摘要
目的基于Notch1信号通路探讨白藜芦醇对非酒精性脂肪性肝病(NAFLD)的影响。方法选取10只C57BL/6J雄性小鼠作为正常组,给予普通饲料喂养;另取30只C57BL/6J雄性小鼠给予高脂饲料喂养12周建立NAFLD模型,将建模成功的小鼠随机分为3组各10只。白藜芦醇低剂量组、白藜芦醇高剂量组分别给予50 mg/(kg·d)和100 mg/(kg·d)白藜芦醇灌胃,高脂组和正常组给予生理盐水灌胃,均1次/d,连续灌胃6周。灌胃结束后,测定各组小鼠血清三酰甘油(TC)、总胆固醇(TG)水平;HE染色观察肝脏组织病理改变;油红染色观察肝脏脂肪沉积情况;RT-qPCR法检测各组小鼠肝脏组织中固醇调节元件结合蛋白-1c(SREBP-1c)和过氧化物酶增殖物激活受体α(PPAR-α)mRNA表达情况;蛋白质印迹法检测各组小鼠肝脏组织中Notch1表达情况。结果高脂组小鼠血清TG、TC水平均明显高于正常组(P均<0.05);白藜芦醇低、高剂量组小鼠血清TG、TC水平均明显低于高脂组(P均<0.05),白藜芦醇高剂量组均明显低于白藜芦醇低剂量组(P均<0.05)。HE染色显示,高脂组小鼠肝细胞结构紊乱,有坏死现象,肝细胞脂滴空泡较多;白藜芦醇低、高剂量组小鼠肝坏死细胞和脂肪空泡较少;油红染色显示,高脂组小鼠肝脏橘红色脂滴沉积较多,白藜芦醇低、高剂量组小鼠橘红色沉积较少。与正常组比较,高脂组小鼠肝脏组织中SREBP-1c mRNA和Notch1蛋白相对表达量均明显增高(P均<0.05),PPAR-αmRNA相对表达量明显降低(P<0.05);与高脂组比较,白藜芦醇低、高剂量组小鼠肝脏组织中SREBP-1c mRNA和Notch1蛋白相对表达量均明显降低(P均<0.05),PPAR-αmRNA相对表达量均明显增高(P均<0.05),且白藜芦醇高剂量组各指标改善较白藜芦醇低剂量组明显(P均<0.05)。结论白藜芦醇能够改善NAFLD病理改变,其机制可能与抑制Notch1信号通路进而减少肝脏脂肪合成有关。
Objective It is to investigate the effect of resveratrol on non-alcoholic fatty liver disease(NAFLD)based on Notch1 signaling pathway.Methods Ten C57BL/6J male mice were selected as the normal group and fed with normal diet;another 30 C57BL/6J male mice were fed with high-fat diet for 12 weeks to establish NAFLD models,and the successfully modeled mice were randomly divided into 3 groups with 10 mice in each group.The low-dose resveratrol group and the high-dose resveratrol group were respectively given resveratrol 50 mg/(kg·d)and 100 mg/(kg·d)by gavage,and the high-fat group and normal group were given normal saline by gavage,all one time/d,continuous gavage for 6 weeks.After gavage,the levels of serum triacylglycerol(TC)and total cholesterol(TG)of the mice in each group were measured;the pathological changes of liver tissue were observed by HE staining;liver fat deposition was observed by oil red staining;the mRNA expression of sterol regulatory element-binding protein-1c(SREBP-1c)and peroxidase proliferator-activated receptor alpha(PPAR-α)in liver tissue of the mice in each group was detected by RT-qPCR;the expression of Notch1 in liver tissue of the mice in each group was detected by Western blotting method.Results The levels of serum TG and TC of the mice in the high-fat group were significantly higher than those in the normal group(all P<0.05),and the levels of serum TG and TC of the mice in the low-dose and high-dose resveratrol groups were significantly lower than those in the high-fat group(all P<0.05).HE staining showed that the structure of liver cells in the high-fat group was disordered,with necrosis and more lipid droplet vacuoles in the liver;there were fewer necrotic cells and fat vacuoles in the liver of the mice in the low-dose and high-dose resveratrol groups;oil red staining showed that there were more orange-red lipid droplets in the liver of the mice in the high-fat group,and less orange-red deposition in the low-dose and high-dose resveratrol groups.Compared with the normal group,the relative expressions of SREBP-1c mRNA and Notch1 protein in the liver tissue of the mice in the high-fat group were significantly increased(P<0.05),and the relative expression of PPAR-αmRNA was significantly decreased(P<0.05).Compared with the high-fat group,the relative expressions of SREBP-1c mRNA and Notch1 protein in the liver tissue of the mice in the low-and high-dose resveratrol groups were significantly decreased(all P<0.05),and the relative expression of PPAR-αmRNA was significantly increased(P<0.05).Conclusion Resveratrol can improve the pathological changes of NAFLD,and its mechanism may be related to inhibiting Notch1 signaling pathway thus to reducing hepatic fat synthesis.
作者
刘志红
刘静
孟令振
鲁明
王瑞英
LIU Zhihong;LIU Jing;MENG Lingzhen;LU Ming;WANG Ruiying(The Sencond Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei,China;The Fourth Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei,China)
出处
《现代中西医结合杂志》
CAS
2022年第17期2360-2364,2425,共6页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
河北省医学科学研究课题计划项目(20210115)。
