高血糖对非酒精性脂肪性肝炎大鼠肝星状细胞活化作用的研究

目的：观察高血糖在非酒精性脂肪性肝炎（NASH）、肝纤维化形成中的作用以及此过程中肝星状细胞的活化机制。方法将60只SD大鼠分成正常对照组、高血糖模型组、复合模型组、氨基胍组和格列美脲组5组，分别检测各组大鼠血糖值，HE染色观察肝组织的病理改变，Masson染色观察肝脏纤维组织变化，免疫组化检测α-平滑肌动蛋白（α- SMA）的表达评分、ELISA法检测基质金属蛋白酶组织抑制因子-1（TIMP-1）、转化生长因子-β1（TGF-β1）和晚期糖基化终产物（AGEs）含量的变化。结果氨基胍组、格列美脲组大鼠的血糖值较高血糖模型组和复合模型组均降低（均P＜0.05）；光镜下观察高血糖模型组和复合模型组出现肝细胞变性和纤维化改变。与复合模型组比较，格列美脲组肝细胞形态较正常，可见轻度水肿、脂肪变性及炎细胞浸润，纤维化明显降低，α- SMA表达明显降低，TIMP-1、TGF-β1、AGEs含量也显著降低，均有统计学差异（均P＜0.01）。与复合模型组比较，氨基胍组肝组织形态明显改善，脂肪变性、水样变性、纤维化程度有所减轻，TIMP-1、AGEs含量降低（均P＜0.01），α- SMA表达增高（P＜0.05），同时TGF-β1表达减低，但无统计学差异（P＞0.05）。结论高血糖促进了NASH、肝纤维化的形成，通过降低血糖和减少AGEs形成后，肝纤维化程度也有所减轻；机制之一是激活肝星状细胞。格列美脲较氨基胍改善NASH、肝纤维化更明显。

Effects of hyperglycemia on activation of hepatic stellate cells in rats with non-alcoholic steatohepatitis

Objective To investigate the effects of hyperglycemia on activation of hepatic stel ate cells in rats with non- al-coholic steatohepatitis （NASH） and its mechanisms. Methods Sixty SD rats were divided into five groups with 12 in each：the control group, the hyperglycemia group, composite model （both hyperglycemia and NASH） group, aminoguanidine treatment group and glimepiride treatment group. Blood glucose was measured and serum TIMP- 1, TGF- β1, AGEs levels were assayed by ELISA. The pathological changes of liver tissue were observed by HE staining, liver fibrous tissue was ovserved by Masson stainning andα- SMA expression was detected by immunohistochemistry. Results The blood glucose was lower in two inter-vention group than that in hyperglycemia group and model group. In glimepiride group the hepatic tissue displayed a normal form, mild edema, fatty degeneration and inflammatory cellinfiltration; hepatic fibrosis was markedly al eviated, expression ofα- SMA was decreased, and TIMP- 1, TGF- β1 and AGEs levels were declined. There was no significant difference between di-abetic model group and composite model group. In aminoguanidine group the pathology of hepatic tissue was not improved sig-nificantly, but the fatty degeneration, hydropic degeneration, and hepatic fibrosis were slighly al eviated, TIMP- 1 and AGEs de-clined in content, but the expression ofα- SMA increased. Conclusion Hyperglycemia may promote the formation of hepatic fi-brosis and non- alcoholic steatohepatitis;glimepiride can effectively inhibit stel ate cellactivation, resulting in al eviation of hepatic fibrosis.