非酒精性脂肪肝病大鼠肝脏SOCS-3的表达与吡格列酮干预研究

Expression of SOCS-3 in the Liver of Rats with Nonalcoholic Fatty Liver Disease and Therapeutic Effects of Pioglitazone

目的:探讨SOCS-3在非酒精性脂肪肝病(NAFLD)发病中的作用以及吡格列酮的干预作用。方法:29只雄性SD大鼠随机分为正常对照组(8只),高脂饮食组(21只)。饲养8周后,从高质饮食组随机抽取5只大鼠证实造模成功后,将该组余下的16只大鼠继续以高脂饲料喂养,并随机分为NAFLD对照组(8只);吡格列酮干预组(8只),予以吡格列酮3mg·kg-·1d-1灌胃。16周末,处死所有大鼠,检测血糖、血胰岛素、血脂、肝脏SOCS-3 mRNA和SREBP-1c mRNA表达及肝脏病理学。结果:与正常对照组相比,NAFLD组血糖、血胰岛素、血脂、肝脏脂肪变水平及肝组织SOCS-3 mRNA、SREBP1c mRNA表达显著上调。吡格列酮干预组SOCS-3 mRNA、SREBP-1c mRNA表达较NAFLD组下调,且血糖、血胰岛素、血脂、肝脏脂肪变水平下降。SOCS-3 mRNA表达水平与胰岛素抵抗指数、SREBP-1c mRNA表达水平、肝脂肪变成显著正相关。结论:SOCS-3可能通过胰岛素抵抗及上调肝组织SREBP-1c mRNA表达参与NAFLD发病,吡格列酮能抑制肝脏SOCS-3的表达,对NAFLD有一定治疗作用。

To investigate the role of suppressors of cytokine signaling protein（SOCS-3） in the pathogenesis of patients with nonalcoholic fatty liver as well as the effects of pioglitazone. Methods： Twenty-nine male SD rats were randomized into normal control group （n=8, fed with normal food）, high fat diet group （n=21, fed with fat-rich food）. Killed 5 rats of high fat diet group after 8 weeks, and confirmed that the model of NAFLD was successfully established. Then the remaining 16 rats were divided into 2 subgroups： NAFLD control group （n=8, fed with continuously with fat-rich food）, pioglitazone intervention group （n=8, fed with continuously with fat-rich food and pioglitazone 3 mg.kg^-1·d^-1 by gastric perfusion）. By the end of 16^th week, all rats were killed to isolate the serum to test the levels of FBG, FINS, TG and TC. The SOCS-3 mRNA and SREBP-le mRNA expression of rat liver were analyzed by RT-PCR. Results： Compared with control group, the serum levels of FBG, FINS, TC, TG and the liver SOCS-3 and SREBP-lc expression levels, liver fatty degeneration grades of NAFLD group were all up-regulated （P〈0.05）. The serum levels of FBG, FINS, TC, TG ofpioglitazone intervention group were significantly lower than NAFLD control group （P〈0.05）; the liver SOCS-3 and SREBP-lc expression levels of pioglitazone intervention group were also lower than NAFLD control group（P〈0.05）. Meanwhile, the fatty degeneration grades of liver of pioglitazone intervention group was lower than NAFLD control group （P〈0.05）. The liver SOCS-3 mRNA expression levels positively correlated with HOMA-IR, the liver SREBP-lc mRNA expression levels and the fatty degeneration grades（P〈0.05）. Conclusion： SOCS-3 might be involved in nonalcoholic fatty liver through insulin resistance and up-regulating SREBP-1 c mRNA expression, and pioglitazone therapy could decrease the SOCS-3mRNA expression and effectively treat nonalcoholic fatty liver.