·糖尿病基础研究·

　　矫杰 李雅君 李晓沛 张彦 蔡瑾

　　基金项目：北京市自然科学基金资助项目(7062021)

　　作者单位：100029北京，首都医科大学附属北京安贞医院普内科

　　【摘要】 目的 观察罗格列酮预防非酒精性脂肪性肝炎(NASH)大鼠肝纤维化的作用。 方法 建立SD大鼠NASH伴肝纤维化的模型(HF24W)，同时高脂喂养大鼠12周后予罗格列酮(1?5mg·kg-1·d-1)干预12周(HF24W+RGZ12W组)。观察肝组织病理学改变，测定血清丙二醛(MDA)、肿瘤坏死因-α(TNF-α)、游离脂肪酸(FFA)、Ins、FPG，并计算胰岛素抵抗指数(HOMA-IR)。 结果 HF24W+RGZ12W组肝组织炎症、纤维化评分明显低于HF24W组(P<0?05)，脂肪变性与HF24W 组无统计学差异;HF24W+RGZ12W 组血清 MDA、TNF-α、FFA、Ins、HOMA-IR均明显低于HF24W 组(P<0?05)。 结论 罗格列酮可以减缓 NASH 大鼠肝纤维化的发生发展。

　　【关键词】罗格列酮;非酒精性脂肪性肝炎;肝纤维化;大鼠

　　doi:10.3969/j.issn.1006-6187.2011.01.015

　　The efficacy of rosiglitazone in prevention of hepatic fibrosis in rats with nonalcoholic steatohepatitis

　　JIAO Jie， LI Ya-jun， LI Xiao-pei， et al. Department of Medicine， Beijing Anzhen Hospital Affiliated to Capital Medical University， Beijing 100029， China

　　【Abstract】 Objective To investigate the therapeutic efficacy of rosiglitazone in prevention of hepatic fibrosis in rats with nonalcoholic steatohepatitis(NASH). Methods The high fat diet-induced NASH rats model with fibrosis were established(Group HF24W). The NASH rats fed for 12 weeks on higt-fat diet were further treated with rosiglitazone(1?5mg·kg-1·d-1) for 12 weeks(Group HF24W+RGZ12W). Histological changes in liver tissue in all groups were observed by HE staining and Masson staining. The levels of malondialdehyde(MDA)，tumor necrosis factor-α(TNF-α)， free fatty acid(FFA)，insulin(Ins) and fasting plasma glucose(FPG) in sera were measured respectively. Insulin resistance index(HOMA-IR) were calculated. Results The semi-quantification of inflammation and fibrosis were significantly lower in group HF24W+RGZ12W than in group HF24W (5?29±2?56 vs 12?75±3?59;5?50±1?38 vs 11?80±1?10，P<0?05). There was no difference in fat accumulation in hepatic tissue between group HF24W+RGZ12W and group HF24W(P>0?05).The levels of MDA， TNF-α， FFA， INS，HOMA-IR were significantly lower in group HF24W+RGZ12W than in group HF24W(34?08±11?35 vs 12?37±6?16;13?46±1?70 vs 10?44±1?72， 0?54±0?09 vs 0?19±0?08;41?57±10?30 vs 24?50±3?71;12?93±3?65 vs 7?16±0?93，P<0?05). Conclusions Rosiglitazone could retard the occurrence and progression of hepatic fibrosis in rats with NASH.

　　【Key words】Rosiglitazone; Nonalcoholic steatohepatitis; Hepatic fibrosis; Rats