吡格列酮治疗大鼠非酒精性脂肪性肝病的研究

Therapeutic effects of pioglitazone on rat with fatty liver induced by high fat diet

目的观察胰岛素抵抗与非酒精性脂肪性肝病的关系,探讨吡格列酮对高脂喂养诱导大鼠脂肪肝的治疗作用。方法32只雄性SD大鼠分为3组：对照组(11只)喂饲普通饮食16周,模型组(10只)喂饲高脂饮食16周,药物组(11只)为高脂饮食喂饲8周后改为高脂饮食同时加用吡格列酮4 mg·kg^(-1)·d^(-1)灌胃8周。16周末处死大鼠,称量肝湿重及体重,测定丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)和血糖水平。用放射免疫法测定空腹胰岛素和肿瘤坏死因子(TNF)-α,计算胰岛素抵抗指数(HOMA-IR),并观察肝脏病理变化。结果16周末,模型组肝脏出现明显肝细胞脂肪变性和肝小叶炎症,肝指数、ALT、AST、ALP、胰岛素水平及HOMA-IR均高于对照组(P＜0．05)；药物组和模型组相比,脂肪变性和肝小叶炎症明显减轻,肝指数、ALT、ALP、TNF-α和HOMA- IR均降低(P＜0．05),胰岛素水平有降低趋势。结论高脂喂养脂肪肝大鼠随病变进展可能存在胰岛素抵抗。吡格列酮治疗可以改善或延缓大鼠脂肪肝病变程度。

Objective To investigate the association between insulin resistance and nonalcoholic fatty liver disease （NAFLD）, and to evaluate the role of pioglitazone （PGZ） in treatment of rat with fatty liver induced by high fat feeding. Methods The SD rats were randomly divided into 3 groups. The rats in model group were fed with high fat diet for 16 weeks. The rats in PGZ treatment group were given high fat diet for 8 weeks, then gavaged with PGZ （44 mg·kg^-1·d^-1 ） and high fat diet for 8 weeks. The rats in control group were fed with normal food for 16 weeks. All rats were sacrificed in the end of 16 weeks to weigh liver and body masses. Serum activities of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphstase （ALP） and fasting blood glucose （FBG） were detected. Tumor necrosis factor alpha （TNF-α） and fasting plasma insulin （FINS） were measured by RIA. HOMA insulin resistance index （HOMA-IR） and the liver histology were assayed. Results At the end of 16 weeks, notable steatosis and lobular necroinflammatory change were found in model group, while the degree of steatosis and hepatic lobular inflammation were attenuated in PGZ treatment group （P〈0.05）. Liver index, serum level of ALT, AST, ALP, FINS and HOMA-IR were significantly increased （P〈0.05） in model group compared with control group. Whereas, compared with model group, serum level of AST and FINS showed an decreasing tendency, liver index, serum level of ALT, ALP, TNF-α and HOMA-IR were significantly decreased in PGZ treatment group. Conclusion The development of NAFLD can induce insulin resistance in rats. Pioglitazone is able to attenuate insulin resistance and sequela of NAFLD.