摘要
目的:探讨促红细胞生成素(促红素)预处理对大鼠心肌缺血再灌注损伤的保护作用及其可能机制。方法:40只 SD 大鼠随机分为5组(每组8只):假手术组、模型组、促红素组、锌原卟啉组、促红素+锌原卟啉组,建立大鼠心肌缺血再灌注损伤模型,缺血45 min,再灌注180 min,采用免疫组织化学及逆转录—聚合酶链反应分别测定大鼠心肌组织单核细胞趋化蛋白-1(MCP-1)、血红素氧合酶-1(HO-1)和 mRNA 的表达,电镜观察心肌超微结构的病理学改变。结果:与假手术组比,其余4组缺血再灌注心肌中 MCP-1、HO-1免疫组化平均光密度值和逆转录—聚合酶链反应mRNA 表达增多(P 均<0.01),差异有统计学意义;与模型组比,促红素预处理能明显上调 HO-1 mRNA 表达,并降低缺血再灌注心肌 MCP-1 mRNA 表达(P 均<0.05～0.01),差异有统计学意义,同时改善心肌超微结构的损伤,使用锌原卟啉后,促红素预处理的保护作朋消失(P>0.05);与促红素组比较,锌原卟啉组和促红素+锌原卟啉组大鼠心肌中 HO-1mRNA 表达均降低,MCP-1 mRNA 表达均增高(P<0.05～0.01),差异有统计学意义,且心肌超微结构损伤加重。结论:促红素预处理可能通过增强 HO-1表达并降低 MCP-1表达,改善心肌超微结构的损伤,对大鼠心肌缺血再灌注损伤产生保护作用。
Objective：To explore the protective effect and possible mechanism of the pretreatment with erythropoietin in rats with the myocardial ischemia-reperfusion（IR） injury. Methods：A total of 40 male Sprague-Dawley rats were randomly divided into 5 groups：sham operation group （F group）, operation group（ O group ）, erythropoietin group （E group ）, zinc protoporphyrin group （Z group ）, and erythropoietin ＋ zinc protoporphyrin group（ ZE group）. There were 8 rats in each group. The rat model of myocardial IR injury was reproduced by the ligation of left anterior descending coronary artery（LAD） for 45 minutes followed by 180 minutes of reperfusion. The LAD of F group was not clamped. The E group was pretreated with the intraperitoneal injection of erythropoietin（4 000 U/Kg）24hours before IR,and the Z group with the intraperitoneal injection of zinc protoporphyrin （20 μmol/kg）12 hours before IR, and the ZE group with erythropoietin（4 000 U/Kg）24 hours before IR combined with zinc protoporphyrin（ 20 μmol/kg）12 hours before IR. The expression of MCP-1 and HO-1 protein and mRNA in left ventricle was detected by immunohistochemistry and RT-PCR. The changes of myocardial ultrastructurc were observed with transmission electronmicroscopy（TEM）. Results：Compared with F group, the expression of MCP-1 and HO-1 mRNA increased significantly in other groups （P 〈 0. 01 ） ;compared with O group ,erythropoietin could significantly increase the expression of HO-1 and decrease the expression of MCP-1 induced by IR（P 〈 0. 05 - 0. 01 ）, and markedly decrease the injury of the myocardial uhrastructure caused by IR. The protective effects of erythropoietin were prevented by zinc protoporphyrin （ P 〉 0.05 ）. Compared with E group, the expression of HO-1 decreased and the expression of MCP-1 increased significantly in Z and ZE groups （ P 〈 0. 05 - 0. 01 ） , and the injury of myocardial ultrastructure was aggravated. Conclusion： The pretreatment of erythropoietin could protect cardiomyocyte against ischemia-reperfusion injury, probably through up-regulating HO-1 expression and de-regulating MCP-1 expression.
出处
《中国循环杂志》
CSCD
北大核心
2008年第4期306-309,共4页
Chinese Circulation Journal
