CN115317472A - Application of ResolvinD1 in preparation of medicine for relieving intestinal apoptosis - Google Patents

Abstract

The invention discloses an application of ResolvinD1 in preparing a drug for relieving intestinal cell apoptosis. The slow-release effect of ResolvinD1 on intestinal cell apoptosis in the present invention is to down-regulate the expression of GRP78 gene and Caspase-3 gene and up-regulate Bcl-2 gene expression, thereby slowing down the apoptosis of intestinal cells.

Description

Application of ResolvinD1 in the preparation of drugs for alleviating intestinal cell apoptosis

technical field

The invention relates to the technical field of biomedicine, in particular to the application of ResolvinD1 in the preparation of drugs for alleviating intestinal cell apoptosis.

Background technique

The intestinal epithelium is the first line of defense against the invasion of pathogens in the intestinal barrier of animals, and has a well-developed endoplasmic reticulum structure. The endoplasmic reticulum is involved in the biosynthesis, folding, processing, and modification of soluble and membrane proteins, and is also an important site for regulating calcium ion storage and lipid (cholesterol, steroid) anabolism. Numerous cell populations of the intestinal epithelium also depend on ER homeostasis for their normal function and the stability of the intestinal barrier.

Piglets are stimulated by various physiological or pathological factors such as early weaning, pathogenic bacteria invasion (mainly stimulated by Escherichia coli and its cell wall component lipopolysaccharide (LPS)) and nutritional deficiencies, which easily lead to endoplasmic reticulum stress and its mediated intestinal epithelial cell damage. Apoptosis, which in turn leads to intestinal epithelial cell damage and intestinal barrier damage. Therefore, reducing endoplasmic reticulum stress and its mediated intestinal epithelial cell apoptosis is of great significance for protecting animal intestinal health and preventing intestinal diseases.

Resolvin is a class of biologically active lipid mediators derived from n-3 polyunsaturated fatty acids. Current research on the regulation of Resolvin on the intestinal barrier is mainly focused on inflammatory pathological models. Studies have shown that Resolvin D1 (abbreviated as RvD1) can reduce inflammation in colitis mice by inhibiting the NLRP3 inflammasome signaling pathway; specifically, Resolvin D1 treatment induced the expression of intestinal alkaline phosphatase and enhanced its activity, it has the ability to protect the intestinal mucosa from cellular lipopolysaccharide damage, thereby improving intestinal inflammation in colitis mice.

Although current studies have shown that Resolvin can reduce intestinal inflammation and maintain intestinal barrier health, the effect of Resolvin on intestinal epithelial cell apoptosis mediated by endoplasmic reticulum stress is still unclear.

Contents of the invention

In view of the above-mentioned problems in the prior art, the present invention provides an application of ResolvinD1 in the preparation of a drug for alleviating intestinal cell apoptosis.

In order to achieve the above object, the technical solution adopted by the present invention to solve the technical problems is:

Application of ResolvinD1 in preparation of medicine for alleviating intestinal cell apoptosis.

The beneficial effects of the present invention are as follows: ResolvinD1 in the medicament of the present invention inhibits the expression of the endoplasmic reticulum stress gene GRP78 and the apoptosis gene Caspase-3, and at the same time promotes the expression of the anti-apoptosis gene Bcl-2, thereby slowly releasing intestinal cells apoptosis.

On the basis of above-mentioned technical scheme, the present invention can also be improved as follows:

Furthermore, the drug slows down intestinal cell apoptosis by down-regulating the expression of GRP78 gene and Caspase-3 gene and up-regulating the expression of Bcl-2 gene.

Further, the drug slows down intestinal cell apoptosis by inhibiting the expression of GRP78 gene mRNA.

Furthermore, the drug slows down intestinal cell apoptosis by inhibiting the mRNA expression of Caspase-3 gene.

Further, the drug slows the release of intestinal cell apoptosis by promoting the mRNA expression of Bcl-2 gene.

Furthermore, the drug slows down intestinal cell apoptosis by inhibiting the expression of GRP78 protein.

Further, the drug slows the release of intestinal cell apoptosis by inhibiting the expression of Caspase-3 protein.

Further, the drug slows the release of intestinal cell apoptosis by promoting the expression of Bcl-2 protein.

Furthermore, a drug for alleviating intestinal cell apoptosis, the main active ingredient is ResolvinD1.

