高血糖对大鼠肝星状细胞活化及转化生长因子-β1和结缔组织生长因子表达的影响

The effects of hyperglycemia on activation of hepatic stellate cells the expression of transforming growth factor β1 and connective tissue growth factor in the liver of rat model induced with carbon tetrachloride

目的探讨高血糖加重四氯化碳中毒大鼠肝纤维化进展的机制。方法24只SD大鼠分为对照组、高血糖组、正常血糖+四氯化碳组、高血糖+四氯化碳组,通过链脲佐菌素诱导高血糖,4周后用四氯化碳诱导肝纤维化,第9周处死。免疫组化法检测肝组织α-平滑肌肌动蛋白表达(反映肝星状细胞活化);实时RT-PCR及免疫印迹法测量肝组织转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)mRNA及蛋白表达。结果肝星状细胞活化、TGF-β1和CTGFmRNA和蛋白表达在对照组和高血糖组无明显改变,正常血糖+四氯化碳组、高血糖+四氯化碳组较对照组升高,后者较前者变化更为明显。这些改变与肝纤维化积分相平行。结论高血糖可通过诱导肝脏TGF-β1、CTGF表达以及星状细胞活化,加重四氯化碳中毒大鼠肝纤维化的程度。

Objective To investigate if hyperglycemia can affect activation of hepatic stellate cells and expression of TGF-β1 and CTGF in the normal , inflammatory and fibrotie liver of rat induced by carbon tetraehloride. Methods Normal male Sprague- Dawley rats were randomly divided into four groups： control group（ n = 6）, hyperglycemia group（ n = 5）, normal blood glucose ＋ CC14 group（ n =6）,hyperglycemia ＋ CC14 group（ n=5）. Hyperglycemia was induced by STZ（60 mg/kg）. Liver inflammation and fibrosis were induced by CC14 （40% , 2 ml/kg, biw） after hyperglycemia for four weeks. All rats were killed at week 9. TGF-β1, CTGF mRNA and protein, a-SMA in liver tissue were measured. Results There was no differences of the hepatic stellate cell activation and TGF-β1, CTGF expression between the control group and hyperglycemic group. The normal blood glucose ＋ CCl4 group and hyperglycemia ＋ CC14 group had high levels of hepatic stellate cell activation, TGF-β1, CTGF expression, especially the latter was more marked than the former. Conclusion Hyperglycemia alone may not aggravate liver fibrosis, but it might do as other liver injuring factors exist.