熊果酸抗肝纤维化作用与AngⅡ/AT1R信号通路的相关性  

Correlation of ursolic acid against liver fibrosis with AngⅡ/AT1R signaling pathway

作　　者：陈涛 刘聪 万思哲 朱萱[2] CHEN Tao;LIU Cong;WAN Si-zhe;ZHU Xuan(Department of Gastroenterology,Fuzhou First People′s Hospital,Jiangxi Province,Fuzhou 344099,China;Department of Gastroenterology,the First Affiliated Hospital of Nanchang University,Jiangxi Province,Nanchang 330006,China)

机构地区：[1]江西省抚州市第一人民医院消化内科,江西抚州344099 [2]南昌大学第一附属医院消化内科,江西南昌330006

出　　处：《中国当代医药》2021年第35期7-11,F0004,共6页China Modern Medicine

基　　金：国家自然科学基金资助项目(81660110);江西省卫生计生委科技计划项目(20197540)。

摘　　要：目的分析熊果酸(UA)发挥抗肝纤维化作用及其与AngⅡ/AT1R信号通路的相关性。方法将40只SD大鼠随机分成对照组、模型组、培哚普利组、UA干预组,每组10只。对照组使用橄榄油灌胃SD大鼠,模型组使用四氯化碳溶液(CCl4)诱导构建SD大鼠肝纤维化模型,培哚普利组和UA干预组在构建SD大鼠肝纤维化模型基础上,分别通过灌胃给予培哚普利和UA。通过HE染色观察肝脏组织病理,天狼星红染色观察肝脏内胶原沉积情况;使用试剂盒检测血清谷草转氨酶、血清谷丙转氨酶、血清总胆红素表达水平;通过蛋白印迹法检测肝脏AngⅡ、AT1R、Ⅰ型胶原蛋白(CollagenⅠ)及α-平滑肌肌动蛋白(α-SMA)蛋白表达量;通过实时荧光定量聚合酶链式反应法检测AngⅡ、AT1R、CollagenⅠ及α-SMA mRNA表达量;通过METAVIR肝纤维化评分系统对肝脏切片进行评分。结果模型组大鼠肝脏的炎细胞浸润程度、气球样变、胶原沉积程度高于对照组大鼠,培哚普利组及UA干预组大鼠肝脏的肝细胞坏死面积、胶原沉积程度低于模型组大鼠;模型组的METAVIR评分高于对照组、培哚普利组和UA干预组,差异有统计学意义(P<0.05);模型组的血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(TBil)水平高于对照组、培哚普利组和UA干预组,差异有统计学意义(P<0.05);模型组的AngⅡ、AT1R、CollagenⅠ及α-SMA蛋白mRNA表达高于对照组、培哚普利组和UA干预组,差异有统计学意义(P<0.05)。结论UA具有抗肝纤维化作用,可显著降低肝脏炎症,减少胶原沉积,显著缓解肝纤维化的进展,其可能与AngⅡ/AT1R信号通路有关。UA有望成为未来针对靶向AngⅡ/AT1R信号通路发挥抗肝纤维化的候选药物。Objective To analyze the anti-fibrotic effect of ursolic acid(UA)and its underlying mechanism based on the AngⅡ/AT1R signaling pathway.Methods Forty SD rats were randomly divided into control group,model group,perindopril group and UA intervention group,with 10 rats in each group.Rats in control group were given olive oil intragastric administration,and rats in model group were induced by carbon tetrachloride solution(CCl4)to construct hepatic fibrosis model,Perindopril group and UA intervention group were given perindopril and UA respectively by intragastric administration on the basis of constructing hepatic fibrosis model of SD rats.Liver histopathology was observed by HE staining,and collagen deposition in liver was observed by Sirius red staining.Serum glutamic-oxalacetic transaminase,glutamic-pyruvic transaminase and serum total bilirubin expression levels were detected using kits.The protein expression levels of AngⅡ,AT1R,CollagenⅠandα-smooth muscle actin(α-SMA)in liver were detected by western blot.The mRNA expression levels of AngⅡ,AT1R,CollagenⅠandα-SMA were detected by real-time fluorescence quantitative polymerase chain reaction.Liver slices were scored by METAVIR hepatic fibrosis scoring system.Results The degree of inflammatory cell infiltration,balloon-like change and collagen deposition of liver in model group were higher than those in control group,the necrosis area of liver cells in the perindopril group and UA intervention group was lower than that in the model group.METAVIR score in model group was higher than that in control group,Perindopril group and UA intervention group,the differences were statistically significant(P<0.05).The expression levels of serum aspartate aminotransferase(AST),alanine aminotransferase(ALT)and total bilirubin(TBil)in model group were higher than those in control group,Perindopril group and UA intervention group,the differences were statistically significant(P<0.05).The expressions of AngⅡ,AT1R,CollagenⅠandα-SMA proteins in liver of model group we

关 键 词：AngⅡ AT1R 培哚普利 熊果酸 肝纤维化 

分 类 号：R965[医药卫生—药理学]