PPARα及Acox1在酒精性脂肪肝中的表达

发布时间：2019-01-26 13:26

【摘要】：目的通过测定酒精性脂肪肝大鼠血清TNF-α、肝内甘油三酯、PPARαmRNA及Acox1mRNA含量、肝内PPARα蛋白含量,并通过PPARα激动剂苯扎贝特(Bezafibrate)的干预研究,探讨酒精性脂肪肝大鼠肝内甘油三酯沉积的分子生物学机制及酒精性脂肪肝的发病机制。方法将60只Wistar大鼠随机分为正常对照组(n=20)、酒精性脂肪肝组(n=20)及苯扎贝特组(n=20)。正常对照组予蒸馏水灌胃8周;酒精性脂肪肝组给予鱼油2.5mL/kg+乙醇灌胃8周;苯扎贝特组采用鱼油+乙醇灌胃,4周后加用苯扎贝特100mg/kg灌胃治疗4周。第8周取腹腔静脉血及肝组织,采用ELISA法测定血清TNF-α含量;比色法测定肝脏甘油三酯沉积;RT-PCR法测定肝内PPARαmRNA及Acox1mRNA含量;Western blot法测定肝内PPARα蛋白含量。结果与正常对照组相比,酒精性脂肪肝组大鼠血清内TNF-α含量升高[(3.01±0.31)ng/mL vs.(1.07±0.28)ng/mL,P0.01],肝内甘油三酯沉积增多[(0.72±0.09)mmol/L vs.(0.28±0.07)mmol/L,P0.01],肝内PPARαmRNA[(0.22±0.08)vs.(0.68±0.13),P0.01]及Acox1 mRNA[(0.43±0.12)vs.(1.14±0.21),P0.01]表达减少,PPARα蛋白含量减少[(0.19±0.07)vs.(0.48±0.11),P0.01]。经苯扎贝特治疗后,苯扎贝特组大鼠血清内TNF-α含量降低,肝内甘油三酯沉积减少,肝内PPARαmRNA及Acox1mRNA表达增多,PPARα蛋白含量增多。结论酒精性脂肪肝大鼠肝内PPARα及Acox1表达减少,从而影响脂肪酸的代谢,导致肝内甘油三酯沉积增多,血清内TNF-α含量升高,引起酒精性脂肪肝。苯扎贝特可通过激活PPARα,使肝内PPARα及Acox1表达增加,促进脂肪酸的代谢,减少肝内甘油三酯沉积,降低血清内TNF-α含量,起到预防和治疗酒精性脂肪肝的作用。
[Abstract]:Objective to determine the contents of serum TNF- 伪, triglyceride, PPAR 伪 mRNA and Acox1mRNA, and the content of PPAR 伪 protein in liver of rats with alcoholic fatty liver. To investigate the molecular biological mechanism of triglyceride deposition in the liver of rats with alcoholic fatty liver and the pathogenesis of alcoholic fatty liver. Methods 60 Wistar rats were randomly divided into three groups: normal control group (n = 20), alcoholic fatty liver group (n = 20) and benzafibrate group (n = 20). The normal control group was fed with distilled water for 8 weeks, the alcoholic fatty liver group with fish oil 2.5mL/kg ethanol for 8 weeks, and the benzabette group with fish oil ethanol for 4 weeks. At the 8th week, serum TNF- 伪 was determined by ELISA method, triglyceride deposition by colorimetry, PPAR 伪 mRNA by RT-PCR and PPAR 伪 protein by Acox1mRNA; Western blot. Results compared with the control group, the serum TNF- 伪 level in the alcoholic fatty liver group increased [(3.01 卤0.31) ng/mL vs. (1.07 卤0.28) ng/mL,P0.01]. Intrahepatic triglyceride deposition increased [(0.72 卤0.09) mmol/L vs. (0.28 卤0.07) mmol/L,P0.01], intrahepatic PPAR 伪 mRNA [(0.22 卤0.08) vs. () 0.68 卤0.13]. P0.01 and Acox1 mRNA [(0.43 卤0.12) vs. (1.14 卤0.21), P0.01] decreased and PPAR 伪 protein content decreased [(0.19 卤0.07) vs. () 0.48 卤0.11, P0.01]. After treatment with benzabetine, the content of TNF- 伪 in serum, the deposition of triglyceride in liver, the expression of PPAR 伪 mRNA and Acox1mRNA in liver, and the protein content of PPAR 伪 in serum of rats in the group B were decreased. Conclusion the expression of PPAR 伪 and Acox1 in the liver of rats with alcoholic fatty liver decreased, which affected the metabolism of fatty acids, increased the accumulation of triglycerides in the liver and increased the content of TNF- 伪 in serum, which resulted in the alcoholic fatty liver. By activating PPAR 伪, the expression of PPAR 伪 and Acox1 in liver was increased, fatty acid metabolism was promoted, triglyceride deposition in liver was decreased and TNF- 伪 content in serum was decreased, which could prevent and treat alcoholic fatty liver.
【作者单位】：三峡大学消化疾病研究所宜昌市中心人民医院消化内科;
【基金】：湖北省宜昌市科技计划资助项目(No.A09301-07)
【分类号】：R575.5

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