大鼠非酒精性脂肪肝形成过程中肝细胞增殖的变化

目的探讨大鼠非酒精性脂肪肝形成过程中肝细胞增殖的变化.方法通过高脂饮食建立Wistar大鼠非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)模型,同时设立正常饮食组作为对照,在实验第4、8、12周时分批收集肝脏标本.应用流式细胞术检测细胞周期,测定S期细胞比例(SPF)和增殖指数(PI),用免疫组织化学法检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达.结果高脂4周组和高脂8周组与对照组各项指标均无差异.高脂12周时SPF和PI明显高于对照组(P＜0.01),PCNA阳性率也明显升高(P＜0.01).结论大鼠NAFLD形成过程中肝细胞增生,主要发生在非酒精性脂肪肝炎(nonalcoholic steatohepatitis,NASH)形成后,这可能是肝脏对NASH引起的炎症、坏死的代偿反应,但是否为肝癌发生的早期事件值得重视.

Hepatocyte proliferation in the progression of nonalcoholic fatty liver in rats

Objective To explore the changes of hepatocyte proliferation in rats during the progression of nonalcoholic fatty liver disease (NAFLD). Methods Rat models of NAFLD were established by giving a fat-rich diet. The rats fed with normal diet were taken as normal control at the same stage during the study. These rats were sacrificed at week 4, 8, and 12 respectively and collected the liver tissues. The cell cycle and the changes of the S-phase cell fraction (SPF), proliferation index (PI) was measured by flow cytometry. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. Results There was no significant difference between NAFLD group and the control group at week 4, 8. But as compared with the control group, SPF and PI of 12-week group were significantly increased and PCNA labeling index were also higher. Conclusion Hepatic hyperplasia occurred after the nonalcoholic steatohepatitis was established in the rat models of NAFLD. Hepatic hyperplasia probably was the reaction of inflammation and necrosis, but whether it was the early incident of hepatocarcinoma should be paid attention.