.4 edema testing result
The edema testing result is seen Fig. 2 A and Figure 10, as can be seen from Figure 2A, calculate wound surface specimen epidermis thickness to the Musclar layer that scald wound was handled 3 hours, find self-assembled short peptide RADA16-1 group almost with the normal control zero difference, and blank group and normal control are widely different, this results suggest self-assembled short peptide RADA16-1 can obviously suppress to burn edema degree of skin wound.As can be seen from Figure 10, the 7th day, (P＜0.01, blank group skin histology was the transition inflammatory reaction to the obviously blank group minimizing of edema tape thickness (shown in the yellow arrows) under the rat holostrome skin histology Musclar layer that self-assembled short peptide RADA16-1 organizes.This results suggest, the self-assembled short peptide RADA16-1 skin wound that can obviously suppress to burn is repaired the edema degree of inflammatory phase.
2.5 atomic force microscope observation result
The atomic force microscope observation result is shown in Fig. 6, table 3.
As can be seen from Figure 6, self-assembled short peptide RADA16-1 (a) can form evenly thick fiber and keep the surface of good porosity, and type i collagen (b), biological fluid dressing chitosan (c) then form irregular ball lamellar and assemble (P=0.01).Prompting small peptide RADA16-1 has the high ventilation performance as medicines dressing.
As can be seen from Table 3, along with concentration reduces gradually, small peptide RADA16-1 still keeps good fiber condition, and surface porosity factor descends gradually, and type i collagen, biological fluid dressing chitosan can not form good fiber condition when concentration reduces gradually, and its surface porosity factor does not descend gradually with Concentraton gradient and presents variation tendency clocklike.Prompting small peptide RADA16-1 is diluted gradually and the dressing dilution factor near wound surface is big more more after absorbing sepage as medicines dressing, forms the Concentraton gradient that from the superficial to the deep reduces gradually on the wound surface surface and changes.
Table 3 characterizes (porosity) with the fibre morphology that Concentraton gradient changes the nanoscale three-dimensional stent material
| Concentration (mg/ml) | RADA16-I porosity (%) | Type i collagen porosity (%) | Biological fluid dressing chitosan porosity (%) |
| 10mg/ml 5mg/ml (0X diluted) 1mg/ml (5x diluted) 0.17mg/ml (10x diluted) | 49～70 17～43 37～52 12～28 | 18～30 32～51 4～7 | ～4 1～10 4～8 |
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