摘要
目的观察非酒精性脂肪性肝病(NAFLD)模型大鼠肝脏抵抗素mRNA的动态表达,探讨抵抗素在大鼠NAFLD发病中的作用。方法雄性Wistar大鼠48只随机分为正常对照组(C组)和模型组(M组),C组给予普通饲料,M组给予高脂饮食喂养,分别于9,13,17周末处死各组大鼠。测定大鼠血清肿瘤坏死因子α(TNF-α)、游离脂肪酸(FFA)、甘油三酯(TG)、总胆固醇(TC),以及肝组织TG,测定空腹血糖(FBS)、空腹胰岛素(FINS),并计算胰岛素敏感指数(ISI)。应用半定量RT-PCR检测各组大鼠肝脏组织抵抗素mRNA的表达;HE染色观察肝脏组织病理变化并计算炎症活动度计分。结果第9,13,17周末M组大鼠抵抗素mRNA相对表达量显著高于C组(P<0.01),且随造模时间延长表达量显著增加(P<0.01)。M组大鼠血清FFA、TG、TC、TNF-α及肝组织TG较同期C组均显著升高(P<0.01),ISI显著降低(P<0.01)。相关分析显示,M组大鼠各时点肝脏抵抗素mRNA相对表达量与血清TNF-α水平均呈正相关(r=0.787,0.888,0.873,P<0.05,P<0.01,P<0.01);在第9,13周末与肝脏炎症活动度计分呈正相关(r=0.861,0.892,P<0.01);而与ISI在第9周末呈负相关(r=-0.843,P<0.01)。结论高脂饮食NAFLD模型大鼠肝脏抵抗素基因表达随造模时间的延长而增加,抵抗素可以通过胰岛素抵抗及对炎症因子的调控参与NAFLD的发生发展。
Objective To investigate the expression of mRNA of resistin in the livers of rats with developing non-alcoholic fatty liver disease （NAFLD） and explore the effects of resistin in pathogenesis of the model of rats with NAFLD. Methods Frorty-eight male Wistar rats were randomly divided into 2 groups： control group （C group） and model group （M group）. The rats in C group were fed with standard diet, rats in M group fed with high-fat diet. At the end of9th, 13th, 17th week, the animals were sacrificed. The levels of FBS, TG, FFA, TC, TNF-α, FINS in serum and TG in liver tissue were detected, meanwhile the insulin sensitivity index （ISI） was calculated I ISI = 1 n[ 1/（ FINS ~ FBS）~ I. The expression of resistin mRNA was detected with RT- PCR; degrees of steatosis and steatohepatitis were observed. Results The expression level of resistin mRNA in livers of rats in M group was significantly higher than C group after 9 weeks and increased significantly with the time （P 〈0. 01 ）. The levels of FFA, TG, TC and TNF-α were significantly higher in M group than those in the C group （P 〈0.01 ）, but the levels of ISI was significantly lower （ P 〈0. 01 ）. A positive correlation was found between the expression level of resistin mRNA and the level of TNF-α in serum at the end of 9th, 13th and 17th week （ r =0. 787,0. 888,0. 873 ,P 〈0.05 ,P 〈0.01 ,P 〈0.01 ）, the degrees of steatohepatitis at the end of 9th and 13th week （r =0. 861,0. 892, P 〈0. 01 ） ; resistin levels were negatively correlated with ISI at the end of 9th week （R = - 0. 834, P 〈 0. 01 ）. Conclusion The expression of resistin mRNA was up-regulated in liver of NAFLD model rats. Resistin may participate in the development of NAFLD through impairment of insulin action and as a regulatory cytokine of pro-inflammatory cytokines.
出处
《国际内科学杂志》
CAS
2007年第11期628-631,640,共5页
International Journal of Internal Medicine
