非酒精性脂肪性肝炎大鼠血清肿瘤坏死因子α变化和肝组织过氧化物酶体增殖物激活受体γ的表达

Changes of tumor necrosis factor alpha and expression of peroxisomal proliferator-activated receptor γ in rats of nonalcoholic steatohepatitis

目的探讨TNFα和PPARγ在高脂饮食所致脂肪性肝炎形成中的作用。方法雄性SD大鼠30只随机分组为3组,每组10只,正常组普通饲料喂养;模型Ⅰ、Ⅱ组喂高脂饲料。12周末处死正常组和模型Ⅰ组大鼠,模型Ⅱ组大鼠继续喂养至16周末处死.测定血清肿瘤坏死因子α(TNFα)含量,肝匀浆丙二醛(MDA)含量,观察肝组织学改变,免疫组化法测PPARγ表达。结果模型组大鼠肝组织脂质过氧化产物MDA含量与正常组比明显升高(Ⅰ组6.45±1.07,Ⅱ组8.38±1.32μmol/g,vs正常组5.08±0.91μmol/g,P<0.01),血清TNFα水平明显增高(1.95±0.39,2.48±0.50μg/Lvs0.82±0.18μg/L,P<0.01),肝脏的脂肪变性程度和炎症活动度计分均显著增高(P<0.05),PPARγ阳性表达细胞明显减少(P<0.05),但与脂肪变性的严重程度无关,而与肝组织的炎症活动度呈负相关。结论TNFα为非酒精性脂肪肝发病过程中胰岛素抵抗的一个关键性介质,PPARγ表达减弱在NASH大鼠模型脂质过氧化、炎症介质释放、肝组织损伤等方面起着关键作用。

Objective To explore the action of tumor necrosis factor alpha （TNFα） and peroxisomal prolifemtor-actirated receptor T（PPARγ） in the establishment of steatohepatitis in rats fed by high-fat diets. Methods Thirty male Sprague Dawley rots were randomly assigned into 3 groups. The rots fed by normal food served as the controls. The rots in model group （Ⅰand Ⅱ） were fed with high-fat diets. The rots in control and model Ⅰ group were killed at 12 wk and the rest（group Ⅱ ） were killed at 16 wk. Blood sample were collected for the detection of serum tumor necrosis factor alpha （TNFα）, and liver tissues were obtained for the detection of malondialdehyde （MDA） contents. The histological changes were observed under light microscope and PPAR T was detected by immuneohistochemistry. Results In comparison with those of normal rots, the contents of MDA （in group Ⅱ ：8.38 ± 1.32 μmol/g） vs control group：5.08 ±0.91 μmol/g, P 〈 0.01）and TNFa（group Ⅱ ： 2.48 ± 0.50 μg/L vs control group：0.82 ± 0.18 μg/L, P 〈 0.01） were increased significantly. The severity degree of hepatic fatty degeneration aggravated and inflammation score were increased markedly（ P 〈 0.05）, The number of PPAR γ immunostaining positive expression cells were decreased significantly（ P 〈 0.05） and were independent to severity degree of liver steatosis, but having negative correlation to inflammation activity degree of liver tissue. Conclusion TNFα is a key factor of insulin resistance in the formation of NASH and weakening of PPARγ expression may play a key role in liver lipid pemxidation, inflammation medium releasing and liver tissue damnification.