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益肾安,一种中药方剂,可改善阳离子牛血清白蛋白诱导的大鼠膜性肾小球肾炎。

Yi Shen An, a Chinese traditional prescription, ameliorates membranous glomerulonephritis induced by cationic bovine serum albumin in rats.

机构信息

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, P. R. China.

New Drug R&D Department of Kunming Institute of Kidney Disease, Kunming, P. R. China.

出版信息

Pharm Biol. 2022 Dec;60(1):163-174. doi: 10.1080/13880209.2021.2021947.

Abstract

CONTEXT

Yi Shen An (YSA) is an investigational composite of traditional Chinese medicine (Reference: 2010L000974) for the treatment of renal disease.

OBJECTIVE

To investigate the protective effects of YSA against membranous glomerulonephritis (MGN).

MATERIALS AND METHODS

Male Sprague-Dawley rats were injected with cationic bovine serum albumin (C-BSA) to create a model of MGN. Then, rats were orally treated with YSA at doses of 0.25, 0.5, 1 and 2 g/kg for 35 successive days; prednisone (5 mg/kg) was used as a positive control. At the end of the experimental period, we performed a series of tests, including 24 h urinary protein, and biochemical, immunological, antioxidative, coagulation indices, and histopathological examination.

RESULTS

YSA-1 g/kg significantly lowered urinary protein from 68.37 to 30.74 mg ( < 0.01). Meantime, total protein (TP) and albumin (ALB) recovered from 66.26 and 20.51 g/L to 76.08 and 35.64 g/L ( < 0.01), respectively. YSA removed the deposition of immunoglobulin G (IgG) and complement 3c (C3c), prevented inter-capillary cell hyperplasia on the glomerular basement membrane (GBM), and reduced electron-dense deposits and fusion of podocytes. In addition, serum IgG and superoxide dismutase were significantly elevated. In contrast, malondialdehyde, total cholesterol, triglyceride, circulating immune complex (CIC), and immunoglobulin M decreased in the YSA-treated group. Moreover, the blood coagulation dysfunction was adjusted.

DISCUSSION AND CONCLUSIONS

These findings indicate YSA may exert a therapeutic effect against MGN through the inhibition of CIC formation, and the removal of IgG and C3c deposition from the GBM, thus supporting the development of further clinical trials.

摘要

背景

益肾安(YSA)是一种中药复方制剂(参考文献:2010L000974),用于治疗肾病。

目的

探讨益肾安对膜性肾小球肾炎(MGN)的保护作用。

材料和方法

雄性 Sprague-Dawley 大鼠注射阳离子牛血清白蛋白(C-BSA)建立 MGN 模型。然后,大鼠连续 35 天口服 YSA 剂量为 0.25、0.5、1 和 2g/kg;强的松(5mg/kg)作为阳性对照。实验期末,进行一系列检测,包括 24 小时尿蛋白和生化、免疫、抗氧化、凝血指标及组织病理学检查。

结果

YSA-1g/kg 可显著降低尿蛋白从 68.37 至 30.74mg( <0.01)。同时,总蛋白(TP)和白蛋白(ALB)从 66.26 和 20.51g/L 恢复到 76.08 和 35.64g/L( <0.01)。YSA 清除 IgG 和补体 3c(C3c)在肾小球基底膜(GBM)上的沉积,阻止毛细血管内细胞在 GBM 上增生,减少电子致密沉积物和足细胞融合。此外,血清 IgG 和超氧化物歧化酶明显升高。相反,丙二醛、总胆固醇、甘油三酯、循环免疫复合物(CIC)和免疫球蛋白 M 在 YSA 治疗组中降低。此外,凝血功能障碍得到调整。

讨论与结论

这些发现表明,益肾安可能通过抑制 CIC 形成,以及从 GBM 清除 IgG 和 C3c 沉积,从而发挥治疗 MGN 的作用,支持进一步开展临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932e/8745358/6b8f8bc988e0/IPHB_A_2021947_F0001_B.jpg

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