摘要
目的 探讨后处理减轻缺血/再灌注所致的心肌损伤效应是否与低氧诱导因子-1α (HIF-1α)及其下游通路有关.方法 建立大鼠心肌缺血/再灌注及后处理模型,检测心肌组织中HIF-1α及其下游基因诱导性一氧化氮合酶(iNOS)的表达情况及cGMP的含量.结果 后处理缩小缺血/再灌注所致的心梗面积[(27.30±4.16)%比 (36.00±5.29)%,P<0.01],减少心肌细胞凋亡(Caspase 3比活性:(1.85±0.50)比(3.79±0.64),P<0.01),上调心肌组织中HIF-1α表达[(5.76±0.55) 比(2.85±0.13),P<0.01)的同时,提高了iNOS的表达及其cGMP的含量.预先给予HIF-1α脯氨酸羟化酶抑制剂DMOG使后处理心肌组织中HIF-1α表达进一步上调后,iNOS的表达及cGMP含量随之增加,同时后处理减轻心肌损伤的效应[心梗面积:(17.95±2.00)% 比 (27.30±4.16)%,P<0.01; Caspase3比活性:0.43±0.13比1.85±0.50,P<0.01]也进一步增强.结论 后处理减轻缺血/再灌注所致心肌损伤的效应可能与其激活心肌组织中HIF-1α-iNOS-cGMP通路有关.
Objective To explore whether the cardioprotection of postconditioning against ischemia/reperfu- sion injury is related to the activation of the HIF-1a-iNOS-eGMP pathway. Methods Adult male Wistar rats underwent the left anterior descending coronary artery 30 min myocardial ischemia (I) and 180 rain reperfusion (R) with or without postconditioning (PostC, i.e., 3 cycles of 10 s R/I after onset of the reperfusion). Myocardial damage was evaluated by infarct size and Caspase 3 activity. The expressions of HIF-1a and iNOS were examined by Western blot and real time-PCR. The content of cGMP was detected by the method of radioimmunology. Results Postconditioning attenuated myocardial infarct size [ (27.30±4.16)% vs ( 36.00±5.29 )%, P〈0.01 ] and the activity of Caspase 3 (1.85±0.50 vs 3.79±0.64, P〈0.01 ), and simultaneously increased the expression of HIF-1a (5.76± 0.55 vs 2.85±0.13, P〈0.01) compared with I/R group. Meanwhile, the expression of iNOS and the content of cGMP were also increased by postconditioning. After upregulation of HIF-1a-iNOS-cGMP by DMOG, the cardioprotective effects of postconditioning were further enhanced, including the decrease of infarct size [ (17.95±2.0)% vs(27.3±4.16)%, P〈0.01 ] and activity of Caspase 3 (0.43±0.13 vs 1.85±0.50, P〈0.01 ). Conclusion The cardioprotection of postconditioning may be related to the activation of the pathway of HIF-1a-iNOS-cGMP.
出处
《中国心血管病研究》
CAS
2011年第6期435-439,共5页
Chinese Journal of Cardiovascular Research
基金
基金项目:山西省高等学校优秀青年学术带头人支持计划(2008)资助项目