己酮可可碱治疗非酒精性脂肪性肝炎的实验研究

A Trial of Pentoxifylline in Rat Nonalcoholic Steatohepatitis

目的通过高脂饮食制备大鼠非酒精性脂肪肝模型,观察肝组织胶原的合成及相关细胞因子的变化。进一步观察及探讨己酮可可碱(pentoxifylline,PTX)对非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)所致肝纤维化的治疗作用及机制。方法30只SD大鼠随机分为模型组(n=10)、治疗组(n=10)和正常对照组(n=10)3组。模型组和治疗组大鼠以高脂饲料喂养,治疗组大鼠高脂饮食12周后每d同时予以己酮可可碱16mg/kg,及治疗4周。对照组大鼠以普通饲料饲养。实验16周处死3组大鼠。应用荧光定量PCR方法分别测定肝组织Ⅰ、Ⅲ型前胶原(procollagenⅠ、Ⅲ)、转化生长因子-β1(TGF-β1)及肿瘤坏死因子-α(TNF-α)的水平。结果大鼠肝组织中Ⅰ型前胶原mRNA的表达量模型组高于对照组,治疗组显著低于模型组,差异有统计学意义(P<0.05);大鼠肝组织中Ⅲ型前胶原mRNA的表达量,模型组高于对照组,差异有统计学意义(P<0.05),治疗组与模型组表达量差异无统计学意义;大鼠肝组织中TGF-β1 mRNA的表达量模型组高于对照组,治疗组显著低于模型组,差异有统计学意义(P<0.05);大鼠肝组织中TNF-α mRNA的表达量模型组高于对照组,治疗组显著低于模型组,差异有统计学意义(P<0.05)。结论TGF-β及TNF-α可能参与非酒精性脂肪肝肝纤维化的发生、发展过程。己酮可可碱可能通过抑制细胞因子TGF-β1和TNF-α降低脂肪性肝炎肝脏细胞外基质Ⅰ、Ⅲ型胶原的合成,对NASH引起的肝纤维化起到一定的治疗作用。

Objective To investigate the effects and mechanism of pentoxifylline on nonalcoholic steatohepatitis. Methods Thirty SD rats were divided into 3 groups randomly： model group （n = 10）, treatment group（n = 10）, and normal control group（n = 10）. The rats of model group and treatment group were given fat-rich feed, and those of normal control group were given normal feed. Furthermore, the rats of treatment group were given pentoxifylline after 12 weeks of fat-rich diet feeding. At 16 weeks, the rats of treatment group, normal control group and model group were sacrificed. Livers were reserved to measure the procollagen Ⅰ , procollagen Ⅲ, TGF-β1 and TNF-α mRNA expression by real-time PCR. Results The model group＇s procollagen I mRNA expression level was higher than that of the normal control group（P 〈0.05）, that of the treatment group was lower than that of the model group（P 〈0.05）. Model group＇s procollagen Ⅲ mRNA expression level was higher than that of the normal control group （ P 〈 0.05 ）, that of the treatment group was lower than that of the model group, but the differences were no statistically significant. The model group＇s TGF-β1 mRNA expression level was higher than that of normal control group（ P 〈 0.05 ）, that of treatment group was lower than that of model group（P 〈 0.05 ）. Model group＇s TNF-α mRNA expression level was higher than that of normal control group （ P 〈 0.05 ）, and that of treatment group was lower than that of model group （ P 〈 0.05 ）. Conclusion Pentoxifylline can decrease the collagen I and collagen Ⅲ mRNA expression of nonalcoholic steatohepatitis, inhibit TGF-β1 and TNF-α expression. Pentoxifylline may have certain anti-fibrotic effects.