莪术醇对非酒精性脂肪性肝大鼠肝功能和肝纤维化的影响及机制  

Effects of curcumol on liver function and fibrosis in rats of nonalcoholic fatty liver disease and its mechanism

作　　者：齐书妍[1] 黄华[1] 李永坤[2] 裴林国[1] 张文娟[1] QI Shu-yan;HUANG Hua;LI Yong-kun;PEI Lin-guo;ZHANG Wen-juan(Department of Basic Medicine,Nanyang Medical College,Nanyang 473000;Department of General Surgery,First Affiliated Hospital of Nanyang Medical College,Nanyang 473000,China)

机构地区：[1]南阳医学高等专科学校基础医学部,河南南阳473000 [2]南阳医学高等专科学校第一附属医院普外科,河南南阳473000

出　　处：《中国应用生理学杂志》2021年第6期611-615,672,共6页Chinese Journal of Applied Physiology

基　　金：河南省科技攻关计划(201603256)。

摘　　要：目的:探讨莪术醇(CC)对非酒精性脂肪性肝(NAFLD)大鼠模型肝功能和肝纤维化的影响及机制。方法:采用高脂饮食构建非酒精脂肪肝炎(NASH)伴肝纤维化的大鼠模型,将60只SD大鼠随机分为:空白对照组、模型组(NASH)、NASH+复方鳖甲软肝片(CBT)组(阳性对照组)、NASH+CC组(25、50、100 mg/kg),每组10只。测量大鼠肝脏占体重的百分比,测量大鼠高密度脂蛋白(HDL)、甘油三酯(TG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,HE染色观察肝纤维化情况,免疫组化检测鼠肝组织α-平滑肌肌动蛋白(α-SMA)表达及肝组织核因子κB p65(NF-κB p65)的阳性染色情况,蛋白印迹(Western blot)检测α-SMA、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶抑制剂-1(TIMP-1)蛋白表达及Toll样受体-4(TLR4)、转化生长因子激活激酶-1(TAK1)、NF-κB p65、血管细胞粘附分子-1(VCAM-1)蛋白的表达情况,酶联免疫吸附法(ELISA)检测肝组织中白介素(IL-6、IL-10、IL-1β)、肿瘤坏死因子-α(TNF-α)的表达。结果:与空白对照组相比,模型组大鼠HDL、IL-10含量、MMP-1蛋白表达量显著降低(P<0.05),TG、ALT、AST、肝组织P65阳性率,α-SMA、TIMP-1、TLR4、TAK1、NF-κB p65、VCAM-1表达、IL-6、TNF-α及IL-1β含量显著升高(P<0.05)。与模型组相比,CBT和CC处理后大鼠HDL、IL-10含量、MMP-1蛋白表达量显著升高(P<0.05),TG、ALT、AST、肝组织P65阳性率,α-SMA、TIMP-1、TLR4、TAK1、NF-κB p65、VCAM-1表达、IL-6、TNF-α及IL-1β含量显著降低(P<0.05),其中模型+CC组以高浓度组改善最显著(P<0.05),但各剂量改善幅度均低于模型+CBT组(P<0.05)。结论:莪术醇通过调节TLR4、TAK1、NF-κB p65信号通路,减轻炎症反应,改善肝功能,从而缓解非酒精性脂肪肝肝肝纤维化,且在一定范围内呈浓度依赖性。Objective:To investigate the effects and mechanism of curcumol(CC)on liver function and fibrosis in rats of nonalcoholic fatty liver disease(NAFLD).Methods:The rat models of nonalcoholic steatohepatitis(NASH)combined with liver fibrosis were constructed by high-fat diet.Sixty SD rats were randomly divided into blank control group,model group(NASH),NASH+Compound Biejiarangan Troche(CBT)group(positive control group),and NASH+CC groups(25,50,100 mg/kg),10 rats in each group.The percentage of liver to body weight,and the levels of high density lipoprotein(HDL),triglyceride(TG),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured.The liver fibrosis was observed by HE staining.The expressions ofα-smooth muscle actin(α-SMA)and positive staining of nuclear factorκB p65(NF-κB p65)were detected by immunohistochemistry.The expression levels ofα-SMA,matrix metalloproteinase-1(MMP-1),tissue inhibitor of metalloproteinase-1(TIMP-1)and toll-like receptor-4(TLR4),transforming growth factor-activated kinase-1(TAK1),NF-κB p65 and vascular cell adhesion molecule-1(VCAM-1)were detected by Western blot.The expression levels of interleukin(IL-6,IL-10,IL-1β)and tumor necrosis factor-α(TNF-α)were detected by enzyme linked immunosorbent assay(ELISA).Results:Compared with blank control group,the contents of HDL and IL-10 and the expression level of MMP-1 protein were decreased in model group significantly(P<0.05),while the levels of TG,ALT and AST,the positive rate of P65,α-SMA,TIMP-1,TLR4,TAK1,NF-κB p65,VCAM-1,IL-6,TNF-αand IL-1βwere increased significantly(P<0.05).Compared with model group,the levels of HDL,IL-10 and MMP-1 protein were significantly increased after treatment with CBT and CC(P<0.05),while the levels of TG,ALT,and AST,the positive rate of P65,α-SMA,TIMP-1,TLR4,TAK1,NF-κB p65,VCAM-1,IL-6,TNF-αand IL-1βwere decreased significantly(P<0.05).The improvement in model+high-concentration CC group was the most significant,and which in all concentration groups was lower than that in model+C

关 键 词：非酒精性脂肪性肝 肝纤维化 莪术醇 大鼠 

分 类 号：R243[医药卫生—中医临床基础]