白术内酯Ⅲ调节Hippo/YAP信号通路对非酒精性脂肪肝大鼠肝纤维化的影响  

Effect of AtractylenolideⅢon liver fibrosis in rats with non-alcoholic fatty liver disease by regulating the Hippo/YAP signaling pathway

作　　者：姚硕 李源 段超 曾艳[2] YAO Shuo;LI Yuan;DUAN Cha(Department of Integrated Traditional Chinese and Western Medicine,Liyuan Hospital of Tongji Medical College of Huazhong University of Science&Technology,Hubei,Wuhan 430077,China)

机构地区：[1]华中科技大学同济医学院附属梨园医院中西医结合科,武汉市430077 [2]华中科技大学同济医学院附属梨园医院血液科,武汉市430077

出　　处：《河北医药》2024年第21期3212-3216,3221,共6页Hebei Medical Journal

基　　金：湖北省中医药科研立项项目(编号:ZY2023F036)。

摘　　要：目的探讨白术内酯Ⅲ(ATLⅢ)调节河马(Hippo)/yes-相关蛋白(YAP)信号通路对非酒精性脂肪肝(NAFLD)大鼠肝纤维化的影响。方法SPF级SD大鼠36只按照随机数字表法分为control组、NAFLD组、ATLⅢ低、中、高剂量组、阳性对照组(复方鳖甲软肝片),每组6只,除control组外采用高脂饮食构建NAFLD大鼠,灌胃或尾静脉注射相应药物,1次/d,连续4周,检测大鼠血脂及肝功能指标天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT);酶联免疫吸附(ELISA)检测血清透明质酸(HA)、层粘连蛋白(LN)纤维化指标;HE染色观察肝脏组织病理改变并进行NAFLD活动度评分(NAS);Masson染色观察大鼠肝脏组织纤维化情况;免疫组化法检测α-平滑肌肌动蛋白(α-SMA)表达;Western blot检测肝组织中转化生长因子-β1(TGF-β1)及Hippo-YAP信号通路蛋白表达。结果与control组比较,NAFLD组大鼠TC、TG、LDL-C水平、HA、LN、AST、ALT、NAS评分及α-SMA、TGF-β1、TAZ表达水平显著升高,HDL-C水平、p-LATS1/LATS1、p-YAP/YAP表达显著降低(P<0.05);与NAFLD组比较,ATLⅢ低、中、高剂量组及阳性对照组大鼠TC、TG、LDL-C、HA、LN、AST、ALT、NAS评分及α-SMA、TGF-β1、TAZ表达水平显著降低,HDL-C水平、p-L ATS1/LATS1、p-YAP/YAP表达显著升高(P<0.05)。结论ATLⅢ可能通过抑制Hippo/YAP信号通路的激活,改善NAFLD大鼠肝纤维化。Objective To investigate the effect of AtractylenolideⅢ(ATLⅢ)on liver fibrosis in rats with non-alcoholic fatty liver disease(NAFLD)by regulating the Hippo/yes-associated protein(YAP)signaling pathway.Methods Sprague-Dawley(SD)rats in the specific-pathogen free(SPF)grade were randomly grouped into control group,NAFLD group,low-dose ATLⅢgroup,medium-dose ATLⅢgroup,high-dose ATLⅢgroup,and positive control group(Compound Biejia Ruangan tablets)using a random number table.Except for rats in the control group,NAFLD modeling was constructed by feeding a high-fat diet in the remaining rats.Drugs were administered by gavage or tail vein injection once a day for 4 consecutive weeks.Blood lipids and liver function indicators(alanine aminotransferase[AST]and aspartate aminotransferase[ALT])were detected.Serum levels of fibrosis indicators like hyaluronic acid(HA)and laminin(LN)were measured by Enzyme-linked immunosorbent assay(ELISA).Hematoxylin and eosin(H&E)staining was applied to observe pathological changes in rat liver tissues and the NAFLD activity score(NAS)was calculated.Masson staining was applied to observe liver fibrosis.Positive expression ofα-smooth muscle actin(α-SMA)was detected by immunohistochemical staining.Western blot was applied to detect protein expressions of transforming growth factor-β1(TGF-β1)and proteins in the Hippo-YAP signaling pathway in rat liver tissue.Results Compared with those of the control group,rats in the NAFLD group presented significantly higher total cholesterol(TC),triglyceride(TG),low-density lipoprotein-cholesterol(LDL-C),HA,LN,AST,ALT,NAS and expression levels ofα-SMA,TGF-β1 and transcriptional co-activator with PDZ-binding motif(TAZ),but significantly lower high-density lipoprotein-cholesterol(HDL-C),p-LATS1/LATS1 and p-YAP/YAP(P<0.05).Compared with rats in the NAFLD group,rats in the low-dose ATLⅢgroup,medium-dose ATLⅢgroup,high-dose ATLⅢgroup and positive control group presented significantly lower TC,TG,LDL-C,HA,LN,AST,ALT,NAS and expression levels of�

关 键 词：白术内酯Ⅲ 河马/yes-相关蛋白 非酒精性脂肪肝 肝纤维化 

分 类 号：R349.31[医药卫生—基础医学]