微生态制剂美常安对高脂饮食所致的脂肪肝炎TNFα和PPARγ的影响

Effects of Microbial Drug on Tumor Necrosis Factor-alpha and Peroxisomal Proliferator-activated Receptor-γ in Rat Livers with Steatohepatitis Induced by High-fat Diets

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,微生态制剂防治非酒精性脂肪性肝炎的作用机制。方法雄性SD大鼠40只随机分为4组,每组10只。正常组普通饲料喂养;模型组喂高脂饲料,微生态制剂治疗组分别在喂饲高脂饲料12周后予美常安灌胃;饮食治疗组在喂饲高脂饲料12周后改为普通饲料喂养,16周末处死各组大鼠,测定血清转氨酶(ALT、AST)和肿瘤坏死因子α(TNFα)水平,肝匀浆丙二醛(MDA)含量,超氧化物歧化酶(SOD)活性,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MDA含量与正常组比较,(8.38±1.32μmol/g vs 5.08±0.91μmol/g,P<0.01)明显增高,血清TNFα水平(2.48±0.50μg/L vs 0.82±0.18μg/L,P<0.01)明显增高,而SOD活性(148±26 kNU/gt vs 198±25 kNU/gt,P<0.01)明显降低,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效关系。微生态制剂治疗组各项指标较模型组有明显改善(P<0.05或P<0.01),而饮食治疗组大鼠肝脏病理学仍呈轻-中度脂肪变性,炎症活动度计分较正常组显著增高(P<0.05),余各项指标与模型组比较无显著差异。结论微生态制剂美常安可能通过减少TNFα的产生,增加PPARγ表达等方面来改善胰岛素抵抗,抗脂质过氧化和抑制炎症反应。

Objective To explore the role of tumor necrosis factor-alpha （TNF-α and peroxisomal proliferator-activated receptor-γ （PPAR-γ） in the establishment of steatohepatitis and the therapeutic mechanisms of microbial pharmaceutics （MP） in its treatment in rats fed by high-fat diets. Methods Forty male Sprague Dawley rats were randomly assigned into four groups （ n = 10 in each group）. Group A Was fed with normal diets. The other three groups （ Group B, C and D） were fed with high-fat diets for 12 weeks. Group C was treated with microbial pharmaceuticals （ named as＂ lived combined B, subtilis and E. faecium enteric-coated capsules＂ with a trade name ＂ Meiehangan＂ ） and Group D turned to normal diets 12 weeks after. All the rats were executed at the end of 16 weeks. Blood samples were collected for detection of serum aspartate transaminase （ AST）, alanine aminotransferase （ALT） and TNF-α, and liver tissues were obtained for detection of malondialdehyde （MDA） content, superoxide dismutase （SOD） activity and total antioxidative capacity （T-AOC）. Histological changes were observed under light microscope and PPAR-γ was detected by immuneohistochemistry. Results In comparison with that of Group A, the contents of MDA and TNF-α of Group B were significandy increased （ 8.38 ± 1.32 vs 5.08 ± 0.91 μmol/g, P 〈 0.01 ; 2.48 ± 0.50 vs 0.82 ± 0. 18 μ/L, P 〈 0. 01 ） but the content of anti-oxide SOD was decreased Significantly （ 148 ± 26 vs 198 ± 25 kNU/gt, P 〈 0. 01 ） and the severity of hepatic fatty degeneration was aggravated and the inflammation score was increased markedly （ P 〈 0. 01 ）. The number of PPAR-γ positive expression cells was decreased significandy, which was independent of severity of liver steatosis and was negatively correlated to inflammation activity in liver tissue. In comparison with that of Group B, the markers such as MDA, SOD, TNF-αand PPAR-γ were all significantly improved in Group C, as well as the severity of fatty degeneration （ P 〈 0.05 or P 〈 0.01 ）. Slight or moderate fatty degeneration was observed and inflammation score was increased significantly in Group D when compared with that of Group A （P 〈 0. 05 ）. Also in Group D, the other relative markers were not notably different from that of Group B. Conclusion Microbial pharmaceutical ＂Meichanganhas＂ the action of ameliorating insulin resistance, anti-lipid peroxidation and anti-inflammation. The mechanisms may be related to decreasing the contents of TNF-α and enhancing PPAR-γ expression.