加味瓜蒌薤白半夏汤对动静脉内瘘内膜增生的影响  

Effect of added Gualou Xiebai Banxia Decoction on hyperplasia of arteriovenous fistula

作　　者：胥蕾 赵艳龙 曾晓荣 徐新丽 武亦英 XU Lei;ZHAO Yanlong;ZENG Xiaorong(Shanxi Provincial Hospital of Traditional Chinese Medicine,Xi'an Shanxi 710003,China)

机构地区：[1]陕西省中医医院,陕西西安710003

出　　处：《四川中医》2024年第10期34-40,共7页Journal of Sichuan of Traditional Chinese Medicine

基　　金：陕西省中医药管理局项目(编号:SZY-KJCYC-2023-025),陕西省重点研发计划(编号:2020SF-331)。

摘　　要：目的:研究基于血管平滑肌细胞(Vascular smooth muscle cell,VSMC)表型转化机制的加味瓜蒌薤白半夏汤(JWGXB)对动静脉内瘘(Arteriovenous fistula,AVF)内膜增生的影响,为研究中医药防治AVF内膜增生、管腔狭窄提供基础。方法:动物随机分为3组,每组5只,Sham组只取血管组织;AVF组建立颈动脉、颈静脉侧侧吻合的AVF模型;AVF+JWGXB组与AVF组的造模方法相同,给予JWGXB灌胃28天。28天后留取AVF吻合口处静脉段血管组织。HE染色观察AVF吻合口处静脉段血管内膜厚度及病理学改变;免疫组化法及Western blot检测AVF吻合口处静脉段血管组织中的增殖细胞核抗原(PCNA)、平滑肌细胞22α(SM22α)、骨桥蛋白(OPN)表达改变;PCR分析AVF吻合口处静脉段血管组织中炎症因子IL-1β、IL-6 mRNA表达。肾功能衰竭模型采用含腺嘌呤食物饲养法进行诱导肾衰。体外细胞实验,通过培养SPF级新西兰兔胸主动脉段VSMC,建立AngⅡ诱导的VSMC增殖模型,JWGXB含药血清对其进行干预。采用MTT法、流式细胞仪检测VSMC增殖。结果:与Sham组比较,AVF组吻合口血管内膜增生明显,JWGXB干预后,血管内膜增生明显减低(P<0.05)。同时,JWGXB也抑制了AVF组吻合口血管炎症因子IL-1β、IL-6表达(P<0.01)。肾功能衰竭模型下亦是如此。进一步体外、体内增殖研究提示JWGXB可抑制AngⅡ诱导的VSMC增殖和AVF模型的VSMC增殖。表型研究提示,AVF组VSMC的收缩表型标志物SM22α表达降低,合成表型标志物OPN表达增加,而与AVF组比较,AVF+JWGXB组的SM22α表达水平上调,OPN表达降低(P<0.05,P<0.01)。结论:加减瓜蒌薤白半夏汤可通过抑制AVF吻合口处静脉段血管组织中的VSMC增殖、表型转化,减低内膜增生。Objective:To investigate the effects of added Gualou Xiebai Banxia Decoction(JWGXB)on Arteriovenous fistula(AVF)hyperplasia based on the phenotypic transformation mechanism of Vascular smooth muscle cell(VSMC).It provides the basis for studying the prevention and treatment of arteriovenous fistula intimal hyperplasia and lumen stenosis by traditional Chinese medicine.Methods:The animals were randomly divided into three groups,with 5 rabbits in each group:In Sham group,only vascular tissue was taken.The AVF model of carotid artery and jugular vein anastomosis was established in AVF group.The AVF+JWGXB group was modeled by the same method as the AVF group,and JWGXB was given by gavage for 28 days.After 28 days,the vascular tissue of the venous segment at the AVF anastomosis was retained.The intimal thickness and pathological changes of AVF were observed by HE staining.The expression of proliferating cell nuclear antigen(P CNA),smooth muscle cell22α(SM22α)and osteopontin(OPN)were detected by immunohistochemistry and Western blot.The mRNA expression of inflammatory factors IL-1βand IL-6 in the vascular tissue of AVF anastomosis was analyzed by PCR.Renal failure model was induced by adenine-containing food feeding.The proliferation model of VSMC induced by AngⅡwas established through the culture of VSMC in thoracic aorta segment of SPF New Zealand rabbits in vitro,and JWGXB drug-containing serum was applied to it.The proliferation of VSMC was detected by MTT assay and flow cytometry.Results:Compared with Sham group,the anastomotic intimal hyperplasiawas obvious in AVF group,and after JWGXB intervention,the intimal hyperplasia was significantly reduced(P<0.05).Meanwhile,JWGXB also inhibited the expression of vascular inflammatory factors IL-1βand IL-6 in AVF group(P<0.01).The same is true for the renal failure model.Further in vitro and in vivo studies suggest that JWGXB can inhibit AngⅡ-induced VSMC proliferation and AVF model VSMC proliferation.Phenotypic studies indicated that the expression of contractile p

关 键 词：动静脉内瘘 内膜增生 血管平滑肌细胞 表型转化 中医药 

分 类 号：R285.5[医药卫生—中药学]