CN118962136B - Application of PRDX2 as a biomarker in the auxiliary diagnosis and prognosis prediction of acute kidney injury - Google Patents
Application of PRDX2 as a biomarker in the auxiliary diagnosis and prognosis prediction of acute kidney injury Download PDFInfo
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Abstract
本发明提供PRDX2作为生物标志物在急性肾损伤辅助诊断和预后预测中的应用。具体涉及，检测生物标志物PRDX2表达量的试剂在制备急性肾损伤辅助诊断和预后预测产品中的应用。本发明首次发现急性肾损伤患者样本中的PRDX2存在差异表达，这样，PRDX2能够作为急性肾损伤的生物标志物，用于辅助诊断急性肾损伤或预后预测，为急性肾损伤的诊断及预测预后提供了新途径。
The present invention provides the use of PRDX2 as a biomarker in the auxiliary diagnosis and prognosis prediction of acute kidney injury. Specifically, it relates to the use of a reagent for detecting the expression amount of the biomarker PRDX2 in the preparation of an auxiliary diagnosis and prognosis prediction product for acute kidney injury. The present invention is the first to discover that there is differential expression of PRDX2 in samples of patients with acute kidney injury. In this way, PRDX2 can be used as a biomarker for acute kidney injury, for auxiliary diagnosis of acute kidney injury or prognosis prediction, and provides a new approach for the diagnosis and prognosis prediction of acute kidney injury.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of PRDX2 serving as a biomarker in auxiliary diagnosis and prognosis prediction of acute kidney injury.
Background
Acute kidney injury (acute kidney injury, AKI) is a clinical syndrome characterized by a rapid decline in renal function, manifested by a rapid increase in serum creatinine with or without a rapid decrease in urine volume. The incidence of AKI in inpatients is 10% -15%, and the incidence of AKI in intensive care unit patients can exceed 50%. At present, treatment means for AKI are still very deficient, about 200 thousands of patients die annually due to concurrent AKI, and the death rate is close to 50% -70%. In addition, the risk of developing Chronic Kidney Disease (CKD) in AKI survivors increases by about 4-fold, resulting in an increase in the risk of CKD progression by about 2.4-fold, which has become a socially heavy burden. Therefore, the deep understanding of the pathogenesis of AKI, the mining of new targets for AKI early diagnosis and therapeutic intervention, and the method has great significance in reducing the risk and burden brought by AKI.
The proximal tubular epithelial cells are extremely susceptible to various stimuli such as ischemia, nephrotoxic drugs, sepsis, etc., due to high energy requirements and unique microvascular environments, and sustained stimulation results in irreversible tubular injury. In the ischemia reperfusion, sepsis, cisplatin, folate-induced AKI model, iron death and apoptosis of proximal tubular epithelial cells were all observed, and are key events in AKI tubular cell injury and inflammation initiation.
Peroxo-reduced protein 2 (Peroxiredoxin, PRDX 2) belongs to the Peroxiredoxins superfamily and is a typical 2-Cys antioxidant protein of the peroxo-reduced protein family. The protein is mainly expressed in the cytoplasm and maintains cellular redox homeostasis by lowering peroxide levels. Intracellular expression of PRDX2 plays an important role in maintaining normal function of heart, kidney and muscle tissue. Redox imbalance of cells initiates iron death and apoptosis programs. PRDX2 has no typical signal peptide sequence and can be released extracellular by a non-classical secretory pathway mediated by vesicles, and both inflammation and oxidants can stimulate extracellular secretion of PRDX 2. PRDX2 can be used as a biomarker for screening altitude adaptability crowd, diseases related to depressive disorder, hypertension diseases for pregnancy, liver cancer high-risk crowd and severe chronic obstructive pulmonary at present.
Disclosure of Invention
The invention aims to provide a novel biomarker PRDX2 for auxiliary diagnosis and prognosis prediction of acute kidney injury and a novel approach for diagnosis and prognosis prediction of acute kidney injury.
In order to achieve the above purpose, the invention provides application of a reagent for detecting the expression level of a biomarker PRDX2 in preparing a product for auxiliary diagnosis and prognosis prediction of acute kidney injury.
