二甲基亚硝胺诱发大鼠肝纤维化模型中库普弗细胞与星状细胞的分布  

Distribution of Kupffer Cells and hepatic stellate cells in dimethylnitr- osamine-induced liver fibrosis in rats

作　　者：朴金花[1] 金京顺[1] 崔京淑[1] 朴东明[1] 

机构地区：[1]延边大学医院病理科,吉林省延吉市133000

出　　处：《世界华人消化杂志》2005年第17期2138-2141,共4页World Chinese Journal of Digestology

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(kupffercell,KC)与肝星状细胞(hepaticstellatecell,HSC)的分布及意义.方法:用10g/LDMN腹腔注射4wk制备大鼠肝纤维化模型,实验第4、7周末检测大鼠血清ALT、AST活性及总蛋白(totalproteins,TP)含量,测定肝/体质量比及肝组织胶原纤维的面密度、观察肝组织的病理变化,免疫组化采用SP法观察KC和HSC标志物ED1及α-SMA的表达及分布.结果:第4周模型组与正常组比较血清ALT、AST活性显著升高(P<0.01),TP含量和肝/体质量比明显下降(P<0.01),肝组织内胶原纤维面密度明显升高,大部分形成弥漫性肝硬化;第7周模型组除了血清TP含量无变化外ALT、AST活性仍维持较高水平,并维持肝硬化的特点.免疫组化染色第4、7周模型组ED1和α-SMA阳性细胞数量明显增加,两种细胞分布的部位相同,主要在增生的纤维组织及纤维间隔弥漫分布,在肝实质内少量散在分布.结论:DMN引起大鼠肝功能明显障碍,大部分形成弥漫肝硬化,KC与HS的分布表明KC与激活、活化HSC密切相关.AIM： To investigate the distribution and significance of Kupffer cells （KCs） and hepatic stellate cells （HSCs） in dimethylnitrosamine（DMN）-induced liver fibrosis in rats. METHODS： Rat liver fibrosis was induced by peritoneal injection of DMN（10 g/L）for 4 wk. The activities of serum alanine transaminase（ALT）, aspartate transaminase（AST）, the contents of total proteins（I-P）, the ratio of liver/body weight and the area density of collagenous fiber were examined 4 and 7 wk after injection. Meanwhile, the pathological changes of the liver tissues were observed under light microscope. The expression of ED1 and α-smooth muscle actin（α-SMA） were detected by immunohistochemical SP method. RESULTS： Compared with those in the control group, the levels of ALT and AST were significantly elevated 4 and 7 wk after injection（4 wk：1201.91±215.04, 5741.15± 1000.20 nkat/L vs 398.91±106.35, 1365.27±435.09 nkat/L, P 〈0.01; 7 wk： 745.15±413.42, 2355.47±1418.62 nkat/L vs 289.72±43.01, 1018.54±215.04 nkat/L, P 〈0.05）. TP content was significantly decreased 4 wk after injection （50.32±9.81 g/L vs 69.67±6.09 g/L, P 〈0.01）, but returned to normal after 7 wk. The ratio of liver/body weight was decreased（4 wk： 2.156±0.539% vs 2.950± 0.147% P 〈0.01 ; 7 wk： 2.250±0.638% vs 2.863±0.158%, P 〈0.01）, but the area density of collagenous fiber was increased 4 and 7 wk after injection （9.90±1.93% vs 1.27±0.28%, P 〈0.01; 9.20±0.97% vs 1.46±0.67%, P 〈0.01）. Diffuse cirrhosis was observed in most model rats after 4 wk and it was still significant after 7 wk. The ED1 and α-SMA positive cells aggregated prominently in the fibrotic tissue and septa in the model rats. CONCLUSION： DMN induces obviously liver disfunction and diffuse cirrhosis in rats, and KCs are closely associated with the activation of HSCs.

关 键 词：二甲基亚硝胺 肝硬化 大鼠 肝星状细胞 库普弗细胞 

分 类 号：R575.2[医药卫生—消化系统]