摘要
目的:探讨二甲基亚硝胺(DMN)诱发大鼠肝纤维化库普弗细胞与肝星状细胞的分布及其意义。方法:选取40只Wistar雄性大鼠连续4周腹腔注射10 g/L DMN制备肝纤维化模型。采用随机数字表法分为模型组(n=20)与正常组(n=20),两组均应用DMN进行肝纤维化造模。采用Reiman法测定大鼠第4周和第7周ALT、AST水平,免疫组化法测定两组大鼠库普弗细胞与肝星状细胞标志物ED1与α-SMA分布情况,收集并分析两组肝/体质量比、肝组织病理变化、胶原纤维面密度。结果:模型组第4周和第7周ALT、AST、面密度水平均高于正常组,差异均有统计学意义(P<0.05);模型组第4周和第7周总蛋白(TP)、肝/体质量比水平均低于正常组,差异均有统计学意义(P<0.05);两组第4周与第7周肝/体质量组内比较,差异均无统计学意义(P=0.11);模型组第4周和第7周光镜下可见ED1、α-SMA阳性细胞数量较多,主要分布于增生的纤维组织及纤维间隔弥漫部位。结论:DMN可导致大鼠肝功能障碍及弥漫肝硬化。大鼠肝纤维化模型的库普弗细胞可激活、活化肝星状细胞。
Objective:To investigate the distribution and significance of Kupffer cells and hepatic stellate cells in rat hepatic fibrosis induced by dimethylnitrosamine(DMN).Method:40 Wistar male rats were intraperitoneally injected with 10 g/L DMN for 4 weeks to prepare the hepatic fibrosis model.All rats were divided into model group(n=20)and normal group(n=20)according to the random number table method.DMN was used to establish liver fibrosis model in both groups.The levels of ALT and AST in two groups were measured by Reiman method at the 4 th and 7 th week.The distribution of ED1 and alpha-SMA markers in Kupffer cells and hepatic stellate cells of rats were determined by immunohistochemistry.The liver/body mass ratio,pathological changes of liver tissue and surface density of collagen fibers in two groups were collected and analyzed.Result:The levels of ALT,AST and area density in the model group were higher than those in the normal group at the 4 th and 7 th week(P<0.05).The levels of total protein(TP)and liver/body mass ratio in the model group were lower than those in the normal group at the 4 th and 7 th week(P<0.05).There was no significant difference in liver/body mass time between the two groups at the 4 th and 7 th week(P=0.11).The number of ED1 and α-SMA positive cells in the model group were higher at the 4 th and 7 th week under light microscope.These were mainly distributed in the proliferative fibrous tissue and the diffuse part of the fibrous septum.Conclusion:DMN can cause liver dysfunction and diffuse cirrhosis in rats.Kupffer cells in rat hepatic fibrosis model can activate and activate hepatic stellate cells.
引文
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