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补骨脂种子提取物通过抑制链脲佐菌素诱导的糖尿病小鼠的肾纤维化和细胞凋亡来减轻糖尿病肾病。

Psoralea corylifolia L. Seed Extract Attenuates Diabetic Nephropathy by Inhibiting Renal Fibrosis and Apoptosis in Streptozotocin-Induced Diabetic Mice.

作者信息

Seo Eunhui, Kang Hwansu, Oh Yoon Sin, Jun Hee-Sook

机构信息

College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, Korea.

Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.

出版信息

Nutrients. 2017 Aug 2;9(8):828. doi: 10.3390/nu9080828.

Abstract

The L. seed (PCS) is a widely used herbal medicine, but its possible effect against diabetic nephropathy has not been studied. To investigate the anti-nephropathic effect of PCS extracts, we performed experiments using a diabetic mouse model and high glucose-treated mesangial cells. Streptozotocin (STZ)-induced diabetic mice were orally administered PCS extract for 8 weeks (500 mg/kg/day). Increased creatinine clearance, urine volume, urine microalbumin, and mesangial expansion were observed in STZ-induced diabetic mice; these were significantly reduced by PCS extract administration. PCS extract significantly reduced fibrosis in the kidney tissue of diabetic mice as evidenced by decreased mRNA expression of collagen type IV-α2, fibronectin, PAI-1, and TGF-β1. In addition, cleaved PARP, an apoptotic gene, was upregulated in the diabetic nephropathy mice, and this was ameliorated after PCS extract treatment. Treatment of high glucose-treated MES-13 cells with isopsoralen and psoralen, major components of PCS extract, also decreased the expression of fibrosis and apoptosis marker genes and increased cell viability. PCS extract exerts protective effects against STZ-induced diabetic nephropathy via anti-fibrotic and anti-apoptotic effects. PCS extract might be a potential pharmacological agent to protect against high glucose-induced renal damage under diabetic conditions.

摘要

光叶菝葜种子(PCS)是一种广泛使用的草药,但尚未对其抗糖尿病肾病的潜在作用进行研究。为了研究PCS提取物的抗肾病作用,我们使用糖尿病小鼠模型和高糖处理的系膜细胞进行了实验。将链脲佐菌素(STZ)诱导的糖尿病小鼠口服给予PCS提取物8周(500毫克/千克/天)。在STZ诱导的糖尿病小鼠中观察到肌酐清除率、尿量、尿微量白蛋白增加以及系膜扩张;给予PCS提取物后这些指标显著降低。PCS提取物显著降低了糖尿病小鼠肾组织中的纤维化,这通过IV型胶原-α2、纤连蛋白、PAI-1和TGF-β1的mRNA表达降低得以证明。此外,凋亡基因裂解型PARP在糖尿病肾病小鼠中上调,而在PCS提取物治疗后得到改善。用PCS提取物的主要成分异补骨脂素和补骨脂素处理高糖处理的MES-13细胞,也降低了纤维化和凋亡标志物基因的表达并提高了细胞活力。PCS提取物通过抗纤维化和抗凋亡作用对STZ诱导的糖尿病肾病发挥保护作用。PCS提取物可能是一种在糖尿病条件下预防高糖诱导的肾损伤的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3f/5579621/733ec3fe7be2/nutrients-09-00828-g001.jpg

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