Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
J Dig Dis. 2010 Apr;11(2):94-100. doi: 10.1111/j.1751-2980.2010.00422.x.
To investigate the expression and significance of thioredoxin messenger ribonucleic acid (mRNA) in the development of non-alcoholic fatty liver disease (NAFLD) induced by a high fat diet.
A total of 48 male Wistar rats were divided into a normal control group and a model group, which were both divided into three subgroups (at weeks 9, 13 and 18, respectively). The levels of serum tumor necrosis factor-alpha (TNF-alpha), free fatty acid (FFA), total cholesterol (TC) and triglyeride (TG), changes in the serum and hepatic tissue superoxide dismutase (SOD), reduced glutathione hormone (GSH) and malondialdehyde (MDA) were measured. The expression of thioredoxin mRNA in rat livers were detected with reverse transcriptase polymerase chain reaction (RT-PCR). Meanwhile, the pathological changes of liver tissue were observed by hematoxylin-eosin stain.
Simple fatty liver was observed in model group at week 9. From weeks 13 to 18, liver histopathology showed steatohepatitis. Compared with corresponding normal groups, in the model groups the levels of TNF-alpha, FFA, TC, TG in serum, and MDA in serum and liver increased significantly, while the vitality of SOD and GSH content in serum and liver decreased remarkably. Meanwhile, in the model group, the expression of hepatic thioredoxin mRNA was significantly decreased at week 9 compared with the normal group (P < 0.01), then increased gradually, but were lower than the corresponding normal groups at all times (P < 0.01).
The expression of thioredoxin mRNA is significantly lower in the liver of rats with NAFLD and might reach the lowest point after developing simple fatty liver. Meanwhile the downregulation of thioredoxin mRNA may cause the inflammatory injury initially in NAFLD.
探讨硫氧还蛋白信使核糖核酸(mRNA)在高脂饮食诱导非酒精性脂肪性肝病(NAFLD)发生发展过程中的表达及意义。
雄性 Wistar 大鼠 48 只,随机分为正常对照组和模型组,每组又分为 3 个亚组(9、13、18 周末)。检测血清肿瘤坏死因子-α(TNF-α)、游离脂肪酸(FFA)、总胆固醇(TC)、三酰甘油(TG)水平,血清和肝组织中超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)、丙二醛(MDA)的变化,采用逆转录聚合酶链反应(RT-PCR)检测大鼠肝脏硫氧还蛋白 mRNA 的表达,苏木精-伊红(HE)染色观察肝组织病理学变化。
模型组大鼠在 9 周末出现单纯性脂肪肝,13 周末至 18 周末出现脂肪性肝炎,与相应正常组比较,模型组大鼠血清 TNF-α、FFA、TC、TG 及血清和肝组织 MDA 水平明显升高,血清和肝组织 SOD、GSH 活力明显降低;模型组大鼠肝组织硫氧还蛋白 mRNA 表达在 9 周末较正常组明显降低(P<0.01),随后逐渐升高,但各时间点均低于相应正常组(P<0.01)。
NAFLD 大鼠肝脏中硫氧还蛋白 mRNA 表达明显降低,可能在发生单纯性脂肪肝后降至最低,硫氧还蛋白 mRNA 下调可能导致 NAFLD 早期发生炎症损伤。