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中国应用生理学杂志 ›› 2021, Vol. 37 ›› Issue (6): 611-615.doi: 10.12047/j.cjap.6058.2021.082

• 研究论文 • 上一篇    下一篇

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*

齐书妍1△, 黄华1, 李永坤2, 裴林国1, 张文娟1   

  1. 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
  • 收稿日期:2020-03-30 修回日期:2021-02-05 出版日期:2021-11-28 发布日期:2021-11-25
  • 通讯作者: Tel:18736500959; E-mail: qsy202001@163.com
  • 基金资助:
    *河南省科技攻关计划(201603256)

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

QI Shu-yan1△, HUANG Hua1, LI Yong-kun2, PEI Lin-guo1, ZHANG Wen-juan1   

  1. 1. Department of Basic Medicine, Nanyang Medical College, Nanyang 473000;
    2. Department of General Surgery, First Affiliated Hospital of Nanyang Medical College, Nanyang 473000, China
  • Received:2020-03-30 Revised:2021-02-05 Online:2021-11-28 Published:2021-11-25

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。

关键词: 非酒精性脂肪性肝, 肝纤维化, 莪术醇, 大鼠

Abstract: 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 of α-smooth muscle actin (α-SMA) and positive staining of nuclear factor κB p65 (NF-κB p65) were detected by immunohistochemistry. The expression levels of α-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-α and IL-1β were 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-α and IL-1β were 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+CBT group (P<0.05). Conclusion: CC can reduce inflammation response and improve liver function by regulating TLR4, TAK1 and NF-κB/p65 signaling pathway, and thus alleviating liver fibrosis, showing concentration-dependence within certain range.

Key words: nonalcoholic fatty liver disease, liver fibrosis, curcumol, rat

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