Jie Ji, Qiang Yu, Weiqi Dai, Liwei Wu, Jiao Feng, Yuanyuan Zheng, Yan Li, Chuanyong Guo
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引用次数: 15
摘要
目的:探讨芹菜素对小鼠肝纤维化的保护作用及其分子机制。方法:采用四氯化碳(CCl4)和胆管结扎(BDL)小鼠纤维化模型，研究芹菜素对肝纤维化的影响。将66只雄性C57小鼠随机分为8组，分别为载药组、CCl4组、CCl4+ l -芹菜素(20 mg/kg)组、CCl4+ h -芹菜素(40 mg/kg)组、假药组、BDL组、BDL+ l -芹菜素(20 mg/kg)组和BDL+ h -芹菜素(40 mg/kg)组。采用qRT-PCR、免疫组化染色、western blotting检测血清肝酶(ALT、AST)、自噬相关蛋白、TGF-β1/Smad3、p38/PPARα通路相关指标。结果:我们的研究证实了芹菜素可以降低ALT和AST的水平，抑制ECM的产生，抑制hsc的活化，调节MMP2和TIMP1的平衡，降低自噬相关蛋白的表达，抑制TGF-β1/Smad3和p38/PPARα通路。结论:芹菜素可能通过TGF-β1/Smad3和p38/PPARα途径抑制肝星状细胞活化和自噬，从而减轻肝纤维化。
Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways.
Objective: The aim of this study is to confirm the hepatocellular protective functions of apigenin and the molecular mechanism on liver fibrosis in mice.
Methods: Carbon tetrachloride (CCl4) and bile duct ligature (BDL) mouse fibrosis models were used to investigate the effects of apigenin on liver fibrosis. Sixty-six male C57 mice were randomly divided into eight groups, including the vehicle group, CCl4 group, CCl4+L-apigenin (20 mg/kg) group, CCl4+H-apigenin (40 mg/kg) group, sham group, BDL group, BDL+L-apigenin(20 mg/kg) group, and BDL+H-apigenin(40 mg/kg) group. Serum liver enzymes (ALT and AST), proteins associated with autophagy, and indicators linked with the TGF-β1/Smad3 and p38/PPARα pathways were detected using qRT-PCR, immunohistochemical staining, and western blotting.
Results: Our findings confirmed that apigenin could decrease the levels of ALT and AST, suppress the generation of ECM, inhibit the activation of HSCs, regulate the balance of MMP2 and TIMP1, reduce the expression of autophagy-linked protein, and restrain the TGF-β1/Smad3 and p38/PPARα pathways.
Conclusion: Apigenin could alleviate liver fibrosis by inhibiting hepatic stellate cell activation and autophagy via TGF-β1/Smad3 and p38/PPARα pathways.
期刊介绍：
PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.
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