诱导HO-1表达延长大鼠心脏移植物存活时间  

Induction of HO-1 expression prolongs cardiac graft survival in rats

作　　者：徐涛[1] 王晓峰[1] 曲星珂[1] 叶海云[1] 张晓鹏[1] 黄晓波[1] 侯树坤[1] 

机构地区：[1]北京大学人民医院泌尿外科,北京100044

出　　处：《基础医学与临床》2006年第10期1093-1098,共6页Basic and Clinical Medicine

摘　　要：目的了解血红素加氧酶-1(HO-1)在延长异基因大鼠心脏移植物存活中的作用及其机制。方法雄性LEW(RT11)和LEW.1W(RT1u)大鼠分别作为供体和受体,受体鼠分别应用CoPPIX 5 mg/(kg.d),SnPPIX5 mg/(kg.d)。对照组及实验组均6只鼠。由移植手术前1日开始至发生排斥,比较心脏移植物存活时间,分别在移植后第5天取心脏进行HE染色及CD3、CD25、ED1和K i-67染色;并测定HO-1活性和用W estern b lot定量HO-1蛋白;进行受体脾细胞接受供体脾细胞刺激的混合淋巴细胞培养。结果对照组心脏移植物平均7 d出现排斥;应用CoPPIX诱导HO-1表达后存活时间为13.5 d,显著长于对照组(P<0.05)。而应用SnPPIX治疗后存活时间为6.5 d。对照组与SnPPIX治疗组的心脏移植物中有中等量的细胞浸润,CoPPIX治疗组移植物组织中的CD3+T细胞、CD25+细胞、巨噬细胞和增殖细胞都明显少于SnPPIX及对照组。同对照组相比,CoPPIX诱导HO-1表达明显抑制体内脾细胞增生(P<0.05),而SnPPIX无抑制。结论诱导HO-1表达能够抑制大鼠淋巴细胞的免疫活性并延长异基因心脏移植物的存活。Objective To study the effect of heme oxygenase-1 （ HO-1 ） on cardiac graft survival in rats and its mechanism. Methods Male LEW （RTll） and LEW. 1W （RTlu） rats were used as donor and recipient of heterotopic heart transplantation. Recipient rats were treated with CoPPIX [ 5 mg/（kg·d）, n=6 ], SnPPIX [ 5 mg/（ kg·d）, n = 6 ] and control （ n =6 ）. Histology, immunohistochemistry staining, HO activity assay and Western blot of HO-1 were performed using cardiac grafts. Mixed lymphocyte cultures were completed using irradiated LEW. 1W splenocytes with splenocytes derived from cardiac recipients. Grafts were excised from recipient at 5 days after transplantation. Results Induction of HO-1 with CoPPIX resulted in a significant prolongation of graft survival,the median survival time of the grafts was 13.5 days（ P 〈0. 05 ）. The median survival time of SnPPIX treatment and control group were 6. 5 and 7. 0 respectively. In the grafts of control and SnPPIX treatment group, there is evident cellular infdtration. Treatment of CoPPIX induced the cellular infiltrate of CD4^＋ , CD25^＋ , Ki67^＋ cells. CoPPIX treatment significantly suppressed donor reactive spenocyte proliferation when compared to control and SnPPIX treatment（ P 〈 0. 05 ）. Conclusion Induction of HO-1 inhibits alloreactive lymphocyte activity and prolongs cardiac graft survival in rats.

关 键 词：移植 排斥 血红素加氧酶-1 大鼠 

分 类 号：R654.2[医药卫生—外科学]