竹节参总皂苷通过调节miR-34a/PPARα干预小鼠脂肪肝的作用研究

Protective Effects of Panax japonicus Saponins on Non-alcoholic Fatty Liver Disease through MiR-34a and PPARα Expression Regulation

摘要:

本文研究了竹节参总皂苷对小鼠脂肪肝的干预作用。应用高糖高脂饲料制备脂肪肝模型，同时采用灌胃的方法给予竹节参低剂量（50 mg/kg）和高剂量（100 mg/kg）处理，检测血清和肝脏中的相关指标，HE和油红O染色来检测小鼠肝脏组织病理学变化，进一步用Real-Time PCR检测肝组织miRNA及相关基因的转录水平，Western Blotting检测PPARα的表达情况。结果显示模型组的小鼠血清ALT的水平，肝脏组织的TG均高于正常组；HE和油红O染色发现模型组肝组织表现为脂肪样变，脂质明显沉积，提示脂肪肝模型成立。Real-Time PCR和Western Blotting检测，模型组的miR-34a、SREBP-1c和FASN的表达较正常组升高，而PPARα表达降低。与模型组相比，经过竹节参药物的干预后肝脏组织病理学变化明显改善，脂质沉积减少；ALT水平降低。因此竹节参总皂苷可能通过miR-34a靶向PPARα的信号通路发挥对小鼠脂肪肝的干预作用，这一发现为脂肪肝的预防与治疗提供有效参考。

Abstract:

The protective effects of total saponins from Panax japonicus (TSPJ) on non-alcoholic fatty liver disease (NAFLD) in mice were investigated. A mouse model of NAFLD was established by feeding a high-fat, high-fructose diet, with simultaneous gavage administration of TSPJ (50 mg/kg and 100 mg/kg) to the TSPJ group for 3 weeks. Serum- and liver-related indicators were monitored; histopathologic changes in liver were observed using hematoxylin-eosin (HE) and oil red O staining. Real-time polymerase chain reaction (RT-PCR) and western blotting were utilized for the detection of transcriptional levels of miRNA and related genes in liver tissue and the expression level of peroxisome proliferator-activated receptor (PPAR) α, respectively. The levels of serum alanine aminotransferase (ALT) and liver triglyceride (TG) in the model group were higher than those in the normal group. HE staining and oil red O staining showed fatty degeneration and fat deposition in the liver tissue, suggesting that a successful NAFLD model had been established. The results of RT-PCR and western blot analysis revealed that the expression levels of microRNA (miR)-34a, sterol regulatory element binding protein (SREBP)-1c, and fatty acid synthase (FASN) were significantly increased. Compared with the fatty liver group, the TSPJ treatment group showed significantly improved histopathologic changes in liver, reduced fat deposition, and reduced ALT levels. Therefore, intervention of the total saponins of Panax japonicus on fatty liver in mice was realized by blocking miR-34a, targeting PPARα signaling pathways.