In a specific embodiment, the acute kidney injury is an acute kidney injury resulting from ischemia reperfusion injury or a cisplatin-induced acute kidney injury.
In a specific embodiment, the product comprises a kit or reagent.
In a specific embodiment, the test sample of the subject is kidney tissue and/or urine.
In a specific embodiment, a subject is diagnosed as at risk of suffering from acute kidney injury when the expression level of PRDX2 in the kidney tissue of the subject is expressed low relative to the expression level of PRDX2 in a normal control or standard.
In a specific embodiment, a subject is diagnosed as at risk of suffering from acute kidney injury when the expression level of PRDX2 in the urine of the subject is expressed high relative to the expression level of PRDX2 in a normal control or standard.
In a specific embodiment, high expression of PRDX2 in urine is positively correlated with tubular injury in a condition associated with acute kidney injury.
It is understood herein that the concentration value of PRDX2 in urine has a correspondence with the degree of tubular injury, i.e., the higher the concentration value of PRDX2 in urine, the more serious the degree of tubular injury.
In the present invention, the biomarker PRDX2 assists in diagnosing acute kidney injury by:
Step 1) collecting a sample of a subject to be tested and a sample of a normal control;
step 2) detecting and comparing the expression quantity of PRDX2 in the sample of the tested subject and the sample of the normal control;
Diagnosing that a subject is at risk of suffering from acute kidney injury when expression level of PRDX2 in kidney tissue of the subject is expressed low relative to expression level of normal control;
and/or
When the expression level of PRDX2 in urine of a subject is expressed high relative to the expression level of PRDX2 in a normal control sample, the subject is diagnosed as being at risk of suffering from acute kidney injury.
Wherein the normal control sample is derived from healthy tissue of a healthy population or a subject to be tested.
The beneficial effects of the invention at least comprise:
1. According to the invention, the differential expression of PRDX2 in an acute kidney injury patient sample is discovered for the first time, so that the PRDX2 can be used as an AKI biomarker for assisting AKI diagnosis or prognosis prediction, and a new way is provided for AKI diagnosis and prognosis prediction.
2. The high expression of PRDX2 in urine is positively correlated with the renal tubular injury in the diseases related to the acute renal injury, so that the expression quantity of PRDX2 in urine can be used as a noninvasive index for reflecting the severity of the acute renal tubular injury, the dependence on invasive renal biopsy diagnosis can be effectively reduced, the urine is convenient to obtain, the PRDX2 can be detected without special treatment, and the detection is rapid and efficient.
Drawings
FIG. 1 shows the identification result of periodic acid-Schiff staining of kidney tissue of ischemia reperfusion Injury (IR) AKI model, wherein a in FIG. 1 is the identification result of periodic acid-Schiff staining of the Sram group, and b in FIG. 1 is the identification result of periodic acid-Schiff staining of the IR group;
FIG. 2 shows the expression of PRDX2 in kidney tissue of IR-AKI mouse model, FIG. 2 (a) shows the Western blotting detection results of the Sham group and the IR group, FIG. 2 (b) shows the PRDX2 immunofluorescence staining result of the Sham group, and FIG. 2 (b) shows the PRDX2 immunofluorescence staining result of the IR group;
FIG. 3 shows the identification result of the periodic acid-Schiff staining of kidney tissue of an AKI model induced by Cisplatin (CP), wherein a in FIG. 3 is the identification result of the periodic acid-Schiff staining of Ctrl group, and b in FIG. 3 is the identification result of the periodic acid-Schiff staining of CP group;
FIG. 4 shows the expression of PRDX2 in kidney tissue of a CP-AKI mouse model, wherein (a) in FIG. 4 is Western blotting detection result of Ctrl group and CP group, a in FIG. 4 (b) is PRDX2 immunofluorescence staining result of Ctrl group, and b in FIG. 4 (b) is PRDX2 immunofluorescence staining result of CP group;
