雷帕霉素联合卡托普利对大鼠同种异体血管病作用.docVIP

雷帕霉素联合卡托普利对大鼠同种异体血管病作用 　 作者：卢衡, 陈良万, 邱罕凡, 黄雪珊 【摘要】 目的 研究雷帕霉素(RPM)和卡托普利单独或联合用药对大鼠同种异体血管病(CAV)的作用。 方法 建立大鼠同种异体颈动脉移植模型,分别给予蒸馏水、卡托普利、RPM及联合用药（卡托普利+RPM）处理,在移植前和移植后8周查血清NO含量,取组织检测血管内膜厚度,免疫组织化学检测移植动脉中TGFβ1、VCAM1的表达和PCNA阳性细胞百分率及 CD4+T淋巴细胞的浸润情况。 结果 卡托普利和RPM均可减轻移植动脉血管内膜的增厚程度,联合用药组动脉血管内膜增厚程度最小。各组的血管因子表达情况和CD4＋T细胞的浸润存在差异。 结论 RPM和卡托普利均可延缓移植后CAV的发生、发展,二者联合用药效果更好。 【关键词】 雷帕霉素; 卡托普利; 心脏移植; 血管疾病; 移植,同种; 疾病模型,动物 　　ABSTRACT: Objective To investigate the effects of sirolimus or catopril and their combination on allograft angiopathy in rats. Methods The establishment of allograft model was achieved by carotid transplantation in rats. 60 rats were randomly classified into four groups according to being given different medicine: the controlled group(A), catopriltreated group (B), sirolimustreated group(C) and combinationtreated group(D). At 0, 8 weeks after transplantation the NO content in blood serum were measured and the grafts were harvested for observing the regional changes in the intimal layers by light microscopy and the expression of TGFβ1, VCAM1, PCNA% and CD4+T cells count in the allograft by immunohistochemistry. Results There was a reduced intimal thickness in both catopriltreated group and sirolimustreated group, especially in the combined treated group. The number of CD4+T cell infiltration in allograft of group B, group C and group D was less than that of group A(Plt;0.05). The NO content in serum of group B and group D was higher than that of group A(Plt;0.05). There was weak expression of TGFβ1, VCAM1 in allograft and lower PCNA(%) in group B, group C and group D than those in group A(Plt;0.05). Conclusion The prevention of catopril and sirolimus on allograft angiopathy is significant and the effect was most obvious when drugs were used combinedly. 　　KEY WORDS: catopril; sirolimus; allograft angiopathy; rats 　　心脏移植后同种异体血管病(CAV)是影响心脏移植病人长期存活的一个主要原因。CAV病变呈现多样性,既有向心性纤维内膜增生的改变,也有类似于普通冠心病的偏心性粥样斑块形成[1]。笔者应用大鼠同种异体颈动脉移植模型,对雷帕霉素(RPM)和ACEI类药物卡托普利在移植物慢性血管病变中的作用进行研究,报道