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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

24卷

期数:

2018年02期

页码:

116-121

栏目:

出版日期:

2018-03-20

文章信息/Info

Title:

Inhibiting effect of preconditioning by trimetazidine on apoptosis of cadiocyte and its mechanism in rats during ischemia-reperfusion injury

作者:

熊果; 马康华

四川省宜宾市第一人民医院心血管内科，宜宾 644000

Author(s):

XIONG Guo ;  MA Kang-hua

Department of Cardiology，The First People’s Hospital of Yibin City in Sichuan Province, Yibin 644000，China

关键词:

心肌; 缺血/再灌注损伤; 细胞凋亡; 曲美他嗪; 环磷酸腺苷反应蛋白结合元件; Bcl-2; Caspase-3; 大鼠

Keywords:

myocardium;  ischemia-reperfusion injury;  apoptosis;  trimetazidine;  CREB;  Bcl-2;  Caspase-3;  rat

分类号:

R54

DOI:

-

文献标志码:

A

摘要:

目的：探讨曲美他嗪预处理对缺血/再灌注大鼠心肌细胞凋亡的抑制作用及其可能机制。方法： 实验大鼠60只被随机分为假手术组（Sham）、缺血再灌注组（I/R)及预处理缺血再灌注组（T+I/R）各20只，除Sham组外各组缺血45 min，再灌注180 min建模，后用TUNEL法检测各组心肌细胞凋亡；免疫组化检测p-CREB蛋白表达，免疫荧光检测Bcl-2与Caspase3蛋白表达；RT-PCR法检测CREB、Bcl-2及Caspase-3基因表达，比较各组结果。结果： (1)I/R组细胞凋亡最多，T+I/R组细胞凋亡明显减少，但仍多于Sham组（P均<0.05)；(2) I/R组表达CREB最少、T+I/R组最高、Sham组居中（P均<0.05)；(3) Sham组p-CREB少量表达、I/R组增加、T+I/R组显著增加（P均＜0.05）；(4)Sham组Bcl-2高表达、I/R组低表达、而T+I/R组居中（P均＜0.05）；(5)I/R组Caspase-3表达显著上调、T+I/R组显著下调、Sham组最低（P均<0.05）。结论： 曲美他嗪预处理能显著抑制缺血/再灌注大鼠心肌细胞凋亡，其机制可能与其活化CREB，上调p-CREB及Bcl-2的表达，下调Caspase-3的表达有关。

Abstract:

Objective: To investigate the inhibiting effect and possible mechanism of preconditioning by trimetazidine (TMZ) on apoptosis of cadiocyte in rats during ischemia-reperfusion injury. Methods：A total of 60 SD rats were randomly divided into sham group, ischemia-reperfusion group (I/R group), preconditioning group by TMZ (T+I/R group) with 20 rats in each group. The models of ischemia-reperfusion injury were constructed after keeping ischemia for 45 min and followed by reperfusion for 180 min after feeding the rats for 14 days for each group. TUNEL stain was adopted to detect the apoptosis of myocardial cells of each group. Immunohistochemistry was used to check the expression of phosphated cAMP-response element binding (p-CREB) protein and immunofluorescence technique was used to analyze the levels of Bcl-2 and Caspase-3 proteins. Reverse transcription polymerase chain reaction (RT-PCR) was adopted to detect mRNA levels of Bcl-2, Caspase-3 and cAMP-response element binding (CREB). Results：（1）The apoptosis index (AI) of cardiocytes of I/R group was higher than that of the other two groups (P＜0.05）. The AI of cardiocytes of T+I/R group was higher than that of sham group (P＜0.05）. （2）The expression of CREB protein in I/R group was lower than that in sham group. The expression of CREB protein in T+I/R group was higher than that in sham group(P＜0.05）. （3）The expression of p-CREB protein in sham group was lower than that in I/R group，and the expression of p-CREB protein was significantly increased in T+I/R group compared with I/R group (P＜0.05）. （4）The expression of Bcl-2 protein was the highest in sham group，and lowest in I/R group. The expression of Bcl-2 in T+I/R group was significantly increased compared with I/R group but lower compared with sham group (all P＜0.05 ）.（5）Compared with I/R group, the expression of Caspase-3 was significantly decreased in T+I/R groups(P＜0.05）(but higher than that in Sham group). Conclusion：The preconditioning by TMZ has the inhibitory effect on apoptosis of cadiocyte in rats during ischemia-reperfusion process. And its possible mechanisms may be that CREB, p-CREB and Bcl-2, and Caspase-3 are activated, up-regulated and down-regulated by TMZ, respectively.

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相似文献/References:

[1]刘建华,蒋 伟,石 光,等.缺血预处理对心脏瓣膜术中脏器的保护作用[J].天津医科大学学报,2018,24(06):513.
　LIU Jian-hua,JIANG Wei,SHI Guang,et al.Protective effect of ischemic preconditioning on the viscera during cardiac valve surgery[J].Journal of Tianjin Medical University,2018,24(02):513.

备注/Memo

备注/Memo:

文章编号 １００６－８１４７（２０18）０2-0116-06
作者简介 熊果（1976-），男， 主治医师，硕士 ，研究方向：冠心病发病机制；通信作者：马康华，E-mail: markcq111@yahoo. com.cn。

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更新日期/Last Update: 2018-03-20