FIG. 5 shows the results of immunofluorescence staining of Acute Tubular Necrosis (ATN) and microscopic lesions without tubular injury (MCD) kidney biopsies PRDX2 and Merge, where a in FIG. 5 shows the result of immunofluorescence staining of PRDX2 in the MCD group, b in FIG. 5 shows the result of immunofluorescence staining of PRDX2 in the ATN group, c in FIG. 5 shows the result of immunofluorescence staining of Merge in the MCD group, and d in FIG. 5 shows the result of immunofluorescence staining of Merge in the ATN group;
FIG. 6 is a quantitative analysis of Acute Tubular Necrosis (ATN) and microscopic lesions without tubular injury (MCD) kidney biopsy PRDX 2;
FIG. 7 is a graph showing the result of correlation analysis based on the expression level of PRDX2 in FIG. 6 and the patient estimated glomerular filtration rate;
FIG. 8 is a graph showing the results of analysis of correlation between the expression level of PRDX2 in FIG. 6 and serum creatinine in patients;
FIG. 9 is a graph showing the detection of NGAL expression in urine from patients with Radical Nephrectomy (RN), 48 hours (PN) after partial nephrectomy, and patients clinically diagnosed with AKI by ELISA;
FIG. 10 shows the detection of PRDX2 expression in urine from patients with Radical Nephrectomy (RN), 48 hours (PN) after partial nephrectomy, and patients clinically diagnosed with AKI by ELISA;
FIG. 11 is a graph showing the detection of KIM 1 expression in urine from patients with Radical Nephrectomy (RN) and patients 48 hours (PN) after partial nephrectomy by ELISA;
FIG. 12 is a correlation analysis result based on the expression level of PRDX2 in FIG. 10 and the expression level of KIM 1 in FIG. 11;
FIG. 13 is a correlation analysis result based on the expression level of PRDX2 in FIG. 10 and the expression level of NGAL in FIG. 9.
Detailed Description
The invention is described in detail below with reference to the drawings and examples, but the invention can be practiced in many different ways, which are limited and covered by the claims.
Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified. Specifically, a polyacrylamide gel (SDS.PAGE) kit is purchased from a Yase company, protease inhibitor cocktail is purchased from Sigma-Aldrich, a BCA detection kit and a protein ladder are purchased from Invitrogen company ;anti-PRDX2 (10545-2-AP)、anti-BAX(50599-2-Ig)、anti-ACTB (66009-1-Ig)、anti-alpha Tubulin (11224-1-AP) and Proteintech, an anti-GPX4 (ab 125066, 1:1000) is purchased from Abcam company, an anti-BCL2 (AF 6139) is purchased from Affinity company, and ELISA detection kits human PRDX2ELISA kit (CSB-EL018654HU)、human KIM1 ELISA kit (CSB-E08807h) 、human NGAL ELISAkit（CSB-E09408h） are all purchased from Huamei biosome.
The specific operation steps of Western blot, immunofluorescence staining, ELISA and HK2 culture and intervention in the invention are as follows:
Western blot
the total protein or cellular protein of the kidney tissue is extracted from the tissue lysate, the protein concentration is measured by BCA method, 30mg of protein is sampled, 10% or 12% polyacrylamide gel electrophoresis (SDS.PAGE) is carried out, 120mAx1.5h wet transfer is carried out on the protein onto PVDF membrane, the sealing solution is sealed for 1h at room temperature, and primary antibody is added for 4 ℃ after TBST elution for incubation overnight. TBST washes the membrane 3 times for 10min each, incubates with the corresponding secondary antibody for 1h at room temperature, and then strips 3 times for 5min each. The antigen and antibody complex is displayed by Enhanced Chemiluminescence (ECL), a darkroom X-ray film is exposed and scanned, and the protein quantification adopts the gray value analysis of a target strip, and the relative expression quantity of the target protein is represented by the gray value of the target strip/the ACTB gray value.
Immunofluorescent staining
Dewaxing and hydrating paraffin kidney tissue section, and then repairing the section in a microwave oven. After 3 times of 1xPBS washing for 5min each, blocking with 5% BSA at room temperature for 1h, incubating anti-PRDX2 (1:200) overnight at 4 ℃, 3 times of 1xPBS washing for 5min each, incubating corresponding fluorescent secondary antibodies, 1h of incubation at room temperature, 3 times of 1xPBS washing, blocking with DAPI blocking tablet, and taking pictures under a fluorescent microscope. Fluorescent positive staining quantification was performed using ImageJ software to quantify the percentage of PRDX2 positive staining area.
