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目的 观察不同病因所致的脂肪性肝病大鼠肝组织核因子-κB(NF-κB)的活性变化,过氧化物酶体增殖物激活受体γ(PPAR γ)的表达,及其相互关系在脂肪性肝病炎症反应中的作用。方法40只Wistar 大鼠随机分为正常对照组、酒精组、高脂组和酒精加高脂4组,每组10只大鼠,16周断头处死,用HE、苏丹Ⅳ、Masson三色染色观察肝组织光镜下的病理改变和超微结构的变化。用电泳迁移率分析、逆转录聚合酶链反应观察各组大鼠肝组织NF-κB的活性变化与PPAR γ mRNA的表达、各生物化学指标间的相互关系。 结果 模型组大鼠肝组织均表现有不同程度的脂肪变性、炎症、坏死和纤维化,以酒精加高脂组病理损害最重。酒精组和酒精加高脂组的NF-κB活性(142±16.32,238±19.14)明显高于正常对照组(73±9.24,F值分别为6.36、17.93,P值均<0.01)和单纯高脂组(84±10.38,F值分别为5.96、16.20,P值均<0.01),酒精加高脂组的NF-κB活性显著高于酒精组(F=6.23,P<0.01),而高脂组和正常对照组比较差异无统计学意义。酒精组、高脂组和酒精加高脂组大鼠肝组织PPAR γmRNA的表达(0.2530±0.069,0.3647±0.082,0.1226±0.054)均较正常对照组(0.8097±0.094)有不同程度的减弱(F值分别为15.43、7.24、21.45,P值均<0.01)。相关分析显示:酒精组和酒精加高
Objective To observe the changes of hepatic NF-κB activity and peroxisome proliferator-activated receptorγ (PPARγ) expression in fatty liver caused by different etiologies, The role of fatty liver disease in inflammatory response. Methods Forty Wistar rats were randomly divided into four groups: normal control group, alcohol group, high fat group and alcohol plus high fat group. 10 rats in each group were sacrificed at 16 weeks after decapitation. HE, Sudan Ⅳ and Masson trichrome The pathological changes and ultrastructural changes of liver tissue under light microscope were observed. The electrophoretic mobility shift assay and reverse transcriptase polymerase chain reaction (RT-PCR) were used to observe the changes of NF-κB activity and the expression of PPARγ mRNA and the correlation between the biochemical indexes in liver tissue. Results The liver tissue of rats in model group showed varying degree of steatosis, inflammation, necrosis and fibrosis, and the pathological damage was the heaviest in alcohol-plus-fat group. The activity of NF-κB in alcohol group and alcohol plus hyperlipidemia group (142 ± 16.32,238 ± 19.14) was significantly higher than that in normal control group (73 ± 9.24, F value 6.36,17.93, P <0.01) Compared with the alcohol group (F = 6.23, P <0.01), the activity of NF-κB in the hyperglycemia group was significantly higher than that in the lipid group (84 ± 10.38, F = 5.96,16.20, P <0.01) There was no significant difference between the normal group and the control group. The expression of PPARγmRNA in liver tissue of alcohol group, high-fat group and alcohol-plus-fat group were significantly lower than that of normal control group (0.2530 ± 0.069,0.3647 ± 0.082, 0.1226 ± 0.054) Values were 15.43,7.24,21.45, P values were <0.01). Correlation analysis showed that alcohol group and alcohol increased