黄芪甲苷对高糖诱导的肾小管上皮细胞损伤的保护作用  

Protective Effects of Astragalosides Ⅳ on the Renal Tubular Epithelial Cell Injury Induced by High Glucose

作　　者：徐维佳[1] 牟姗[1] 王琴[1] 施蓓莉[1] 顾乐怡[1] 倪兆慧[1] 

机构地区：[1]上海交通大学医学院附属仁济医院肾内科,上海200127

出　　处：《中国中西医结合肾病杂志》2012年第9期765-769,共5页Chinese Journal of Integrated Traditional and Western Nephrology

摘　　要：目的:旨在探究黄芪甲苷(ASI)对高糖诱导的人肾小管上皮细胞损伤的抑制作用,并阐明其机制。方法:体外培养人肾小管上皮细胞,进行分组:正常对照组:低糖(葡萄糖浓度5.5mmol/L)环境下培养;高糖组:高糖(葡萄糖浓度25mmol/L)环境下培养;ASI各组:分别在高糖培养基内加入不同浓度ASI(包括25、50、100、200μg/ml),在处理后0、1、12、24、48、96h观察,采用TUNEL法和caspase3检测各组细胞凋亡情况,采用ELISA法检测TGF-β1和HGF蛋白含量,采用Western blot检测磷酸化p-38、磷酸化ERK和磷酸化JNK浓度。此外,另在同样高糖培养基内加入p38抑制剂SB202190,1、12、24h观察细胞凋亡情况。最后,取同样高糖环境培养细胞,依次加入HGF50、100、200μg/ml,24h后检测细胞内磷酸化p38蛋白水平。结果:ASI(25～200μg/ml)可抑制高糖诱导的人肾小管上皮细胞凋亡,其抑制作用呈现剂量依赖性与时间依赖性。ASI同样可抑制高糖诱导的TGF-β1蛋白表达和p38MAPK信号通路活性。此外ASI可提高肾小管上皮细胞内HGF浓度;HGF可对p38MAPK信号通路产生抑制作用。结论:ASI抑制高糖诱导的人肾小管上皮细胞凋亡,其机制可能与ASI促进HGF分泌,阻断p38MAPK信号通路,进而抑制细胞凋亡以及TGF-β1的表达有关。ASI可能有助于糖尿病肾病的治疗。Objective： To investigate the inhibition of Astragalosides Ⅳ （ASI） on high glucose - induced human tubular ep- ithelial cell apoptosis. Methods：Tubular epithelial cells were cultured and divided randomly into three groups： Control, High glucose （HG in short）, Astragalosides Ⅳ （with various doses）. The apoptosis of cells was determined using TUNEL staining and caspase3 assay. The protein levels of HGF, TGF - β1 were measured using ELISA. The phospho - p38 production, ERK and JNK were deter- mined using Western blot analysis. Results：ASI with various doses （25 - 200 μ/ml） in our study can alleviate tubular epithelial cell apoptosis induced by high glucose （25 mmol/L）. The effect is shown in dose -dependent and time -dependent manners. ASI can in- hibit the expression of TGF - β1 and the activation of p38 MAPK signaling pathway. It is also shown that ASI increases the production of HGF in human tubular epithelial cells. Conclusion：ASI can inhibit high glucose - induced renal tubular epithelial ceils apoptosis. The mechanism of this action probably involves that ASI blocks p38 signaling pathway, increases HGF secretion, and decrease TGF - β1 expression. It could be a novel approach of treating the diabetic nephropathy.

关 键 词：黄芪甲苷 肝细胞生长因子 细胞凋亡 肾小管上皮细胞 MAPK信号通路 

分 类 号：R692[医药卫生—泌尿科学]