ELISA
Subjecting standard substances to gradient dilution and urine dilution (or not), absorbing 100 μl of diluted standard substances or samples into 96-well plates containing corresponding antibodies, incubating at 37deg.C for 2h, discarding liquid without washing, adding 100 μl of biotin-labeled antibody working solution into each well, incubating at 37deg.C for 1h, discarding liquid in the wells, washing for 3 times, spin-drying, adding 100 μl of horseradish peroxidase-labeled avidin working solution into each well, incubating at 37deg.C for 1h, discarding liquid in the wells, washing for 5 times, spin-drying, sequentially adding 90 μl of primer solution into each well, incubating at 37deg.C in dark for 20min, sequentially adding 50 μl of stop solution into each well, terminating reaction, and measuring Optical Density (OD) of each well at 450nm with enzyme-labeled instrument in 5 min. And fitting a standard curve by using the standard measurement value, and calculating the protein expression quantity of each hole sample according to the fitted curve.
HK2 cell culture and intervention
HK2 cells were purchased from ATCC and cultured in a cell incubator at 5% CO 2, 37℃using complete medium (DMEM/F12 medium containing 10% fetal bovine serum and 1% green/streptomycin). If the cells are subjected to anoxic and reoxygenation treatment, the cells are passaged one day before the treatment, the cells grow to about 80% on the next day, the medium is replaced by a sugar-free and serum-free medium (purchased from Gibco corporation), the cells are placed in an anoxic incubator (1%O 2、5% CO2, 37 ℃) for 12 hours, the cells are removed from the anoxic incubator and replaced by a complete medium, and the culture is continued for 12 hours under normal conditions, and then the cells are collected for subsequent analysis.
Example 1
Construction of AKI model and detection of expression of PRDX2 in AKI model kidney tissue
1.1 Construction of IR-AKI mouse model
The IR-AKI mouse model, i.e., acute kidney injury, is caused by renal ischemia reperfusion injury (Ischemia reperfusion injury, IR).
The construction method comprises the steps of injecting pentobarbital (50 mg/kg) into an abdominal cavity of an 8-12-week male C57BL/6 mouse, taking a median incision of the back of the mouse for about 2cm, cutting the abdominal wall layer by layer at the positions of the kidneys at two sides, finding the kidneys and fully exposing the renal pedicles, clamping the renal pedicles by using vascular clamps without damaging blood vessels, taking down the vascular clamps after 30 minutes, recovering the blood supply of the kidneys, and sewing the back incisions layer by layer after receiving the kidneys. Mice were placed on a 37 ℃ thermostat pad during surgery, maintaining the mice body temperature at 36.5±0.3 ℃. Sham (sham) was performed on control mice, i.e., the procedure was identical to that of IR mice except that the renal pedicles were not occluded. After 24 hours, the kidney tissues of the mice in the IR group and the sham control group were collected and respectively identified by Periodic Acid-Schiff (Periodic Acid-SCHIFF STAINING, PAS) staining, and the results are shown in FIG. 1.
Referring to fig. 1, fig. 1 shows the identification result of Periodic Acid-schiff stain (Periodic Acid-SCHIFF STAINING, PAS) of kidney tissue of ischemia reperfusion Injury (IR) AKI model, wherein a in fig. 1 is the identification result of Periodic Acid-schiff stain of Sham group, and b in fig. 1 is the identification result of Periodic Acid-schiff stain of IR group, and it can be seen from fig. 1 that typical kidney tubular injury manifestations such as brush edge shedding, tubular dilation, tubular formation and the like appear in kidney tissue in IR-AKI mouse model, which indicates that IR-AKI mouse model construction is successful.
1.2 Detection of PRDX2 expression in kidney tissue of IR-AKI mouse model
Western blotting and immunofluorescence staining were used to detect PRDX2 expression in kidney tissue of mice in IR group and sham control group, and the results are shown in FIG. 2.
