促红细胞生成素衍生肽对小鼠心肌缺血再灌注损伤的作用及机制研究  

Effect and Mechanism of Helix B Surface Peptide on Reducing Myocardial Ischemia Reperfusion Injury in Experimental Mice

作　　者：游伟[1] 刘映峰[1] 缪绯[1] 林霖[1] 张杰波 王龙[1] 朱凯[1] 林湧栾[1] 刘芃[1] 

机构地区：[1]南方医科大学珠江医院心内科,广东省广州市510282

出　　处：《中国循环杂志》2015年第10期996-999,共4页Chinese Circulation Journal

基　　金：广东省自然科学基金资助项目(2015A030313238);广东省医学科学技术研究基金资助项目(B2015023)

摘　　要：目的:探讨促红细胞生成素衍生肽(HBSP)对小鼠心肌缺血再灌注损伤(MIRI)的作用及其机制。方法:64只雄性ICR小鼠随机分成四组,每组16只:假手术组、MIRI组、HBSP组、HBSP+胞外信号调节蛋白激酶1/2(ERK1/2)特异性阻断剂(PD98059)组(HBSP+PD98059组)。通过结扎小鼠冠状动脉左前降支45 min后解除结扎线建立小鼠心肌缺血再灌注模型,HBSP于再灌注前5 min给药。再灌注2 h后,用2,3,5-氯化三苯基四氮唑(TTC)和伊文氏蓝(EB)双染色法检测小鼠心肌梗死面积,原位缺口末端标记法(TUNEL法)检测心肌细胞凋亡率,蛋白免疫印迹(Western blot)法检测ERK1/2和磷酸化ERK1/2的表达。结果:缺血再灌注2 h后,与MIRI组相比,HBSP组心肌梗死面积显著缩小(P<0.05),心肌细胞凋亡率降低(P<0.05),ERK1/2的磷酸化水平升高(P<0.05),差异均有统计学意义。与HBSP组相比,HBSP+PD98059组的ERK1/2磷酸化水平明显降低,心肌细胞凋亡率升高,心肌梗死面积明显增大(P均<0.05),差异均有统计学意义。结论:HBSP可通过抑制心肌细胞凋亡,缩小心肌梗死面积,在小鼠心肌缺血再灌注损伤中发挥保护作用,其机制与ERKl/2通路的激活有关。Objective： To investigate the effect and mechanism of helix B surface peptide （HBSP） on myocardial ischemia reperfusion injury （MIRI） in experimental mice. Methods： The MIRI model was established by ligation of anterior descending coronary artery of the mice for 45 min and followed by corresponding treatment at 5 min before reperfusion. A total of 64 male ICR mice were randomly assigned to 4 group： ①Sham group, ①MIRI group, the mice received normal saline at 5 min before reperfusion, ③HBSP group, MIRI mice received HBSP at 5 min before reperfusion and ④HBSP＋PD98059 group, MIRI mice received PD98059 （a specific blocker of ERK1/2） at 20 min before reperfusion and followed by HBSP at 5 min before reperfusion, n=16 in each group, all animals were treated for 2 hours. The area of myocardial infarction （MI） was detected by TTC-EB double staining method, the myocardial apoptosis rate was examined by TUNEL method, the levels of protein expression of ERK1/2 and phosphorylation of ERK1/2 were measured by Western blot analysis. Results： Compared with MIRI group, HBSP group presented decreased MI area, decreased myocardial apoptosis rate and increased phopsphorylation level of ERK1/2, all P〈0.05. Compared with HBSP group, HBSP＋PD98059 group showed decreased phopsphorylation level of ERK 1/2, increased myocardial apoptosis rate and increased MI area, all P〈0.05. Conclusion： HBSP may reduce the MI area via inhibiting myocardial apoptosis and therefore, protecting the experimental mice from MIRI; the mechanism might be related to the activation of ERK1/2 pathway.

关 键 词：缺血再灌注损伤 促红细胞生成素衍生肽 细胞凋亡 

分 类 号：R54[医药卫生—心血管疾病]