黄芪甲苷对STZ诱导的糖尿病大鼠肾组织内质网应激及CHOP信号通道的影响  

Influence of astragalosideⅣon endoplasmic reticulum stress and CHOP signaling pathways in diabetic nephropathy rats induced with STZ

作　　者：刘红[1] 王增四[1] 高文[2] 何达[1] 谢小行[1] LIU Hong;WANG Zeng-si;GAO Wen;HE Da;XIE Xiao-hang(Wuhan Hospital of Integrated Chinese&Western Medicine,Hubei Wuhan 430022,China;Affiliated Tongji Hospital,Tongji Medical College,Huazhong University of Science&Technology,Hubei Wuhan 430030,China)

机构地区：[1]武汉市中西医结合医院肾病内科,湖北武汉430022 [2]华中科技大学同济医学院附属同济医院,湖北武汉430030

出　　处：《中国医院药学杂志》2021年第13期1318-1322,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金资助项目(编号:81503432);湖北省自然科学基金资助项目(编号:2015CFB395);湖北省卫生健康委员会中医药科研项目(编号:ZY2019Q024)。

摘　　要：目的:通过观察黄芪甲苷对链脲佐菌素(STZ)诱导的糖尿病肾病(DN)大鼠肾组织内质网应激标志蛋白及CHOP信号通路表达的影响,探讨黄芪甲苷延缓早期DN进展的作用机制。方法:采用STZ诱导糖尿病肾病大鼠为动物模型,随机分为模型组(model)、黄芪甲苷组(AS-IV)、苯丁酸组(PBA),每组6只,并以6只雄性SD大鼠作为正常组(normal)。在治疗第8周末检测各组大鼠24 h尿蛋白排泄率(UAER)、血肌酐(SCR)、尿素氮(BUN)、肾质量指数(KI);HE和PAS观察肾脏病理改变;流式细胞术检测各组大鼠肾细胞凋亡情况;Western blot检测肾组织eIF2α、PERK和IREα磷酸化水平,并测定GRP78、CHOP、BAX、BCL2和Cleaved caspase-3蛋白的表达变化。结果:与正常组比较,模型组大鼠肾小球UAER明显升高,肾功能恶化,肾脏病理检查示系膜基质积聚,肾组织细胞凋亡水平提高;肾组织eIF2α、PERK及IREα磷酸化水平显著上调,GRP78、CHOP和Cleaved caspase-3表达明显升高,BAX/BCL-2升高。与模型组大鼠比较,黄芪甲苷组大鼠KI和UAER显著降低,肾功能改善,肾小球系膜基质积聚等病理变化显著减轻,肾组织细胞凋亡率显著降低;肾组织eIF2α、PERK和IREα磷酸化水平明显降低,GRP78、CHOP和Cleaved caspase-3表达明显下调,BAX/BCL-2下降。结论:黄芪甲苷能显著减少糖尿病肾病大鼠蛋白尿,改善大鼠肾脏组织病理损伤,这种效应与黄芪甲苷显著抑制肾组织内质网应激、缓解CHOP介导的肾组织细胞过度凋亡有关。OBJECTIVE To explore the renoprotective effects and molecular of astragaloside IV(AS-IV)in diabetic rats induced with streptozotocin(STZ).METHODS Male Sprague-Dawley(SD)rats were divided into four groups of normal control(normal),diabetic nephropathy(model),diabetic nephropathy plus AS-IV treatment(AS-IV)and diabetic nephropathy plus PBA treatment(PBA).At Week 8,serum creatinine(SCR),urea nitrogen(BUN)and 24 hour urinary protein excretion rate(UAER)were detected by HITACHI automatically,renal morphology was examined after stains of hematoxylin&eosin(HE)and periodic acid-Schiff(PAS)and apoptosis of renal cells was detected by flow cytometry.The signaling pathways in UPR of phosphorylation of eIF2α,PERK and IRE1α,the apoptotic related factors including CHOP,BAX,BCL-2 and Cleaved caspase-3 were determined by Western blot.RESULTS As compared with normal group,model group showed a marked elevation of UAER,worsening of renal function,greater mesangial matrix expansion and higher apoptotic rate of renal cells;the phosphorylations of eIF2α,PERK and IRE1αwere enhanced,the expressions of GRP78,CHOP and Cleaved caspase-3 increased significantly and BAX/BCL-2 became up-regulated.AS-IV treatment could significantly suppress the elevation of UAER,improve glomerular pathologies,lower the apoptotic rate of renal cells,reduce the phosphorylations of IRE1α,PERK and eIF2α,blunt the expressions of GRP78,CHOP and Cleaved caspase-3 and suppressed BAX/BCL-2 significantly.CONCLUSION AS-IV treatment may improve renal pathologies of diabetic rats through removing endoplasmic reticulum stress and suppressing renal cell apoptosis.

关 键 词：黄芪甲苷 凋亡 糖尿病肾病 内质网应激 

分 类 号：R285.5[医药卫生—中药学]