【摘要】 目的探讨miR-350-3p/IL-6介导的STAT3/c-myc信号通路在脂肪性肝纤维化进展中的作用及相关机制。方法20只Balb/c雄性小鼠随机分为正常对照组和HFD+CCl₄组,正常对照组予以普通饮食,HFD+CCl₄组予以高脂高糖饮食并采用腹腔注射2%CCl4油溶液,每周2次,持续5周后处死小鼠,检测血清相关指标,HE及Masson染色观察肝组织形态及纤维化改变,免疫组化检测ki-67表达情况,qRT-PCR检测miR-350-3p、IL-6及肝细胞异常增生相关指标,Western blot检测STAT3/cmyc表达情况。结果与正常对照组比较,HFD+CCl₄组小鼠肝指数增加,血清中ALT与TG含量显著增加;HE及Masson染色显示HFD+CCl₄组小鼠肝脏脂质变性明显,并出现纤维沉积;在m RNA水平上,HFD+CCl₄组中miR-350-3p、IL-6显示良好的负调控关系;肝细胞异常增生相关基因PDGFRb、c-myc、TGF-β、Epcam、CD133、CD44、CD105的表达量明显高于正常对照组;Western blot结果显示,HFD+CCl₄组中p-STAT3及c-myc表达水平较正常对照组明显增加。结论高脂饮食联合CCl₄能够诱导肝脏发生纤维化病变且有肝细胞异常增生,其可能是通过miR-350-3p/IL-6介导的STAT3/c-myc信号通路发挥作用。更多还原

【Abstract】 microRNA plays important roles in regulating metabolic inflammation. Among them, microRNA targets the IL-6/STAT3 signaling pathway, sequentially increases the phosphorylation level of STAT3, which in turn increases the phosphorylation level of STAT3, thereby promoting the occurrence and development of non-alcoholic steatohepatitis. Thus, this study was designed to investigate the role of miR-350-3 p/IL-6-mediated STAT3/c-myc signaling pathway in fatty liver fibrosis and the related mechanisms. Male Balb/c mice were received normal diet（normal group） or high-fat-high-fructose diet（HFD） and intraperitoneal injection of 2% CCl₄ oil solution（HFD+CCl₄ group） twice a week. Five weeks later, the mice were sacrificed and serum-related indicators were detected. HE and Masson staining were used to observe liver tissue morphology and fibrosis changes; immunocytochemistry was used to detect the expression of ki-67; quantitative real-time PCR（qRT-PCR） was used to detect miR-350-3 p, IL-6 and the abnormal proliferation-related genes. Western blot was used to detect the expression of STAT3/c-myc protein. Data showed that the liver index of the mice in the HFD+CCl₄ group was increased significantly and the serum levels of Alanine aminotransferase（ALT） and total triglycerides（TG） increased significantly, as compared with the normal group. Furthermore, the liver of the HFD+CCl₄ group showed significant lipid degeneration and fiber deposition. At the mRNA level, the expression level of miR-350-3 p was decreased, while IL-6 expression increased; the abnormal proliferationrelated genes PDGFRb, c-myc, TGF-β, Epcam, CD133, CD44, and CD105 in the HFD + CCl₄ group were significantly higher than in normal group. Western blot results showed that the expression levels of p-STAT3 and cmyc in HFD+CCl₄ group were significantly higher than in normal group. Taken together, high-fat diet combined with CCl₄ can induce fatty liver fibrosis in hepatocytes, and the mechanism may relates to the miR-350-3 p/IL-6/STAT3/c-myc signaling pathway.更多还原