消木丹颗粒对非酒精性脂肪性肝病大鼠TNF-α/NF-κB信号通路的影响

Effects of Xiaomudan Granule on the TNF-α/NF-κB signaling pathway in rats with non-alcoholic fatty liver disease

目的:研究消木丹颗粒对非酒精性脂肪性肝病(NAFLD)大鼠肿瘤坏死因子-α(TNF-α)/核因子κB(NF-κB)信号通路的影响。方法:70只SD大鼠按体质量随机分为空白组(10只)与实验组(60只),空白组以普通饲料喂养,实验组以高脂饲料喂养。实验第13周将造模成功的实验组大鼠按照体质量随机分为模型组,消木丹高、中、低剂量组和多烯磷脂酰胆碱组,同时给予相应药物灌胃。治疗4周后取材,检测各组肝指数、血脂及肝功能水平,观察肝脏组织病理改变。ELISA法检测血清TNF-α水平;免疫组化法和Western Blot法检测肝组织NF-κB蛋白表达情况;实时荧光定量PCR法检测NF-κB mRNA表达情况。结果:与空白组比较,模型组大鼠肝脏指数,血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、TNF-α水平,肝组织NF-κB表达量均显著上调(P<0.01),血清高密度脂蛋白胆固醇(HDL-C)下调(P<0.01);与模型组比较,消木丹中、高剂量组及多烯磷脂酰胆碱组大鼠肝脏指数,血清ALT、AST、TG、TC、LDL-C、TNF-α水平,肝组织NF-κB表达量均显著下调(P<0.05,P<0.01),血清HDL-C上调(P<0.01)。光镜下空白组大鼠肝细胞形态正常,模型组大鼠肝细胞出现脂肪变性,消木丹高、中剂量组及多烯磷脂酰胆碱组肝组织病理改变明显好转。结论:消木丹颗粒能够通过抑制TNF-α/NF-κB信号通路的表达而促进肝细胞修复从而保护NAFLD大鼠肝脏功能。

Objective:To research the effect of Xiaomudan Granule on the TNF-α/NF-κB signaling pathway in rats with non-alcoholic fatty liver disease(NAFLD).Methods:A total of 70 SD rats were divided into blank group 10 and experimental group 60 according to weight,blank group was fed with ordinary feed,and experimental group was fed with high fat feed.In the 13 th week of the experiment,the experimental group was divided into the model group,high,medium and low dose Xiaomudan treatment group and Polyene phosphatidyl choline treatment group according to body weight.At the same time,each group was given corresponding drugs by intragastric administration.Liver index,serum lipids and liver function were detected and the pathological changes of liver tissue were observed after 4 weeks of treatment.The expression of TNF-αlevel in serum was detected by ELISA,the expression of NF-κB protein in liver tissue was detected by immunohistochemistry and Western Blot,and the expression of NF-κB mRNA level in liver tissue was detected by PCR technology.Results:Compared with blank group,the liver index,the levels of ALT,AST,TG,TC,LDL-C,TNF-αin serum,NF-κB content in liver tissue in the model group were significantly increased(P<0.01)and HDL-C in serum were significantly decreased(P<0.01).Compared with the model group,the difference of the ALT,AST,TG,TC,LDL-C,TNF-αin serum,NF-κB content in liver tissue were significantly decreased in rat treated with Xiaomudan high,middle dose and Polyene phosphatidyl choline group(P<0.05,P<0.01),while HDL-C in serum were significantly increased(P<0.01).HE staining showed the hepatocyte morphology was normal in the blank group,fatty degeneration in model group,and the pathological changes of liver tissue were improved obviously in the high and medium dose Xiaomudan treatment group and Polyene phosphatidyl choline treatment group.Conclusion:Xiaomudan Granule can protect the liver function of NAFLD rats by inhibiting the expression of TNF-α/NF-κB signaling pathway and promoting the repair of hepatocytes.