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供肝丹参多酚酸盐预处理减轻受体大鼠肝移植术后胆道损伤
宋少华1△,郭闻渊1△,傅志仁1,傅宏1*,沈筱芸2,刘芳1,王正昕1,丁国善1
0
(1.第二军医大学长征医院器官移植中心,上海 200003;2.第二军医大学基础部免疫学教研室,上海 200433)
摘要:
目的观察丹参多酚酸盐预处理供肝对受体大鼠肝移植术后胆道损伤的影响,探讨其可能的作用机制。方法根据供体肝脏保存方法,受体大鼠随机分为UW液组、丹参多酚酸盐预处理组(UW液+0.4 mg/ml丹参多酚酸盐)、生理盐水对照组(UW液+等量生理盐水)。大鼠行胆道持续外引流肝动脉化原位肝移植,观察移植术后1、6、24 h胆汁流量及胆汁酸盐分泌量。大鼠行肝动脉化大鼠原位肝移植,移植术后2周检测各组大鼠血清碱性磷酸酶、胆汁酸盐及总胆红素水平,观察胆道并发症发生率;采用实时荧光定量PCR、蛋白印迹法分别检测肝脏移植物内胆汁酸盐输出泵(bile salt export pump,BSEP)基因及蛋白的表达。结果与UW液组及生理盐水对照组相比,丹参多酚酸盐预处理组大鼠术后早期胆汁流量及胆汁酸盐分泌量明显增加 (P<0.05);术后2周血清碱性磷酸酶、胆汁酸盐及总胆红素水平明显降低(P<0.05),胆汁淤积等胆道并发症发生率明显降低 (P<0.01);肝脏移植物内BSEP mRNA及蛋白表达均升高(P<0.05)。结论UW液内加入丹参多酚酸盐保存供肝可明显减轻受体大鼠肝移植术后胆道损伤,降低术后胆道并发症的发生,可能与其促进移植肝内BSEP表达有关。
关键词:  丹参多酚酸盐  移植预处理  肝移植  胆道损伤
DOI:10.3724/SP.J.1008.2010.0136
投稿时间:2009-09-24修订日期:2010-01-07
基金项目:上海市卫生局青年科研项目(2008Y085).
Pretreatment of donor liver with salvianolate reduces biliary injury in rats after liver transplantation
SONG Shao-hua1△, GUO Wen-yuan1△,FU Zhi-ren1,FU Hong1*,SHEN Xiao-yun2,LIU Fang1, WANG Zheng-xin1, DING Guo-shan1
(1.Organ Transplantation Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China;2.Department of Immunology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433,China)
Abstract:
ObjectiveTo evaluate the effect of pretreating donor liver with salvianolate on biliary injury after orthotopic liver transplantation (OLT) in rats,and to discuss the underlying mechanisms. MethodsAccording to the preservation solutions of the liver grafts, the recipients rats were allocated in three groups: UW solution group, salvianolate group (UW solution + 0.4 mg/ml salvianolate), and saline group (UW solution + saline). In experiment 1, the recipient rats underwent arterialized OLT with biliary extra-drainage, and the bile flow and bile salt secretion were recorded at 1, 6, and 24 h post-transplantation. In experiment 2, the recipient rats underwent arterialized OLT, and the serum alkaline phosphatase, bile salt, total bilirubin, and the incidence of biliary complications were examined at 2 weeks post-transplantation. Meanwhile, the mRNA and protein expression of bile salt export pump (BSEP) in the liver samples were also detected using real-time RT-PCR and Western blotting analysis,respectively. ResultsCompared with the UW solution and saline groups, salvianolate group exhibited significantly increased bile flow and bile salt secretion at 1, 6, and 24 h post-transplantation (P<0.05). At 2 weeks post-transplantation, salvianolate group had significantly lower serum alkaline phosphatase, bile salt, total bilirubin(P<0.05), and incidence of biliary complications(P<0.01), and significantly higher expression of BSEP mRNA and protein compared with the other two groups (P<0.05). ConclusionSalvianolate addition in UW preservation solution can ameliorate biliary injury and reduce the incidence of biliary complications after OLT in rats, which might be associated with increased expression of BSEP in liver graft.
Key words:  salvianolate  transplantation conditioning  liver transplantation  biliary injuries