罗格列酮预防非酒精性脂肪性肝炎大鼠肝纤维化的研究

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、HOMAIR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。

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

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 facto-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.