CP-690550抑制同种异基因小鼠心脏移植后急性排斥反应  

Effect of CP-690550 on Acute Rejection for Allogeneic Heart Transplanting in Mice

作　　者：明飞[1] 向道康[1] 

机构地区：[1]贵州省人民医院心外科,贵阳550002

出　　处：《贵州医药》2009年第4期299-301,共3页Guizhou Medical Journal

基　　金：贵州省优秀科教人才省长基金(2007第64号)

摘　　要：目的观察心脏移植术后小鼠使用CP-690550对移植心脏信号转导和转录活化因子3(STAT3)及TH1型细胞因子IL-12的含量的影响,从而探讨CP-690550抗急性排斥反应的作用机制。方法建立同种异基因小鼠颈部异位心脏移植模型,随机分为对照组(n=6)和干预组(n=6)。干预组小鼠手术当天及术后给予CP-690550口服(10mg/kg/d)至观察终止,记录移植心脏存活时间,取移植心脏标本,以western blotting法检测标本STAT3表达,以ELISA法检测标本IL-12;对照组除不口服CP-690550外,其它情况同干预组。结果CP-690550干预组移植心脏存活时间(4.66±0.52)d,明显长于对照组(3.00±0.63)d(P<0.01),HE染色对照组心肌淋巴细胞浸润情况较干预组严重;STAT3及IL-12在移植心脏均有明显表达,且两组含量比较有统计学意义(P<0.01)。结论CP-690550通过调控JAK激酶3(Janus Kinase 3)-STAT3信号通路,抑制树突状细胞(DC)成熟及IL-12的释放,诱导T细胞无能,引起免疫耐受而实现抗急性排斥反应。Objective To investigate the express of STAT3 and IL-12 on transplanted hearts and explore the mechanism of CP-690550 on the acute rejection in mice. Methods Established cervical heterotopic and allogeneic heart transplanting models in mice were divided into test group （n= 6） and control group （n=6）. The test group was administered CP-690550 （po. 10mg/kg/day） after heart transplantation till the observed termination, the other conditions were same in two groups. STAT3 content was detected by the western blotting method and IL-12 content was detected by the ELISA meth od. Results The transplanted hearts＇ living duration of test group （4. 66±0. 52）d was longer than in control group （3. 00±0. 63）d. The expression of STAT3 and IL-12 contents were significantly lower in the test group than that in the control group （P〈0. 01）. Conclusion CP-690550 can obviously extend living duration of transplanted hearts and relieve the acute rejection. These effects maybe work through following mechanisms： Through regulating JAK3-STAT3 signal channel, to restrain dendritic cells＇ maturation, reducing IL-12＇s release, and induce T cells＇ immune tolerance.

关 键 词：心脏移植 急性排斥反应 CP-690550 小鼠 STAT3 IL-12 

分 类 号：R654[医药卫生—外科学]