黄芪通过阻断内质网应激改善糖尿病肾病大鼠蛋白尿的研究

Huangqi(Astragalus membranaceus)Attenuates Proteinuria in Streptozotocin-Induced Diabetic Nephropathy Through Inhibition Endoplasmic Reticulum Stress

目的探讨黄芪对链脲佐菌素(STZ)诱导的糖尿病肾病(DN)大鼠蛋白尿的作用及分子机制。方法将雄性SD大鼠随机分为正常对照组(Normal)、糖尿病肾病组(Model)、黄芪治疗组(AS-M)和苯丁酸组(PBA),每组6只,在治疗第8周末检测各组大鼠肾质量指数(KI)、24 h尿蛋白排泄率(UAER)、血肌酐(Scr)、尿素氮(SUN);观察肾脏病理改变;检测肾组织eIF2α、PERK和JNK磷酸化水平,测定GRP78和ORP150蛋白及mRNA的表达变化。结果与正常组大鼠比较,模型组大鼠KI显著增高,UAER显著增加;病理显示DN大鼠肾小球系膜基质积聚;肾组织eIF2α、PERK及JNK磷酸化水平显著上调,GRP78和ORP150蛋白及基因表达明显升高。与模型组大鼠比较,AS-M大鼠KI和UAER显著降低;肾小球系膜基质积聚等病理变化显著改善;大鼠肾组织eIF2α、PERK和JNK磷酸化水平明显降低,GRP78和ORP150表达明显下调。结论黄芪能显著减少糖尿病肾病大鼠蛋白尿,改善糖尿病大鼠肾脏病理变化,这种效应与黄芪抑制肾组织内质网应激有关。

Objective To investigate the effect and mechanism of Huangqi(Astragalus membranaceus)(AS-M)on proteinuria of diabetes rats induced with streptozotocin(STZ).Methods Male SD rats were randomly divided into four groups:normal control group(Normal group),diabetic nephropathy group(Model group),diabetic nephropathy plus AS-M treatment group(AS-M group)and diabetic nephropathy plus 4-PBA treatment group(PBA group).At the end of 8 weeks,serum creatinine(Scr),blood urea nitrogen(BUN)and 24 hour urinary protein excretion rate(UAER)were detected by HITACHI automatically.The morphology of kidney was examined by special staining of histological evaluation(HE).The total and phosphorylation of eIF2α,PERK and JNK were determined by Western blotting,whereas expressions of mRNA or protein for GRP78 and ORP150 were determined by real-time PCR or Western blotting separately.Results AS-M treatment significantly reduced the urinary albumin excretion,plasma creatinine and blood urea nitrogen,prevent the glomerular pathological alteration induced by STZ.AS-IV treatment significantly prevented the phosphorylation of eIF2α,PERK and JNK and inhibited the expressions of GRP78 and ORP150 markedly.Conclusion AS-M treatment significantly reduced proteinuria and renal pathogenesis of rats with diabetes through inhibition of endoplasmic reticulum stress.