过氧化物酶体增殖物激活受体α在实验性大鼠脂肪肝中的表达

目的:研究过氧化物酶体增殖物激活受体α(PPARα)表达异常在脂肪肝发生中的作用。方法:采用小剂量CCl₄后肢皮下注射, 并高脂饮食复制大鼠脂肪肝动物模型, 检测肝脏甘油三酯(TG)、总胆固醇(TC)和游离脂肪酸(FFA)含量及血清谷丙转氨酶(ALT)、肿瘤坏死因子-α(TNF-α)和FFA含量, 并做病理切片, 测定肝脂变面积。提取肝脏总RNA, 运用半定量RT-PCR方法对肝脏PPARαmRNA的表达情况进行分析。结果:脂肪肝模型组大鼠肝脏TG、TC、FFA含量分别为(1.88±0.20)mmol·L^-1、(11.03±1.12)mmol·L^-1和(1260.38±151.27)μmol·L^-1, 正常对照组则为(0.53±0.10)mmol·L^-1、(1.25±0.25)mmol·L^-1和(334.30±27.09)μmol·L^-1(P＜0.01)。血清ALT、TNF-α和FFA含量亦明显高于对照组。肝脏PPARα的灰度比值:脂肪肝模型组0.41±0.28, 正常对照组1.41±0.29(P＜0.01)。结论:肝细胞中毒性脂肪肝时, 肝脏PPARα表达减少, 使肝中脂质的利用和脂肪酸的氧化均发生障碍, 导致肝脂蓄积。

Expression of peroxisome proliferator-activated receptor α in rat fatty liver

AIM:To investigate the role of expression of peroxisome proliferator-activated receptor α(PPAR α) in pathogenesis of rat fatty liver.METHODS:The rats were treated with a low dose of carbon terachloride (CCl₄) and fed a high fat diet to produce fatty liver. We determined the concentrations of triglyceride (TG), total cholesterol (TC), free fatty acid (FFA) in liver and the alanine aminotransferase (ALT) activity, tumor necrosis factor-α (TNF-α), FFA in serum and the degree of hepatocytic steatosis. Total RNA of liver was extracted, and the expression of PPAR α were analyzed by semi-quantitative RT-PCR method.RESULTS:In model group, the hepatocytic PPAR α mRNA expression decreased to 0.41±0.28, compared to 1.41±0.29 in the control group (P＜0.01). The contents of TG, TC, FFA in model rat liver were (1.88±0.20) mmol·L^-1, (11.03±1.12) mmol·L^-1 and (1 260.38±151.27) μmol·L^-1, respectively, compared to (0.53±0.10) mmol·L^-1, (1.25±0.25) mmol·L^-1 and (334.30±27.09) μmol·L^-1 in the control group (P＜0.01). The activity of ALT, concentrations of TNF-α and FFA in serum were also increased remarkably in model group.CONCLUSION:Oxidation of fatty acid and utilization of lipids in liver are affected by reducing the expression of PPAR α, which result lipid accumulation in liver.