The present invention has the following beneficial effects:

The present invention uses the biologically active lipid medium ResolvinD1 to alleviate the apoptosis of intestinal cells in animals, and not only obtains a new method for maintaining the normal function of animal intestinal barrier and protecting intestinal health, but also the biologically active substance is non-toxic Side effects, to some extent reduce the use of chemicals such as antibiotics.

In the present invention, the endoplasmic reticulum stress-apoptosis model of intestinal epithelial cells was first constructed by tunicamycin stimulation, and on this basis, different concentrations of ResolvinD1 were used to relieve the stress. NET stress and apoptosis, and the early, late and total apoptosis rates were reduced by 21.67%, 29.67% and 26.03% (P<0.05); the results of experiments on mice showed that ResolvinD1 treatment made mice adopt Food intake increased by 10.05% (P<0.05), the depth of jejunal crypts decreased by 15.21% (P<0.05), and the apoptosis rate of jejunal epithelial cells decreased by 32.28% (P<0.05). In the present invention, the mechanism of ResolvinD1 slowing the release of intestinal cell apoptosis is that ResolvinD1 is closely related to the down-regulation of the expression of the endoplasmic reticulum stress gene GRP78 and the apoptosis gene Caspase-3 and the up-regulation of the expression of the anti-apoptosis gene Bcl-2, Specifically: ResolvinD1 inhibits the expression of the endoplasmic reticulum stress gene GRP78 and the apoptosis gene Caspase-3, while promoting the expression of the anti-apoptosis gene Bcl-2.

Description of drawings

Figure 1 is the endoplasmic reticulum stress-apoptosis model of intestinal epithelial cells induced by tunicamycin, wherein, A in Figure 1 is the protein band of GRP-78 and internal reference gene Gapdh under different concentrations of tuni treatment, and in Figure 1 Figure B shows the relative expression of GRP-78 protein under different concentrations of tuni treatment. Figure C in Figure 1 shows the protein bands of GRP-78 and the internal reference gene Gapdh under different treatment times of tuni. Figure D in Figure 1 shows the different levels of tuni The relative expression of GRP-78 protein under the treatment time, the E picture in Figure 1 is the AO/EB staining result picture of normal cells and cells treated with 1 μg/mL tuni for 9h;

Figure 2 shows the toxicity detection of ResolvinD1 and its effect on cell viability, wherein, Figure A in Figure 2 is the release rate of LDH under different concentrations of ResolvinD1, and Figure B in Figure 2 is the cell viability rate under different concentrations of ResolvinD1;

Figure 3 is the determination of the effective concentration of ResolvinD1 in relieving endoplasmic reticulum stress and apoptosis, wherein, Figure A in Figure 3 is the cell viability (%) treated with different concentrations of ResolvinD1 under tuni stimulation, and Figure 3 in Figure 3 It is the mRNA relative expression level of GRP-78 gene, and the C figure among Fig. 3 is the mRNA relative expression level of Caspase-3 gene;

Figure 4 shows that ResolvinD1 alleviates the intestinal epithelial cell apoptosis induced by endoplasmic reticulum stress, wherein, 4-1 in Figure 4 is the result of AO/EB staining, and 4-2 in Figure 4 is the result of flow cytometry detection, Figure 4 4-3 in 4 is the apoptosis rate;

Figure 5 shows the mRNA expression levels of endoplasmic reticulum stress and apoptosis-related genes;

Figure 6 is the expression levels of endoplasmic reticulum stress and apoptosis-related proteins;

Fig. 7 is a result figure of mouse body weight and feed intake, wherein, the A graph in Fig. 7 is the feed intake result, and the B graph in Fig. 7 is the end-of-test mouse body weight result;

Figure 8 shows the effect of ResolvinD1 on mouse jejunum cell apoptosis, wherein, Figure A in Figure 8 is the result of Tunel detection, and Figure B in Figure 8 is the result of the apoptosis rate of small intestinal cells;

Figure 9 is the effect of ResolvinD1 on the morphology of mouse jejunum tissue, wherein, Figure A in Figure 9 is a morphological diagram of mouse jejunum tissue, and Figure B in Figure 9 is a measurement map of crypt depth and villi height;

Figure 10 is the effect of ResolvinD1 on the intestinal barrier function of mice, wherein, Figure A in Figure 10 is the concentration test results of diamine oxidase (DAO) and D-lactic acid (D-LA) in the blood, in Figure 10 Figure B is the test results of the mRNA expression levels of ZO-1 and Claudin-12 in the jejunum tissue;

Figure 11 shows the expression levels of genes related to endoplasmic reticulum stress and apoptosis in mouse intestinal cells.

