大黄[庶虫]虫丸调控ASIC1a/VEGF通路缓解肝纤维化  

Dahuang zhechong pills regulate ASIC1a/VEGF pathway and alleviate hepatic fibrosis

作　　者：曹锐 朱月琴 林慧敏 李洋洋[1,2,3] 闻祥瑞 莫文汐 程欣然 吴丽 黄艳[1,2,3] CAO Rui;ZHU Yue-qin;LIN Hui-min;LI Yang-yang;WEN Xiang-rui;MO Wen-xi;CHENG Xin-ran;WU Li;HUANG Yan(School of Pharmacy,Anhui Medical University,Hefei 230032,China;Anhui Province Key Laboratory of Major Autoimmune Diseases,Anhui Medical University,Hefei 230032,China;Inflammation and Immune Mediated Diseases Laboratory of Anhui Province,Anhui Medical University,Hefei 230032,China;Dept of Pharmacy,West Branch of the First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Cancer Hospital),Hefei 230002,China;Dept of Pharmacology,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]安徽医科大学药学院,安徽合肥230032 [2]安徽医科大学重大自身免疫性疾病安徽省重点实验室,安徽合肥230032 [3]安徽医科大学炎症免疫性疾病安徽省实验室,安徽合肥230032 [4]中国科学技术大学附属第一医院(安徽省立医院)药剂科,安徽合肥230002 [5]南京中医药大学药学院,江苏南京210023

出　　处：《中国药理学通报》2022年第6期928-934,共7页Chinese Pharmacological Bulletin

基　　金：炎症免疫性疾病安徽省实验室开放基金项目(IMMDL202009);2021年度高校学科(专业)拔尖人才学术资助项目(No gxbjZD2021048);2021年国家级大学生创业创新计划项目(No 202110366040);安徽医科大学基础与临床合作研究提升计划项目(2019xkjT015)。

摘　　要：目的探究中药复方大黄[庶虫]虫丸(DHZCP)对四氯化碳(CCl_(4))诱导的大鼠化学性肝纤维化模型的防治作用及酸敏感离子通道1a(acid-sensitive ion channels 1a,ASIC1a)/血管内皮生长因子(vascular endothelial growth factor,VEGF)相关机制。方法采用大鼠腹腔注射CCl_(4)植物油混合溶液建立肝纤维化模型。随机均分成六组:对照组、肝纤维化模型组、DHZCP低剂量组、DHZCP中剂量组、DHZCP高剂量组和秋水仙碱(Col)阳性对照组。HE染色、血清学指标评测各组肝脏病理损伤,Masson染色法观察各组胶原纤维的生成,免疫组化、Western blot、q-PCR法检测各组肝组织中ASIC1a、CaMKKβ、VEGF、α-SMA、Collagen-Ⅰ相关蛋白的表达水平。结果模型组大鼠血清ALT、AST水平明显升高,肝组织结构损坏严重,ASIC1a、CaMKKβ、VEGF、α-SMA、Collagen-I基因和蛋白表达水平明显上升。与模型组相比DHZCP各治疗组可明显缓解CCl4所致的大鼠肝纤维化病理变化,明显降低血清ALT、AST水平,剂量依赖性下调ASIC1a、CaMKKβ、VEGF、α-SMA、Collagen-Ⅰ等基因和蛋白表达水平。结论DHZCP可改善大鼠肝纤维化病变,其作用机制可能与调节肝组织中ASIC1a/VEGF表达有关。Aim To examine the therapeutic effects of DHZCP on carbon tetrachloride(CCl_(4))-induced chemical hepatic fibrosis model in rats and the mechanism of acid-sensitive ion channels 1a(ASIC1a)and vascular endothelial growth factor(VEGF)-related mechanisms.Methods The rats were injected intraperitoneally with CCl_(4) vegetable oil mixture to establish hepatic fibrosis model,and randomly divided into six groups:control group,hepatic fibrosis model group,DHZCP low dose group,DHZCP medium dose group,DHZCP high dose group and colchicine(Col)positive control group.HE staining was used to observe the pathological changes of hepatic structures in each group,Masson staining to view the production of collagen fibers in each group,and immunohistochemistry,Western blot,q-PCR to investigate the expression level of ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I proteins.Results In model group,serum ALT and AST levels were obviously up-regulated,liver tissue structure was severely damaged,and ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I gene and protein expression levels were significantly elevated.Compared with model group,each treatment group of DHZCP could markedly alleviate the pathological changes of liver fibrosis caused by CCl_(4),significantly reduce the serum ALT and AST levels,and dose-dependently down-regulate the gene and protein expression levels of ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-Ⅰ,etc.Conclusions DHZCP ameliorates hepatic fibrosis in rats,and its mechanism of action may be associated with the regulation of ASIC1a/VEGF.

关 键 词：大黄[庶虫]虫丸 肝纤维化 酸敏感离子通道 四氯化碳 Α-SMA VEGF 

分 类 号：R-332[医药卫生] R289.5