己酮可可碱抑制非酒精性脂肪性肝炎TNF-α的实验研究

Therapeutic Effects of Pentoxifylline on Rat Nonalcoholic Steatohepatitis Is Mediated by Lowering Tumor Necrosis Factor alpha

目的探讨己酮可可碱pentoxifylline PTX对大鼠非酒精性脂肪性肝炎TNF-α表达的影响。方法雄性SD大鼠40只,随机分成正常对照组、模型组、治疗组3组,实验需16周。正常对照组(10只)饲以普通饲料,模型组(20只)及治疗组(10只)饲以高脂饲料。12周时从模型组中随机抽取10只处死,病理证实为脂肪性肝炎;余下的模型组及治疗组大鼠继续高脂饲料饲养,同时治疗组大鼠予以PTX16mg/kg.d灌胃4周。至16周时处死所有剩余大鼠,分别检测各组动物的体重、肝指数、血生化指标;进行HE染色观察肝脏病理学改变;并应用免疫组织化学方法分析和观察TNF-α表达。结果与模型组比较PTX治疗组大鼠体重、肝指数[(608.50±52.92)g对(668.00±62.86)g,(4.11±0.47)对(4.85±0.61),P<0.05和P<0.01]显著降低;肝脏生化得到改善[AST(120.20±34.59)U/L对(221.80±100.36)U/L,P<0.01];空腹血糖降低[(9.04±0.997)mmol/L对(10.58±1.871)mmol/L,P<0.05],且肝组织炎症活动度计分明显下降[(5.70±0.94)对(6.72±0.84),P<0.01]。组织化学显示TNF-α在肝脏中的表达显著降低[(0.172±0.042)对(0.43±0.038),P<0.01]。结论己酮可可碱可改善高脂饮食诱发的脂肪性肝炎大鼠肝脏酶学,减轻肝组织炎症损伤,具有治疗作用;其治疗机制之一可能是抑制TNF-α在肝脏中的表达。

Objective To study the therapeutic effects of pentoxifylline （PTX） on rat nonalcoholic steatohepatitis. Methods Forty male SD rats weighting 130 ~ 150 g were randomly divided into three groups： control group （ n = 10）, model group （ n = 20） and treatment group （ n = 10）. The control group were given normal diet, the model group and treatment group were given fat-rich diet. Ten rats of model group were sacrificed after 12 weeks of experiment. Then, the treatment group were given PTX （16 mg/kg·d） at 12 week of fat-rich diet feeding. At the end of 16 weeks, all rats were sacrificed and the serum samples and liver were investigated with the biochemistry, histopathology and immunohistochemistry for TNF-α. Results 1. At the end of experiment, compared with the model group, the body weight （608.50 ± 52.92 g vs 668.00 ± 62.86 g, P 〈 0.05）, liver index （4.11 ± O. 47 vs 4.85 ± 0. 61, P 〈 0.01 ）, the serum concentration of AST（ 120.20 ± 34.59 U/L vs 221.80 ± 100.36 U/L, P 〈 0.01 ）and FBG （9.04 ± 0.997 mmol/L vs 10,58 ± 1. 871 mmol/L, P 〈 0.05 ）in the treatment group were significantly lower,. 2. The hepatic inflammation scores decreased markedly in the treatment group （5.70 ± 0,94 vs 6.72 ± 0.84, P 〈 0.01 ）. 4. Compared with model group, the expression of TNF -α in treatment group was significantly decreased （0. 172 ± 0. 042 vs 0.43 ± 0.038, P 〈 0.01 ）. Conclusion The therapeutic effects of pentoxifylline on rat nonalcoholic steatohepatitis is possibly mediated by lowering TNF-α.