Detailed ways

The application of ResolvinD1 in the present application in the preparation of drugs for alleviating intestinal cell apoptosis will be described below with reference to examples.

This application may, however, be illustrated in many different forms and should not be construed as limited to the specific embodiments set forth herein; rather, these embodiments are provided so that this application will be thorough and complete, and This will fully convey the scope of this application to those skilled in the art.

In the present invention, the regulation effect of ResolvinD1 on intestinal epithelial cell apoptosis and intestinal barrier mediated by endoplasmic reticulum stress is explored through in vivo and in vitro experiments. Specifically: the IPEC-J2 porcine small intestinal epithelial cell line and C57BL/6J mice were used as the research objects, and the endoplasmic reticulum stress-apoptosis model was established by tunicamycin (tunicamycin, tuni) stimulation. Based on the research on the effect of ResolvinD1 intervention on intestinal cell apoptosis and intestinal barrier.

1. In vitro study of the effect of ResolvinD1 on the apoptosis of porcine epithelial cells induced by endoplasmic reticulum stress:

(1) Model construction: detection of the expression of endoplasmic reticulum stress marker gene GRP78 in pig intestinal epithelial cells with different concentrations of tunicamycin (0, 0.5, 1, 2 μg/mL) and different treatment times (6, 9, 12, 15 h) , Concentration and time for constructing endoplasmic reticulum stress model.

(2) Cytotoxicity of ResolvinD1 and its effect on cell viability: detect the effect of ResolvinD1 concentration (1, 10, 20, 50 nM) on cytotoxicity and cell viability, and determine the effect concentration of ResolvinD1 on intestinal epithelial cells.

(3) To explore the effect of ResolvinD1 on intestinal epithelial cell apoptosis: flow cytometry, AO/EB staining, RT-qPCR, Western-Blotting and other techniques were used to analyze the effect of ResolvinD1 on the apoptosis rate and endoplasmic reticulum of porcine jejunum epithelial cells The mRNA and protein expression levels of stress key genes (GRP78, IRE1α, PERK, ATF-6, and CHOP) and apoptosis pathway marker genes (Caspase3, BAX, Bcl-2).

2. In vivo verification of ResolvinD1's relieving effect on endoplasmic reticulum stress-mediated apoptosis of mouse intestinal epithelial cells:

Detect the effect of ResolvinD1 on the body weight and feed intake of mice stimulated by tunicamycin; use Tunel staining to observe the effect of ResolvinD1 on the apoptosis of intestinal epithelial cells stimulated by tunicamycin; use HE staining, ELISA, RT-qPCR, etc. technique, analyzing the effect of ResolvinD1 on intestinal epithelial morphology and intestinal barrier in tunicamycin-stimulated mice.

Example

Example 1

Construction of endoplasmic reticulum stress-apoptosis model of intestinal epithelial cells:

Detect the expression of endoplasmic reticulum stress marker gene GRP78 in porcine intestinal epithelial cells with different concentrations of tunicamycin (0, 0.5, 1, 2 μg/mL) and different treatment times (6, 9, 12, 15 h), and screen to construct the endoplasmic reticulum Effect concentration and time of stress model.

The results of the construction of the intestinal epithelial cell endoplasmic reticulum stress-apoptosis model in this example are shown in FIG. 1 . It can be seen from Figure 1A-B that 0.5, 1 and 2 μg/mL tuni all significantly up-regulated the expression of the endoplasmic reticulum stress protein GRP-78, and the difference between 1 and 2 μg/mL tuni treatment was not significant, so the test chose 1 μg /mL as the concentration of tuni. It can be seen from Figure 1C-D that 6, 9, 12, and 15h tuni treatments all significantly up-regulated the expression of the endoplasmic reticulum stress protein GRP-78, and there was no significant difference between 9, 12, and 15h tuni treatments, so 9h was chosen for the experiment Acts as a tuni time. It can be seen from Figure 1E that, compared with normal cells, the cells showed bright green fluorescence after 1 μg/mL tuni treatment for 9 hours, and the cells had obvious apoptosis. The above research results indicated that treatment with 1 μg/mL tunicamycin for 9 hours could induce endoplasmic reticulum stress and apoptosis in intestinal epithelial cells.

