补体旁路途径的激活在肝再生过程中作用的研究  

A role of the alternative pathway of complement in liver regeneration

作　　者：李丹[1,2] 姜立[1] 程琪[1] 窦磊[1] 陈孝平[1] 何松青[3] 

机构地区：[1]华中科技大学同济医学院附属同济医院肝脏外科中心,武汉430030 [2]天津医科大学南开临床学院全国中西医结合胆胰疾病医疗中心 [3]桂林医学院附属医院肝胆胰外科

出　　处：《腹部外科》2010年第4期240-242,共3页Journal of Abdominal Surgery

基　　金：国家自然科学基金(30972797);湖北省自然科学基金(2008CDB146)

摘　　要：目的探讨在小鼠肝切除术后补体旁路途径的激活在肝再生过程中的作用。方法将实验动物分为3组:A组野生型C57BL/6小鼠行假手术,B组野生型C57BL/6小鼠行70%肝部分切除术(PHx)和C组补体旁路途径激活的关键蛋白-B因子缺陷(fB-/-)小鼠行70%PHx,评估小鼠术后肝脏损伤及肝再生情况。结果与A组比较,B组术后48h血清ALT和T-BIL水平均显著增高(P<0.01),而C组更分别比B组高出2.2倍和3倍(P<0.01)。术后48h肝脏组织经HE染色发现,A组无明显病理性改变;B组肝脏呈轻度脂肪变性,坏死少见;C组肝脏组织为中重度脂肪变性,坏死明显。通过采用肝脏重量的重建、BrdU结合率及有丝分裂指数来综合评估肝脏的再生能力,结果与A、B两组相比,C组小鼠肝脏的再生功能受到了严重损害。免疫组织化学染色检测补体C3的沉积,A组为阴性,B组为强阳性,C组为弱阳性。生存率分析,野生型小鼠术后7d存活率为100%,而fB-/-小鼠仅为58.33%,两组间差异有统计学意义(P<0.01)。结论小鼠行70%PHx后可通过旁路途径激活补体系统,并参与肝脏再生,阻断补体旁路途径的激活会严重抑制肝脏的再生功能。Objective To explore the role of the alternative pathway of complement in liver re- generation. Methods The animals were divided into 3 groups：The animals in group A were subjected to sham surgery,and those in group B（littermate C57BL/6 wild type mice） and group C（fB-/- mice） received 70 % PHx. Liver injury and liver regeneration were assessed after operation. Results At the 48th h after 70 % PHx, levels of both ALT and T-BIL were significantly higher in group B than in group A（P〈（0. 01 ）. However, there was a much more significant increase in group C, with 2. 2 and 3. 0 fold increased over wild type mice, respectively（P〈0. 01 ）. There were no pathological changes ob- served in H＆E-stained liver sections in group A. In group B, mild steatosis developed 48 h but only rarely necrosis was detected. In contrast there was moderate to severe steatosis in group C and an in- creased incidence of necrosis. Hepatic proliferative response was evaluated by BrdU incorporation, mitotic index（MI） and restitution of liver weight following 70 % PHx,and all of the three measures sug- gested that liver regeneration was severely impaired in group C compared to groups A and B. At the 48th h after PHx,no staining for C3 was observed in group A. In contrast,C3 deposition was evident in group B. However, only weak C3 staining was detected in group C at the 48th h after PHx. The 7-day survival rate for wild type mice after 70 % PHx was 100% compared to less than 58. 33 % for fB-/ mice（P〈0. 01）. Conclusion Complement can be activated via its amplification by the alternative pathways in the liver after PHx, and the selective inhibition of this pathway results in severe damage to the liver regeneration after PHx.

关 键 词：肝再生 补体C3-C5转化酶类 旁路途径 肝切除 

分 类 号：R561.3[医药卫生—呼吸系统]