瘦素在小鼠日本血吸虫病肝纤维化中的作用及其机制  

The molecular mechanisms of leptin in liver fibrosis induced by schistosoma japonicurn infection in mice

作　　者：刘忠臣[1] 牛丽文[2] 杨镇[3] 陶强[2] 冯亮[2] 邓庆强[2] 

机构地区：[1]厦门大学附属中山医院胃肠外科,361004 [2]江西省儿童医院普外科 [3]华中科技大学同济医学院附属同济医院普外科

出　　处：《中华实验外科杂志》2009年第6期739-741,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察小鼠感染日本血吸虫后不同时期肝脏瘦素和磷脂酰肌醇-3激酶（P13K）蛋白在日本血吸虫病肝纤维化形成中的动态表达，探讨PI3K通路在瘦素促日本血吸虫病肝纤维化过程中的作用。方法日本血吸虫尾蚴皮肤敷贴法感染小鼠构建日本血吸虫病肝纤维化模型，于感染后2、4、6、8、12、16、20、24周取肝标本。免疫组织化学SP法动态观察瘦素蛋白表达；Western blot法分析P13K蛋白动态表达。结果瘦素阳性表达位于胶原纤维沉积处，随病程进展而增加；模型组P13K在感染4周开始表达，随病程进展逐渐增高，持续至24周。相关分析表明，瘦素与肝胶原含量（r=0．758，P〈0．01）及肝纤维化程度均呈正相关（r=0．823，P〈0．01）；P13K与瘦素（r=0．882，P〈0．01）、肝胶原含量（r=0．889，P〈0．01）及肝纤维化程度（r=0．807，P〈0．01）均呈正相关。结论瘦素通过增强PI3K磷酸化，而促进胶原合成，进而促进日本血吸虫病肝纤维化形成，PI3K通路在该过程中发挥重要作用。Objective To observe the dynamic changes in leptin and phosphatidylinositol 3-kinase （PI3K） protein expression in mice liver fibrosis induced by schistosoma Japonica infection at different periods, and to investigate the roles of PI3 K pathway in liver fibrosis induced by schistosoma japonicum infection in mice by leptin. Methods Mice infected with schistosoma Japonica cereariae percutaneously served as animal models of liver fibrosis, and liver biopsies were done at different time points after infec- tion. Immunohistochemistry for leptin was performed to observe the dynamic changes by SP technique. PI3K protein dynamic expression was detected by Western blot. Results Leptin positive cells were localized in collagen fibers. The leptin positive cells were increased gradually with course of diseases. PI3K protein expression began at the 4th week after infection, increased progressively and persisted at the 24th week after infection. There was a positive correlation between leptin protein expression and collagen content （ r = 0.758,P 〈 0.01 ） or degree of liver fibrosis （r = 0.823, P 〈 0.01 ）. Similarly, there was a positive correla- tion between PI3K protein and leptin （ r = 0. 882 ,P 〈 0.01 ） or collagen content （ r = 0. 889 ,P 〈 0.01 ） or degree of liver fibrosis （ r = 0. 807, P 〈 0.01 ）. Conclusion Leptin promoted collagen protein production by stimulating PI3K phosphorylation in the progress of liver fibrogenesis of mice with Schistosomiasis Japonica,and PI3K pathway plays an important role in the process.

关 键 词：日本血吸虫病 肝纤维化 瘦素 磷脂酰肌醇-3激酶 

分 类 号：R686[医药卫生—骨科学]