Example 2

ResolvinD1 toxicity assay and its effect on cell viability:

Using different concentrations (1, 10, 20, 50nM) of ResolvinD1 to treat intestinal epithelial cells for 24h, the results are shown in Figure 2, wherein, Figure A in Figure 2 is a graph of the release rate of LDH under different concentrations of ResolvinD1, and Figure B is The graph of cell viability under different concentrations of ResolvinD1. Combining Figures A and B in Figure 2, it can be found that there is no difference in cell viability, and neither ResolvinD1 nor cytotoxicity.

Example 3

Concentration screening of ResolvinD1 for relieving endoplasmic reticulum stress and apoptosis:

Different concentrations (1, 10, 20, 50nM) of ResolvinD1 were used to treat intestinal epithelial cells stimulated with a concentration of 1 μg/mL tunicamycin, and the viability of intestinal epithelial cells was observed. The results are shown in Figure 3, wherein, A The picture shows the cell viability (%), the picture B shows the relative mRNA expression of the GRP-78 gene, and the picture C shows the relative mRNA expression of the Caspase-3 gene.

It can be seen from Figure 3 that ResolvinD1 at a concentration of 1nM and 10nM significantly alleviated the inhibitory effect of tunicamycin on the proliferation of intestinal epithelial cells, and both 1nM and 10nM ResolvinD1 significantly alleviated the inhibition of the endoplasmic reticulum marker gene GRP78 induced by tunicamycin. and up-regulation of the mRNA expression level of the apoptosis gene Caspase-3.

According to the research results in this example, 1 nM of ResolvinD1 was used as the concentration for alleviating endoplasmic reticulum stress and apoptosis in subsequent examples.

Example 4

ResolvinD1 alleviates endoplasmic reticulum stress-induced apoptosis in intestinal epithelial cells:

Treat intestinal epithelial cells with 1 μg/mL tunicamycin for 9 hours to stimulate endoplasmic reticulum stress and apoptosis, and then use 1 nM ResolvinD1 to alleviate the stimulation of tunicamycin on endoplasmic reticulum stress and apoptosis , and the result is shown in Figure 4.

It can be seen from 4-1 of Figure 4 that ResolvinD1 alleviates the apoptosis of intestinal epithelial cells induced by tunicamycin; Compared with the treatment group, the early, late and total apoptosis rates of the tunicamycin+ResolvinD1 group were significantly reduced, respectively by 21.67%, 29.67% and 26.03% (P<0.05), indicating that ResolvinD1 significantly alleviated the intestinal epithelial Apoptosis.

Example 5

ResolvinD1 reduces the expression of genes related to endoplasmic reticulum stress and apoptosis:

In order to explore the mechanism and pathway of ResolvinD1 in alleviating endoplasmic reticulum stress and apoptosis in IPEC-J2 cells, in this example, PCR and Western Blotting techniques were used to detect the key genes of endoplasmic reticulum stress (GRP78, IRE1α, PERK, ATF-6 and CHOP) and the mRNA and protein expression levels of apoptosis pathway marker genes (Caspase3, BAX, Bcl-2), the results are shown in Figure 5 and Figure 6.

As shown in Figure 5, PCR results indicated that tunicamycin treatment up-regulated the mRNAs of IRE-1a, PERK, ATF-6, CHOP, GRP78, Caspase-3 and BCL-2 in IPEC-J2 cells compared with the control group Expression level (P<0.05). Compared with the tunicamycin treatment group, the ResolvinD1+tunicamycin group significantly reversed the mRNA expression levels of GRP78 and Caspase-3 in the cells (P<0.05), and significantly increased the mRNA expression levels of the anti-apoptotic gene Bcl-2 in the cells (P<0.05), but did not affect the mRNA expression levels of PERK, IRE-1α and CHOP.

As shown in Figure 6, compared with the control group, the protein expression of Caspase-3 and GRP78 in the tunicamycin treatment group was significantly increased (P<0.05), and the expression of Bcl-2 protein was significantly decreased (P<0.05).

Compared with the tunicamycin treatment group, ResolvinD1+tunicamycin treatment significantly decreased the expression levels of Caspase-3 protein and GRP78 protein in cells (P<0.05), and significantly increased the protein expression level of BCL-2 (P<0.05).

