[关键词]
[摘要]
本文研究了木瓜提取物对小鼠脂肪肝的干预作用。将40只雄性昆明小鼠随机分成4组,正常组、高脂组和药物低(100 mg/kg)、高(300 mg/kg)剂量组。正常组给予普通饲料,高脂组给予高脂高糖饲料,用药组采用木瓜提取物低、高剂量饲料喂养,1月后处死,检测小鼠血清相关指标,HE染色观察肝脏组织形态,RT-PCR和激光共聚焦显微镜(Confocal)检测脂代谢相关基因表达,qPCR检测miR-199a-5p水平。与正常组相比,高脂组小鼠血清中TC、ALT的水平增高;组织病理结果显示,肝脏脂肪变性明显;RT-PCR和Confocal结果显示,HGF、VEGFa和c-Met的表达降低,qPCR显示,高脂组中miR-199a-5p水平增高。与高脂组比较,药物低、高剂量组脂肪肝病理损伤明显改善,血清ALT、TC含量均下降,HGF、VEGFa和c-Met表达水平上调,miR-199a-5p水平降低。因此木瓜提取物对高脂高糖诱导的小鼠脂肪肝有保护作用,其可能的机制是通过调节miR-199a-5p-HGF/c-Met信号通路发挥作用。
[Key word]
[Abstract]
The protective effects of active components extracted from Chaenomeles Speciosa (EACCS) on non-alcoholic fatty liver disease (NAFLD) in mice were investigated. Forty male KM mice were equally randomized into four groups, namely, normal group, model group, low-dose EACCS group (100 mg/kg body weight/day), and high-dose EACCS group (300 mg/kg body weight/day). The normal group was fed with a normal diet, the model group was given a high-fat–high-fructose diet (HFFD), and the low-dose and high-dose EACCS groups were given HFFD followed by EACCS at low- and high-dose, respectively. Body weights were monitored. The mice were sacrificed 1 month later and serum-based biomarkers and morphology of liver tissue were examined. Real-time (RT)-PCR and confocal microscopy techniques were used to detect the expression of lipid metabolism-related genes. Compared with the normal group, the serum alanine aminotransferase (ALT) and total cholesterol (TC) of the model group increased, indicating significant steatosis; The expression levels of hepatocyte growth factor (HGF), vascular endothelial growth factor-A (VEGF-A) and c-Met also decreased in the model group, whilst the expression level of miR-199a-5p increased. Compared with the model group, the hepatic lipid accumulation of EACCS groups was obviously suppressed with significantly decreased serum ALT and TC levels and the expression levels of hepatic HGF, VEGFa and c-Met mRNA increased; and the expression levels of miR-199a-5p increased. Therefore, EACCS has protective effects on NAFLD mice induced by HFFD, and its mechanism may be related to the activation of miR-199a-5p-HGF/c-Met signaling pathway in the liver tissues.
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[基金项目]
国家自然科学基金项目(81473461)