小半夏加茯苓汤对小鼠移植心存活时间的延长效果研究  

Xiaobanxia Plus Fulin Decoction Prolonged the Survival of Fully Allogeneic Cardiac Grafts in Mice

作　　者：刘洋[1] 殷恩智 郝思雨[1] 田江天[1] 杨金儒 

机构地区：[1]哈尔滨医科大学附属第二医院,黑龙江哈尔滨150081 [2]哈药集团制药六厂,黑龙江哈尔滨150081

出　　处：《现代生物医学进展》2016年第27期5210-5213,共4页Progress in Modern Biomedicine

基　　金：黑龙江省博士后基金项目(LBH-Z15161)

摘　　要：目的:探讨小半夏加茯苓汤对小鼠心脏移植模型中移植心存活时间的延长效果及作用机制。方法:将接受过腹腔心脏移植手术的小鼠分为实验组和对照组,自移植手术当日起至术后7天,每日经口给药,通过腹部触诊判断移植心脏跳动情况,移植术后30日,取部分小鼠移植心脏进行病理检查,取脾细胞进行淋巴细胞培养,并检测培养液中白细胞介素(IL)-2、IL-4、IL-10和干扰素(IFN)-γ的浓度。取移植心脏存活时间超过30天的小鼠脾脏,通过流式细胞术检测调节性T细胞(Regulatory Tcells,Tregs)的含量。结果:与对照组相比,实验组的移植心存活时间明显延长(P<0.01),心脏病理切片结果提示实验组的心脏血管病变受到了抑制,脾细胞培养液中IL-2和IFN-γ浓度明显降低,而IL-4和IL-10的浓度升高,脾细胞CD4阳性细胞中CD25和Foxp3均阳性的细胞含量明显高于对照组中同类细胞含量。结论:小半夏加茯苓汤可以显著延长小鼠移植心脏的存活时间,可能与其诱导调节T细胞的产生、改变受体小鼠体内Th-1和Th-2细胞因子的平衡及抑制IL-2、IFN-γ减轻心脏损伤有关。Objective： Xiaobanxia plus Fulin decoction is well known as an herbal medicine with few side effects to treat vomiting, nausea, acute and chronic gastritis, and hyperemesis of pregnancy in Japan. In this study, we performed fully allogeneic cardiac grafts in mice to investigate the effect of Xiaobanxia plus Fulin decoction on alloimmune responses. Methods： CBA（H2k） mice underwent transplantation of a C57BL/6（H2b） heart and received oral administration of 2 g/kg per day of Xiaobanxia plus Fulin decoction from the day of operation until 7 days afterward. Histologic and cell proliferation studies, flow cytometry analyses and cytokine measurements were also performed. Flow cytometry study showed Xiaobanxia plus Fulin decoction-treated mice had an increased CD4＋,CD25＋,Foxp3＋cell population. Results： Compared to untreated CBA mice rejected C57BL/6 hearts acutely（median survival time [MST], 8days）, MST of allografts from Xiaobanxia plus Fulin decoction-treated mice was prolonged（MST, 58 days）. Histologic examinations of cardiac allografts obtained 30 days after transplantation showed cell infiltrated but significantly preserved structure with a few myocardial injuries in transplant recipients given Xiaobanxia plus Fulin decoction. Cell proliferation showed that interleukin-2（IL-2） and interferon-γ（IFN-γ） were inhibited in Xiaobanxia plus Fulin decoction-treated mice, whereas IL-4 and IL-10 were increased. Evidence of generation of regulatory cells in CBA allograft recipients treated with Xiaobanxia plus Fulin decoction. CD4, CD25, and Foxp3 expression in splenocytes, as determined by flow cytometry. Conclusions： In summary, Xiaobanxia plus Fulin decoction could induce hyporesponsiveness of fully MHC-mismatched cardiac allografts. The mechanism is Xiaobanxia plus Fulin decoction could generate regulatory cells,change the balance between Th-1 and Th-2 cytokines secretion and suppress IL-2 and IFN-γ.

关 键 词：小半夏加茯苓汤 心脏移植 免疫抑制 

分 类 号：R-33[医药卫生] R285.5