Example 6

Effect of ResolvinD1 on mouse body weight and food intake:

The results of the effect of ResolvinD1 on the body weight and feed intake of mice are shown in Figure 7, where Figure A is the effect of ResolvinD1, tunicamycin and ResolvinD1+tunicamycin on the feed intake of mice, and Figure B is ResolvinD1, tunicamycin Effects of mycin and ResolvinD1+tunicamycin on body weight of mice.

It can be seen from Figure 7 that intraperitoneal injection of 1 mg/kg tunicamycin to mice for 16 hours had no significant effect on the body weight of the mice, but induced a decrease in the feed intake of the mice; while ResolvinD1 significantly alleviated the stimulation of tunicamycin. Feed intake decreased.

Example 7

ResolvinD1 relieves endoplasmic reticulum stress-induced apoptosis in mouse jejunum:

DNA fragmentation is a feature of late cell apoptosis. In this example, Tunel can be used to detect the fragmentation of nuclear DNA in the cell during apoptosis. Under fluorescent conditions, the nucleus of apoptotic cells shows green fluorescence, while the nucleus of normal cells Fluorescent blue. In addition, normal cells and apoptotic cells were manually counted, and the percentage of apoptotic cells was calculated, wherein, the percentage of apoptotic cells=apoptotic cells/(normal cells+apoptotic cells).

ResolvinD1 in this example relieves the mouse jejunal cell apoptosis research induced by endoplasmic reticulum stress as shown in Figure 8; it can be seen from A in Figure 8 that the control group mice and ResolvinD1 group mice jejunum cell apoptosis The nuclei all showed blue fluorescence, and almost no nuclei showed green fluorescence; the proportion of jejunum cell nuclei in the tunicamycin group showed green fluorescence increased; than decrease. From the manual counting data in Figure B in Figure 8, compared with the control group mice, the jejunum cell rate in the ResolvinD1 group did not change significantly; among them, compared with the control group mice, tunicamycin alone stimulated The apoptosis rate of mouse jejunum cells was increased by 2.59 times (P<0.05). Compared with the mice in the tunicamycin group, the apoptosis rate of jejunal cells in the ResolvinD1+tunicamycin combined treatment group decreased by 32.28% (P<0.05).

The above results indicated that ResolvinD1 significantly alleviated tunicamycin-induced intestinal endoplasmic reticulum stress and apoptosis in mice.

Example 8

ResolvinD1 on the morphology of mouse jejunum and intestinal barrier function:

In this example, the effect of ResolvinD1 on the morphology of mouse jejunum tissue and intestinal barrier function was first studied by observing the morphology of mouse jejunum tissue by HE staining and measuring the depth of crypts and the height of villi. The results are shown in FIG. 9 .

It can be seen from Figure A in Figure 9 that compared with mice in the control group, the intestinal villi of the mice in the tunicamycin group were less dense and less complete; compared with the mice in the tunicamycin group, ResolvinD1+coated The intestinal villi of the mice in the mycin group were denser and had increased integrity.

From the measurement data in panel B in Figure 9, compared with the control group mice, stimulation with tunicamycin alone caused the jejunal crypt depth of the mice to increase by 25.84% (P<0.05). Compared with the mice in the tunicamycin group, the jejunal crypt depth of the mice in the ResolvinD1+tunicamycin combined treatment group decreased by 15.21% (P<0.05). In addition, there were no significant differences in villi height and villi height/crypt depth in the jejunum of mice in different treatment groups.

In addition, the concentration of diamine oxidase (DAO) and D-lactic acid (D-LA) in the blood of each group of mice was also tested in this embodiment, as well as the concentration of ZO-1 and Claudin-12 in the jejunum tissue of each group of mice The mRNA expression level of the test results are shown in Figure 10.

Since the concentrations of diamine oxidase (DAO) and D-lactic acid (D-LA) in the blood reflect the integrity of the animal intestine to a certain extent, when the animal intestine is damaged and the intestinal permeability increases, The concentration of DAO and D-LA in the blood will increase accordingly. The concentration test results of diamine oxidase (DAO) and D-lactic acid (D-LA) in the blood of each group of mice in this example are shown in Figure 10A, but it can be seen from Figure 10A that DAO in the blood of each group of mice and D-LA concentration did not have significant difference.

Since Claudin and ZO are the main components of tight junctions, they are involved in maintaining the structural integrity, adhesion and function of the tight junction barrier in the animal intestine. The test results of the mRNA expression levels of ZO-1 and Claudin-12 in the jejunum tissues of mice in each group in this example are shown in FIG. 10B .