Referring to FIG. 2, FIG. 2 shows the expression of PRDX2 in kidney tissue of IR-AKI mouse model, wherein FIG. 2 (a) shows the Western blotting detection results of the Sham group and the IR group, FIG. 2 (b) shows the immunofluorescence staining result of PRDX2 of the Sham group, and FIG. 2 (b) shows the immunofluorescence staining result of PRDX2 of the IR group, and FIG. 2 (a) shows that the expression of PRDX2 in kidney tissue of IR-AKI mouse model is significantly reduced, and FIG. 2 (b) shows that PRDX2 is mainly expressed in kidney tubular cells and the expression level thereof is significantly reduced in IR-AKI model.
1.3 Construction of CP-AKI mouse model
The CP-AKI mouse model, acute kidney injury, is induced by cisplatin (CISPLATIN, CP).
The construction method specifically comprises the steps of injecting cisplatin (30 mg/kg) into an abdominal cavity of an 8-12-week male C57BL/6 mouse, injecting physiological saline of a corresponding volume into a Control group (Control, ctrl) mouse, collecting kidney tissues in a CP group and the Ctrl group after 48 hours, and performing Periodic Acid-Schiff (Periodic Acid-SCHIFF STAINING, PAS) staining identification, wherein the result is shown in figure 3.
Referring to fig. 3, fig. 3 shows the identification result of Periodic Acid-schiff staining (Periodic Acid-SCHIFF STAINING, PAS) of kidney tissue of cisplatin CP-induced AKI model, wherein a in fig. 3 is the identification result of Periodic Acid-schiff staining of Ctrl group, and b in fig. 3 is the identification result of Periodic Acid-schiff staining of CP group, and it can be seen from fig. 3 that typical kidney tubular damage manifestations such as brush edge shedding, tubular dilation, tubular formation, etc. of kidney tissue appear in CP-AKI mouse model, which indicates successful construction of CP-AKI mouse model.
1.4 Detection of the expression of PRDX2 in kidney tissue of a CP-AKI mouse model
Western blotting and immunofluorescence staining are used to detect the expression of PRDX2 in kidney tissue of mice in CP group and Ctrl control group, and the results are shown in FIG. 4.
Referring to FIG. 4, FIG. 4 shows the expression of PRDX2 in kidney tissue of CP-AKI mouse model, wherein (a) in FIG. 4 is the Western blotting detection result of Ctrl group and CP group, a in FIG. 4 (b) is the immunofluorescence staining result of PRDX2 of Ctrl group, b in FIG. 4 (b) is the immunofluorescence staining result of PRDX2 of CP group, and as can be seen from FIG. 4 (a), the expression of PRDX2 in kidney tissue of CP-AKI mouse model is significantly reduced, and as can be seen from FIG. 4 (b), PRDX2 is mainly expressed in kidney tubular cells and the expression level thereof is significantly reduced in CP-AKI model.
Referring to fig. 1 to 4, it can be seen that in the animal model of acute kidney injury caused by different causes, the expression of PRDX2 in kidney tissue is significantly down-regulated, without damaging the specificity of the cause.
Example 2
Analysis of expression of PRDX2 in kidney tissue of clinical patients and correlation with renal function
Renal tissue specimens (n=6) of patients diagnosed with acute tubular necrosis (acute tubular necrosis, ATN) were collected clinically, their control group was renal tissue specimens (n=6) of patients with microscopic lesions without tubular injury (MINIMALCHANGE DISEASE, MCD) and their clinical data, and expression of PRDX2 in patient's renal tissue was detected using immunofluorescent staining and analyzed for correlation with the patient's estimated glomerular filtration rate, serum creatinine.
TABLE 1 basic information of 12 Kidney puncture biopsy patients and evaluation of glomerular filtration rate and serum creatinine level
The abbreviations in Table 1 are specifically abbreviated as MCD, micro lesions, ATN, acute tubular necrosis, FSGS, focal segmental glomerulosclerosis.
