生地黄特征成分梓醇对肾系膜细胞内质网应激的保护作用研究  

Protective Effects of Catalpol on Endoplasmic Reticulum Stress of Renal Mesangial Cells

作　　者：杜秋[1,2,3] 戴国英 许惠琴[2,3] 陈玉萍 吕高红[2,3] 卢金福 喻斌[2,3] DU Qiu;DAI Guoying;XU Huiqin;CHEN Yuping;LYU Gaohong;LU Jinfu;YU Bin(Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Nanjing 210000,Jiangsu,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,Jiangsu,China;Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,Nanjing 210023,Jiangsu,China;Jinling College,Nanjing University,Nanjing 210000,Jiangsu,China)

机构地区：[1]南京中医药大学附属南京中医院,江苏南京210000 [2]南京中医药大学药学院,江苏南京210023 [3]江苏省中药药效与安全性评价重点实验室,江苏南京210023 [4]南京大学金陵学院,江苏南京210000

出　　处：《中华中医药学刊》2020年第10期101-104,I0032,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金(81874359,81374029,81073111);江苏省高校自然科学基金(17KJB360003);江苏省研究生科研与实践创新计划(KYCX19_1271);南京市卫健委项目(YKK18132)。

摘　　要：目的探讨生地黄特征性成分梓醇对糖基化终末产物(AGEs)刺激肾小球系膜细胞(GMCs)内质网应激的保护作用及其机制。方法GMCs随机分为空白组、模型组、梓醇组(0.1、1.0、10.0μmol·L^-1)、阳性对照物氨基胍组。采用MTS法及流式细胞仪检测梓醇对系膜细胞增殖及细胞周期的影响;Western blotting法检测系膜细胞中内质网应激相关蛋白葡萄糖调节蛋白78(GRP78)、抑制物阻抗性酯酶(IRE1)、X盒结合蛋白1(XBP1),炎症相关因子核转录因子-κB(NF-κB)的表达。结果与模型组相比,梓醇1.0μmol·L^-1、10.0μmol·L^-1均对AGEs致系膜细胞增殖损伤有显著的保护作用(P<0.05或P<0.01);1.0μmol·L^-1的梓醇能明显阻止细胞由G0/G1期进入S期(P<0.01),且能明显减轻内质网的病理损伤;梓醇各剂量组均能使NF-κB蛋白磷酸化减少,GRP78、IRE1的蛋白表达降低,XBP1分化蛋白减少(P<0.05或P<0.01)。结论梓醇可改善AGEs导致的系膜细胞内质网应激,减轻其引起的炎症反应及细胞器损伤,其作用机制与抑制IRE1通路,改善炎症损伤有关。Objective To investigate the protective effect and mechanism of catalpol,a characteristic component of iridoid glycosides,on endoplasmic reticulum stress in glomerular mesangial cells(GMCs)stimulated by advanced glycation end products(AGEs).Methods GMCs were randomly divided into 5 groups,which were blank group,model group,catalpol groups(0.1,1.0,10.0μmol·L^-1),and aminoguanidine group as positive control.The effect of catalpol on GMCs proliferation and cell cycle were detected by MTS assay and flow cytometry.Endoplasmic reticulum stress-related protein:glucose-regulated protein 78(GRP78),inhibitor-resistant ester(IRE1),X-box binding protein 1(XBP1),expression of the inflammation-related factor nuclear transcription factor-κB(NF-κB)were detected by Western blotting.Results Compared with those of the model group,1.0μmol·L^-1 and 10.0μmol·L^-1 catalpol could significantly inhibit the proliferation of GMCs induced by AGEs(P<0.05 or P<0.01),1.0μmol·L^-1 catalpol could obviously prevent cells entering S phase from G0/G1 phase(P<0.01)and reduce the pathological damage of the endoplasmic reticulum.The expressions of endoplasmic reticulum-associated proteins GRP78 and IRE1,the spliced XBP1 protein and the expression of NF-κB phosphorylation could also be decreased by different concentrations of catalpol(P<0.05 or P<0.01).Conclusion Catalpol can improve the endoplasmic reticulum stress,reduce the inflammatory response and organelle damage caused by AGEs.The mechanism was related to the inhibition of IRE1 pathway and the improvement of inflammatory injury.

关 键 词：梓醇 糖基化终末产物 肾小球系膜细胞 内质网应激 IRE1通路 

分 类 号：R285.5[医药卫生—中药学]