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亲环素A(CyPA)作为动物模型中早期检测糖尿病肾病的新型生物标志物。

Cyclophilin A (CyPA) as a Novel Biomarker for Early Detection of Diabetic Nephropathy in an Animal Model.

作者信息

El-Ebidi Abdallah Mahmoud, Saleem Tahia H, Saadi Mohamed Gamal El-Din, Mahmoud Hala Abdallah, Mohamed Zeinab, Sherkawy Hoda S

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Aswan University, Aswan, Egypt.

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assuit University, Assuit, Egypt.

出版信息

Diabetes Metab Syndr Obes. 2020 Oct 20;13:3807-3819. doi: 10.2147/DMSO.S260293. eCollection 2020.

DOI:10.2147/DMSO.S260293
PMID:33116728
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7585800/
Abstract

BACKGROUND AND AIM

Type 2 diabetes mellitus (DM) is the most common single cause of the end-stage renal disease (ESRD). Cyclophilin A (CyPA) is an 18-kD protein. The connection between diabetic nephropathy (DN) and the secreted form of CyPA (sCyPA) has been elucidated in this study that aims to investigate sCyPA correlation with renal dysfunction.

MATERIALS AND METHODS

Thirty-four male adult Wistar rats weighing 180-220 g were used. Animals were divided into a study group and a control group, 17 rats in each. Streptozotocin (STZ) and nicotine amide were used to damage some pancreatic cells for induction of type 2 DM. Comparison was made between the study and the control groups. Moreover, a comparison was made between the members of the study group before and after induction of DN.

RESULTS

The rat model that exhibited a higher concentration of urinary sCyPA was detected early in the eighth week. There was a significantly higher level of 24-h urinary CyPA in the study group compared to the control group (-value=0.004) and there was a significant elevation in the 24-h urinary Cyp-A in the study group after injection of STZ compared to the values before injection (-value <0.001). Immunohistochemical analysis of renal tissue revealed that the mean expression of CyPA was higher in the study group than in the control group. For the urinary 24-h CYP-A, using a cutoff of 1.15 ng/mL, the accuracy was 72.4%, sensitivity was (77.8%) and specificity was (67%).

CONCLUSION

According to this animal study, we proved that CyPA is a valuable marker for DN. It is a more sensitive, noninvasive and rapid biomarker for early detection of any renal affection in human diabetic patients.

摘要

背景与目的

2型糖尿病(DM)是终末期肾病(ESRD)最常见的单一病因。亲环素A(CyPA)是一种18kD的蛋白质。本研究阐明了糖尿病肾病(DN)与分泌型CyPA(sCyPA)之间的联系,旨在研究sCyPA与肾功能不全的相关性。

材料与方法

使用34只体重180 - 220g的成年雄性Wistar大鼠。动物被分为研究组和对照组,每组17只。使用链脲佐菌素(STZ)和烟酰胺损伤部分胰腺细胞以诱导2型糖尿病。对研究组和对照组进行比较。此外,对研究组中诱导DN前后的成员进行了比较。

结果

在第8周早期检测到尿sCyPA浓度较高的大鼠模型。研究组24小时尿CyPA水平显著高于对照组(P值 = 0.004),与注射STZ前相比,研究组注射STZ后24小时尿Cyp - A显著升高(P值<0.001)。肾组织免疫组化分析显示,研究组CyPA的平均表达高于对照组。对于尿24小时CYP - A,以1.15 ng/mL为临界值,准确率为72.4%,敏感性为(77.8%),特异性为(67%)。

结论

根据这项动物研究,我们证明CyPA是DN的一个有价值的标志物。它是一种更敏感、无创且快速的生物标志物,可用于早期检测人类糖尿病患者的任何肾脏病变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/ce08973a8b99/DMSO-13-3807-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/f3aabac4617d/DMSO-13-3807-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/dec852043cd2/DMSO-13-3807-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/4250307b30ac/DMSO-13-3807-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/ab1fcff27071/DMSO-13-3807-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/ba105507f999/DMSO-13-3807-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/ce08973a8b99/DMSO-13-3807-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/f3aabac4617d/DMSO-13-3807-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/dec852043cd2/DMSO-13-3807-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/4250307b30ac/DMSO-13-3807-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/ab1fcff27071/DMSO-13-3807-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/ba105507f999/DMSO-13-3807-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a4/7585800/ce08973a8b99/DMSO-13-3807-g0006.jpg

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Cyclohexane extract of walnut leaves improves indices of oxidative stress, total homocysteine and lipids profiles in streptozotocin-induced diabetic rats.核桃叶环己烷提取物可改善链脲佐菌素诱导的糖尿病大鼠的氧化应激指标、总同型半胱氨酸和血脂水平。
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