Cong L I, Xiao-Hui Liu, Hai-Rong Xiong, Xiao-Xiao L I, Yue Luo, Chao-Qi Liu
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University Yichang 443002, China.
Medical College of China Three Gorges University Yichang 443002, China.
Zhongguo Zhong Yao Za Zhi. 2020 Oct;45(19):4725-4731. doi: 10.19540/j.cnki.cjcmm.20200427.401.
To study the effect of Panax japonicas saponin Ⅳa(SPJ-Ⅳa) on nonalcoholic steatohepatitis(NASH) through miR-17-5 p/MFN2 signaling pathway. The nonalcoholic steatohepatitis model was induced by a high-fat diet combined with CCl_4 in Balb/c male mice. The mouse serum and liver were collected, the body weight and liver weight were measured, the liver index was calculated, and the serum biochemical indicators alanine amino transferase(ALT), triglyceride(TG), and glucose(Glu) were measured. The morphological changes in the liver were detected by HE and Masson staining, Real-time PCR was used to detect lipid metabolism-related genes, inflammation-related genes interleukin-6(IL-6) and interleukin-1β(IL-1β), miR-17-5 p and MFN2 expressions, and Western blot was used to detect MFN2 protein expression level. Compared with the normal control group, the liver index in the HFD+CCl_4 group was significantly increased, and the contents of ALT, TG, and Glu were significantly increased; the morphology showed obvious steatosis and collagen fiber deposition; mRNA expression levels of lipid metabolism-related genes, inflammation-related genes and miR-17-5 p increased significantly, the mRNA expression level of MFN2 decreased significantly, and the protein level of MFN2 decreased. After intervention with SPJ-Ⅳa, the levels of ALT, TG and Glu decreased, morphological steatosis decreased, collagen fiber deposition decreased, and mRNA expression levels of lipid metabolism-related genes, inflammation-related genes and miR-17-5 p decreased. The mRNA expression level of MFN2 increased, and the protein level of MFN2 also increased. The results of this study indicated that miR-17-5 p/MFN2 signaling pathway may be involved in the occurrence and development of NASH, and SPJ-Ⅳa had a protective effect on NASH, its mechanism may be related to the regulation of miR-17-5 p/MFN2 signaling pathway.
通过miR-17-5p/MFN2信号通路研究竹节人参皂苷Ⅳa(SPJ-Ⅳa)对非酒精性脂肪性肝炎(NASH)的影响。采用高脂饮食联合四氯化碳诱导Balb/c雄性小鼠建立非酒精性脂肪性肝炎模型。收集小鼠血清和肝脏,测量体重和肝脏重量,计算肝脏指数,并检测血清生化指标谷丙转氨酶(ALT)、甘油三酯(TG)和葡萄糖(Glu)。通过HE和Masson染色检测肝脏的形态学变化,采用实时荧光定量PCR检测脂质代谢相关基因、炎症相关基因白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)、miR-17-5p和MFN2的表达,采用蛋白质印迹法检测MFN2蛋白表达水平。与正常对照组相比,高脂饮食+四氯化碳组肝脏指数显著升高,ALT、TG和Glu含量显著升高;形态学表现为明显的脂肪变性和胶原纤维沉积;脂质代谢相关基因、炎症相关基因和miR-17-5p的mRNA表达水平显著升高,MFN2的mRNA表达水平显著降低,MFN2蛋白水平降低。SPJ-Ⅳa干预后,ALT、TG和Glu水平降低,形态学脂肪变性减轻,胶原纤维沉积减少,脂质代谢相关基因、炎症相关基因和miR-17-5p的mRNA表达水平降低。MFN2的mRNA表达水平升高,MFN2蛋白水平也升高。本研究结果表明,miR-17-5p/MFN2信号通路可能参与NASH的发生发展,SPJ-Ⅳa对NASH具有保护作用,其机制可能与调控miR-17-5p/MFN2信号通路有关。