Referring to fig. 5 to 8, wherein fig. 5 shows the results of immunofluorescence staining of Acute Tubular Necrosis (ATN) and micro-lesions without tubular injury (MCD) patient kidney biopsy tissues PRDX2 and mere, wherein a in fig. 5 shows the result of immunofluorescence staining of PRDX2 in MCD group, b in fig. 5 shows the result of immunofluorescence staining of PRDX2 in ATN group, c in fig. 5 shows the result of mere immunofluorescence staining in MCD group, d in fig. 5 shows the result of mere immunofluorescence staining in ATN group, fig. 6 shows the result of quantitative analysis of Acute Tubular Necrosis (ATN) and micro-lesions without tubular injury (MCD) patient kidney biopsy tissues PRDX2, fig. 7 shows the result of correlation analysis based on the expression level of PRDX2 in fig. 6 and the patient estimated glomerular filtration rate, and fig. 8 shows the result of correlation analysis based on the expression level of PRDX2 in fig. 6 and patient serum creatinine.
As can be seen from fig. 5 and 6, PRDX2 was expressed with high positive in the kidney biopsy of patients with microscopic lesions (MCD) whose kidney tissue pathology was manifested as no tubular injury, but PRDX2 positive expression was significantly reduced in the kidney biopsy of patients with Acute Tubular Necrosis (ATN), and its expression was mainly located in tubular cells. The results were similar to the animal test results provided in example 1.
As can be seen from fig. 7 and 8, by performing correlation analysis on the expression of PRDX2 in the kidney tissue of the patient with the kidney function related indexes (estimated glomerular filtration rate and serum creatinine), it was found that there was a significant positive correlation between the expression of PRDX2 in the kidney tissue and the estimated glomerular filtration rate, the correlation coefficient was 0.8631 as shown in fig. 7, and a significant negative correlation between the expression of PRDX2 and the serum creatinine level was-0.5579 as shown in fig. 8. This indicates that the level of expression of PRDX2 in kidney tissue reflects the severity of kidney injury.
Example 3
Analysis of PRDX2 expression in urine of clinical patients and correlation with tubular injury
In the clinical patient performing a Partial Nephrectomy (PN) procedure, vascular clamping of the partially resected side kidney is performed, and renal ischemia is one of the important factors causing tubular injury. The present example incorporated two patients with kidney injury, the first patient was a patient with Partial Nephrectomy (PN) with normal preoperative serum creatinine, single sided kidney ischemia time of 24 min or longer, urine collected 48 hours after surgery (number of samples n=14), the second patient was a patient with clinical diagnosis of AKI with serum creatinine increase of 0.3 mg/dL (26.5. Mu. Mol/L) or ② 1.5 fold increase compared to serum creatinine value in the past 7 days, urine volume reduced to <0.5 mL/kg/hour for at least 6 hours after full fluid resuscitation or urine collected (number of samples n=19).
Control groups were included in patients who underwent radical renal total excision (Radical Nephrectomy, RN) (this procedure had one side of the kidney completely excised, no kidney ischemic injury) and had normal preoperative serum creatinine, and urine was collected 48 hours post-operative (number of samples n=8).
Collected urine was centrifuged at 3000g at 4 ℃ for 10min, urine supernatant was aspirated, and the expression of PRDX2, the expression of the tubular injury markers (NGAL, KIM 1) were detected using an ELISA kit, and further correlation analysis was applied to analyze the correlation of the expression of PRDX2 with tubular injury. The expression results and the correlation analysis results are shown in FIG. 9-FIG. 13.
Referring to fig. 9-11, fig. 9 shows the expression of NGAL in urine of patients with radical renal total excision (RN), 48 hours after partial nephrectomy (Partial Nephrectomy, PN) and clinically diagnosed AKI, fig. 10 shows the expression of PRDX2 in urine of patients with radical renal total excision (RN), 48 hours after Partial Nephrectomy (PN) and clinically diagnosed AKI, and fig. 11 shows the expression of KIM 1 in urine of patients with radical total renal total excision (RN) and 48 hours after Partial Nephrectomy (PN).
