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促红细胞生成素衍生肽抑制缺血/再灌注损伤诱导的大鼠心肌细胞凋亡

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第3期
页码:
327-332
栏目:
基础研究
出版日期:
2013-06-25

文章信息/Info

Title:
Helix B surface peptide is cardioprotective through inhibition on myocardial apoptosis induced by ischemia/reperfusion injury
作者:
蒋 娜; 叶 瑾; 党晶艺; 左惠荣; 张荣庆; 司 瑞; 郭文怡
(第四军医大学西京医院心内科，陕西 西安 710032)
Author(s):
JIANG Na;  YE Jin;  DANG Jingyi;  ZUO Huirong;  ZHANG Rongqing;  SI Rui;  GUO Wenyi
(Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
促红细胞生成素; 多肽; 缺血/再灌注; 细胞凋亡; 大鼠
Keywords:
erythropoietin;  polypeptide;  ischemia/reperfusion;  apoptosis;  cardiomyocyte
分类号:
R392.12
DOI:
-
文献标识码:
A
摘要:
目的:探讨促红细胞生成素（erythropoietin，EPO）衍生肽又称螺旋B表面肽（helix B surface peptide，HBSP）在大鼠心肌缺血/再灌注损伤(I/RI)中的拮抗作用及其机制。方法:82只200~250 g雄性SD大鼠随机分为假手术(Sham)组（n=18）、缺血/再灌注(I/R)组（n=18）、EPO组（n=18）、HBSP组（n=18）及HBSP+LY294002（PI3k特异性抑制剂）组（n=10）。于灌注前5 min，于EPO组及HBSP组大鼠的尾静脉分别注射生理盐水重组人EPO(rhEPO；3 000 U/kg，4 ml/kg)及生理盐水HBSP (60 μg/kg，4 ml/kg )。颈动脉插管检测血流动力学指标，采用小动物超声分别检测24 h、1周后大鼠心功能。用TTCEB双染测定梗死面积，Western blot法检测心肌组织蛋白激酶B（Akt）和磷酸化Akt的表达。用TUNEL法检测心肌细胞凋亡。结果:与I/R组相比，EPO组和HBSP组再灌注后大鼠心脏左室收缩压（LVSP）、左室内压最大上升速率（+dp/dtmax）以及最大下降速率（-dp/dtmax）明显改善（P<0.05），左室射血分数［LVEF(%)］、室间隔厚度（IVSS）及左室短轴缩短率［FS(%)］显著增加（P<0.05），同时心肌梗死面积明显缩小（P< 0.05），心肌细胞凋亡显著减少（P<0.05）；HBSP组Akt磷酸化水平显著提高（P<0.05）。HBSP+LY294002组与HBSP组相比，Akt磷酸化水平明显降低，心肌细胞凋亡指数显著增高（P<0.05）。HBSP组与EPO组间各项指标均无显著差别。结论:HBSP能够显著抑制I/RI诱导的大鼠心肌细胞凋亡, 减少梗死面积，明显改善心功能，其保护作用可能与激活PI3K-Akt通路有关。
Abstract:
AIM:To observe the protective effects and mechanism of Helix B surface peptide (HBSP) in rat myocardial ischemia/reperfusion injury. METHODS: 82 SpragueDawley rats (200-250 g) were randomly divided into five groups: sham group (n=18), ischemia/reperfusion group (n=18), EPO group (3 000 U/kg, 4 ml/kg, n=18), HBSP group (60 μg/kg, 4 ml/kg, n=18) and HBSP+LY294002 group(n=10). EPO or HBSP was injected from tail veins 5 min before reperfusion. The hemodynamic values were measured via a cannula inserted into the right common carotid artery, and cardiac functions were evaluated by echocardiograph 24 hours and 1 week after reperfusion. The infarct size was measured by TTC staining and the area at risk was assessed by evans blue staining. The expressions of Akt, phosphoAkt were detected by Western blotting and apoptosis of cardiomyocytes was detected by TUNEL. RESULTS: Compared with those in I/R group, the hemodynamic values of LVSP and±dp/dtmax and the cardiac functions improved after 24 hours and 1 week in EPO group and HBSP group. The infarct size also reduced and cardiomyocytes apoptosis was inhibited. The cardiomyocytes apoptosis was partially inhibited after blocked the levels of PI3KAkt in HBSP+LY294002 group (P<005). The expressions of phosphoAkt were upregulated by HBSP and the apoptotic index of cardiomyocytes in HBSP+LY294002 group was higher than that in HBSP group (P<005). The hemodynamic values and the cardiac functions after 24 hours and 1 week in the other groups were lower compared with those in sham operation group, and the infarct size and the apoptotic index of cardiomyocytes were higher than those in sham group (P<005). No statistically significant differences were found between EPO group and HBSP group. CONCLUSION: Helix B surface peptide could markedly improve heart functions and decrease the infarct size and myocardial apoptosis induced by ischemia/reperfusion injury in vivo rats, and its protective effects may possibly be though the activation of PI3KAkt signal pathway.

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备注/Memo

备注/Memo:
收稿日期：2012-11-07.
通讯作者：郭文怡，教授，主要从事冠心病介入与临床研究Email:guowenyi@tom.com
作者简介：蒋娜，硕士生Email:jnmiss.you@163.com
更新日期/Last Update: 2013-07-16