It can be seen from FIG. 10B that, compared with the control group mice, stimulation with tunicamycin alone significantly reduced the mRNA expression of ZO-1 in the jejunum tissue of the mice by 29.63% (P<0.05). Compared with the mice in the tunicamycin group, the mRNA expression of ZO-1 in the jejunum tissue of the mice in the ResolvinD1+tunicamycin combined treatment group was up-regulated by 18.24% (P=0.095).

Compared with the mice in the control group, stimulation with tunicamycin alone reduced the mRNA expression of Claudin-12 in the jejunum tissue of the mice by 25.41% (P=0.056); compared with mice in the tunicamycin group, ResolvinD1+tunicamycin The mRNA expression of Claudin-12 in the jejunum tissue of the combined treatment group was up-regulated by 16.78%, but the difference was not significant.

In summary, tunicamycin stimulation alone significantly destroyed the morphology of mouse jejunum tissue, increased the depth of mouse jejunal crypts, and decreased the mRNA expression levels of tight junction proteins ZO-1 and Claudin-12 in mouse jejunum, while ResolvinD1 Treatment protected tunicamycin from damaging effects on mouse jejunum morphology and intestinal barrier function.

Example 9

Effect of ResolvinD1 on expression of genes related to endoplasmic reticulum stress and apoptosis in mouse jejunum cells:

In this example, the research results of ResolvinD1 on the expression of genes related to endoplasmic reticulum stress and apoptosis in mouse jejunum cells are shown in FIG. 11 . It can be seen from Figure 11 that there was no significant difference in the expression levels of endoplasmic reticulum stress and apoptosis-related genes in the jejunum tissues of the mice in the control group and the ResolvinD1 group; compared with the mice in the control group, ATF-6 was significantly up-regulated in the tunicamycin group , PERK, GRP78, CHOP and Caspase-3 relative mRNA expression levels (P<0.05), significantly reduced Bcl-2/Bax (P<0.05). Compared with the tunicamycin treatment group, the combined treatment of ResolvinD1+tunicamycin significantly down-regulated the mRNA expression levels of GRP78, CHOP, and Caspase-3 (P<0.05), and increased Bcl-2/Bax (P<0.05); further It shows that the slow-release effect of ResolvinD1 on intestinal cell apoptosis is to inhibit the expression of GRP78 gene and Caspase-3 mRNA, and promote the expression of Bcl-2 mRNA.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection of the present invention. within range.

Claims (9)

1. Application of ResolvinD1 in preparing medicine for relieving intestinal apoptosis is provided.
2. 2. The use of ResolvinD1 in the preparation of a medicament for alleviating apoptosis in intestinal tract cells according to claim 1, wherein the medicament has a sustained release effect on apoptosis in intestinal tract cells by down-regulating the expression of GRP78 gene and Caspase-3 gene and up-regulating the expression of Bcl-2 gene.
3. 3. The use of ResolvinD1 according to claim 2 in the preparation of a medicament for the relief of apoptosis in intestinal cells, wherein the medicament is for the sustained release of apoptosis in intestinal cells by inhibiting the expression of GRP78 gene mRNA.
4. 4. The use of ResolvinD1 in the preparation of a medicament for alleviating intestinal apoptosis according to claim 2, wherein the medicament has a sustained release effect on intestinal apoptosis by inhibiting mRNA expression of Caspase-3 gene.
5. 5. The use of ResolvinD1 in the preparation of a medicament for alleviating apoptosis in intestinal tract according to claim 2, wherein the medicament has a sustained release effect on apoptosis in intestinal tract by promoting the expression of mRNA of the Bcl-2 gene.
6. 6. The use of ResolvinD1 according to claim 2 in the preparation of a medicament for the alleviation of intestinal apoptosis, wherein the medicament exerts a sustained-release effect on intestinal apoptosis by inhibiting the expression of GRP78 protein.
7. 7. The use of ResolvinD1 in the preparation of a medicament for alleviating apoptosis in intestinal cells according to claim 2, wherein the medicament exerts a sustained release effect on apoptosis in intestinal cells by inhibiting the expression of Caspase-3 protein.
8. 8. The use of ResolvinD1 according to claim 2 in the preparation of a medicament for alleviating apoptosis in intestinal cells, wherein the medicament has a sustained release effect on apoptosis in intestinal cells by promoting expression of Bcl-2 protein.
9. 9. A medicine for relieving intestinal apoptosis is characterized in that the main active ingredient is ResolvinD1.

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