As can be seen from fig. 9, the expression level of the tubular injury marker NGAL was significantly increased in urine from patients undergoing Partial Nephrectomy (PN) and patients diagnosed with AKI, compared to Radical Nephrectomy (RN), suggesting the occurrence of tubular injury. As can be seen from fig. 10, the expression level of PRDX2 in urine of PN patients and AKI patients was significantly increased. To further verify the occurrence of tubular injury in PN patients, another classical tubular injury marker, KIM1, was tested in urine and found to significantly increase the expression of PN group KIM1 compared to the control group, as shown in FIG. 11. Fig. 9-11, taken together, demonstrate a significant increase in PRDX2 expression in urine from patients with renal tubular injury.
FIG. 12 is a correlation analysis result based on the expression level of PRDX2 in FIG. 10 and the expression level of KIM1 in FIG. 11, and FIG. 13 is a correlation analysis result based on the expression level of PRDX2 in FIG. 10 and the expression level of NGAL in FIG. 9. From fig. 12 and fig. 13, it can be seen that the expression level of PRDX2 in urine of a patient has a positive correlation with NGAL and KIM1, and the correlation coefficients are 0.705 and 0.7819, respectively, which suggests that the expression level of PRDX2 in urine is closely related to tubular injury.
As is clear from the experimental results of examples 1 to 3, PRDX2 was differentially expressed in kidney tissues of the kidney puncture specimens of ATN patients and the AKI mouse model, and specifically, PRDX2 was significantly expressed in kidney tissues of ATN and AKI, and was closely related to the renal function level, specifically, the expression level was positively related to eGFR and negatively related to serum creatinine level, as compared to the control group, PRDX2 was significantly expressed in urine of AKI patients and kidney partial resection patients, and was positively related to the tubular injury markers KIM-1 and NGAL. The PRDX2 is closely related to the renal tubular injury, can be used as a biomarker of the acute renal injury, is used for assisting in diagnosis or prognosis prediction of the acute renal injury, and provides a new way for diagnosis and prognosis prediction of the acute renal injury.
The foregoing is a further detailed description of the invention in connection with specific preferred embodiments, and is not intended to limit the practice of the invention to such description. It will be apparent to those skilled in the art that several simple deductions and substitutions can be made without departing from the spirit of the invention, and these are considered to be within the scope of the invention.
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| CN114621310A (en) * | 2022-03-18 | 2022-06-14 | 中国药科大学 | Targeted Prdx2 degrader based on triptolide and its preparation method and medical use |
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| JP2011063524A (en) * | 2009-09-15 | 2011-03-31 | Japan Health Science Foundation | Use of peroxiredoxin 2, method for predicting effectiveness of chemotherapy of osteosarcoma, and reagent kit for inspection |
| CN103417961B (en) * | 2012-05-23 | 2018-02-09 | 烟台聚杰生物工程有限公司 | PRDX2 and/or PRDX6 new application |
| EP3358355B1 (en) * | 2017-02-04 | 2023-10-11 | Warszawski Uniwersytet Medyczny | Use of serum 2-cysteine peroxiredoxins (2-cys-prdx) as biomarkers of chronic kidney diseases (ckd) such as lupus nephritis (ln), iga nephropathy (igan) and autosomal-dominant polycystic kidney disease (adpkd) useful for diagnosing, these diseases and method of differentiation of these diseases |
| WO2018228875A1 (en) * | 2017-06-15 | 2018-12-20 | Nestec S.A. | Micro-rna biomarkers of blood-brain barrier dysfunction |
| CN118389662A (en) * | 2024-03-19 | 2024-07-26 | 宁夏医科大学总医院 | Biomarker for effectively distinguishing different types of depressive disorder related diseases and application thereof |
| CN118883940A (en) * | 2024-08-21 | 2024-11-01 | 南京医科大学第二附属医院 | Application of Enolase 1 as a Biomarker for Acute Kidney Injury |
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| CN103025890A (en) * | 2010-04-06 | 2013-04-03 | 卡里斯生命科学卢森堡控股 | Circulating biomarkers for disease |
| CN114621310A (en) * | 2022-03-18 | 2022-06-14 | 中国药科大学 | Targeted Prdx2 degrader based on triptolide and its preparation method and medical use |
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