摘要
目的 研究健脾益气方通过干预腹膜透析(PD)大鼠内质网应激IRE1α-XBP1通路,诱导自噬以减轻腹膜间皮细胞(PMC)上皮间充质转化(EMT)的作用及机制。方法 SD大鼠72只,采用5/6肾切除联合腹膜透析液制备腹膜纤维化(PF)模型,随机分为假手术组、模型组、西药组、中药高、中、低剂量组,每组12只,进行28 d药物干预。苏木素-伊红(HE)染色观察腹膜组织形态学改变,免疫组化、Western印迹及RT-聚合酶链反应(PCR)测定IRE1α-XBP1通路自噬及纤维化标志蛋白表达。结果 与模型组比较,假手术组、西药组、中药高、中、低剂量组葡萄糖调节蛋白(GRP)78、XBP1s、微管相关蛋白1轻链(LC)3-Ⅱ、自噬相关蛋白Beclin-1、E-钙黏蛋白(cadherin)、α-肌动蛋白(SMA) mRNA及蛋白、pIRE1α蛋白表达差异均有统计学意义(P<0.05)。结论 健脾益气方能够通过干预内质网应激通路IRE1α-XBP1诱导PMC自噬,激活其适应性保护作用,达到减轻PMC的EMT、改善腹膜功能,最终起到拮抗PF作用。
Objective To study the effect and mechanism of Jianpi Yiqi Recipe on reducing epithelial-mesenchymal transition(EMT)of peritoneal mesothelial cells(PMC)by intervening in IRE1α-XBP1 pathway of endoplasmic reticulum stress in peritoneal dialysis(PD)rats.Methods A total of 72 SD rats were used to prepare peritoneal fibrosis(PF)model by 5/6 nephrectomy combined with peritoneal dialysis solution.They were randomly divided into sham operation,model,western medicine groups,high,medium and low dose groups of traditional Chinese medicine groups,with 12 rats in each group,for 28 d of drug intervention.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of peritoneal tissue.Immunohistochemistry,Western blot and RT-polymerase chain reaction(PCR)were used to determine the expression of autophagy and fibrosis marker proteins in IRE1α-XBP1 pathway.Results Compared with model group,the expressions of glucose regulated protein(GRP)78,XBP1s,microtubule-associated protein light chain(LC)3-Ⅱ,autophagy associated protein Beclin-1,E-cadherin,α-smooth muscle actin(SMA)mRNA and protein,PIRE1αprotein in sham operation group,western medicine group,high,medium and low dose groups of traditional Chinese medicine groups had statistically significant difference(P<0.05).Conclusions Jianpi Yiqi Recipe could induce autophagy of PMC by interfering with endoplasmic reticulum stress pathway IRE1α-XBP1,activate its adaptive protection,reduce EMT of PMC,improve peritoneal function,and ultimately play an antagonistic role in PF.
作者
刘前程
刘鑫
邓湘雨
周成涵
钟文露
史伟
孟立锋
LIU Qian-Cheng;LIU Xin;DENG Xiang-Yu(Guangxi University of Traditional Chinese Medicine,Nanning 530023,Guangxi,China)
出处
《中国老年学杂志》
CAS
北大核心
2024年第7期1642-1647,共6页
Chinese Journal of Gerontology
基金
国家自然科学基金(81860838)
广西自然科学基金面上项目(2020JJA140292)
第五批全国中医临床优秀人才研修项目(国中医药人教函1号)
桂派杏林拔尖人才(桂中医大202223)
广西中医药大学第一附属医院青年拔尖人才(院2022年46号)
广西中医药适宜技术开发与推广项目(GZSY21-25,GZSY22-25)
广西研究生教育创新计划项目(xjyb056)。
