[1]戴翠莲,姜黔峰,张新民.蛋白酶体抑制剂对心肌缺血再灌注大鼠CHIP、HSP70的影响[J].陆军军医大学学报(原第三军医大学学报),2010,32(06):550-553.
　Dai Cuilian,Jiang Qianfeng,Zhang Xinmin.Proteasome inhibitor improves expressions of CHIP and HSP70 in ischemia reperfusion rats[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(06):550-553.
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蛋白酶体抑制剂对心肌缺血再灌注大鼠CHIP、HSP70的影响(/HTML )
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陆军军医大学学报（原第三军医大学学报）[ISSN:1000-5404/CN:51-1095/R]

卷:
32卷
期数:
2010年第06期
页码:
550-553
栏目:
论著
出版日期:
2010-03-30

文章信息/Info

Title:
Proteasome inhibitor improves expressions of CHIP and HSP70 in ischemia reperfusion rats
作者:
戴翠莲; 姜黔峰; 张新民
遵义医学院附属医院心血管内科
Author(s):
Dai Cuilian;  Jiang Qianfeng;  Zhang Xinmin
Department of Cardiology, Affiliated Hospital, Zunyi Medical College, Zunyi, Guizhou Province, 563000, China
关键词:
蛋白酶体抑制剂; 热休克蛋白70羧基端相互作用蛋白; 热休克蛋白70; 心肌保护
Keywords:
proteasome inhibitor;  carboxyl terminus of the HSP70-interacting protein ;  heat shock protein 70 ;  myocardial protection
分类号:
R541.05;R977.3;R394.3
文献标志码:
A
摘要:
目的   观察蛋白酶体抑制剂MG-132(N-benz0y1oxycarbonyl(Z)-Leu -Leuleucina1)对急性缺血再灌注大鼠心肌(carboxyl terminus of the Hsc70-interacting protein, CHIP)、HSP70的影响以探讨MG-132的心肌保护机制。   方法   选择SD大鼠结扎左冠状动脉前降支30 min制作心肌缺血再灌注模型，54只大鼠按随机数字表法分入以下各组：治疗（I/R+T）组于再灌注前5 min静脉注射MG-132（0.75 mg/kg），对照（I/R）组及假手术（Sham）组注射生理盐水，并将I/R组和I/R+T组分为再灌注2、24 h及7 d亚组（各亚组各8只大鼠），分别用荧光定量PCR法及Western blot法检测CHIP及HSP70的mRNA及蛋白质表达，并进行相关性分析。   结果   与I/R各时相组相比，I/R+T各时相组CHIP及HSP70的mRNA水平显著升高[（0.87±0.10） vs （0.50±0.06）,（0.57±0.07） vs （0.33±0.04）,（0.47±0.06）vs （0.19±0.03）, P<0.01]。与I/R 2、24 h组相比I/R+T组CHIP及mRNA水平显著升高[（1.15±0.12）vs （0.57±0.07）,（0.81±0.09） vs （0.44±0.06）, P<0.01];MG-132上调了I/R+T各时相组HSP70的蛋白质表达，与I/R各组相比，差异均有统计学意义[（1.28±0.16）vs （0.79±0.08）, （0.88±0.12） vs （0.58±0.12）, （0.9±0.17） vs （0.50±0.09）, P<0.01]；MG-132上调了I/R+T 2、24 h组CHIP的蛋白质表达，与I/R 2、24 h组相比，差异有统计学意义[（1.43±0.15) vs (1.04±0.11), P<0.01；(1.16±0.11) vs (0.96±0.13)], P<0.05）。   结论   心肌缺血再灌注前适量静注MG-132能显著刺激缺血再灌注大鼠心脏CHIP表达，从而进一步上调HSP70水平，从而保护心肌。
Abstract:
Objective   To explore the influence of proteasome inhibitor, MG-132 (N-benz0y1oxycarbonyl(Z)-Leu-Leuleucina1) on the expressions of carboxyl terminus of the Hsc70-interacting protein (CHIP) and heat shock protein 70 (HSP70) in ischemia reperfusion (I/R) rats and investigate the underlying mechanism of myocardial protection by the inhibitor.    Methods   Totally 54 adult SD rats were randomly divided into 3 groups, sham group (n=6), I/R group (n=24) and treatment group (I/R+T, n=24). The later 2 groups were further equally divided into 3 subgroups according different time of reperfusion. Left anterior descending (LAD) coronary artery was ligated for 30 min and then released for 2 h or 24 h or 7 d in different subgroups. Five minutes before reperfusion, MG-132 at dose of 0.75 mg/kg was given intravenously in I/R+T group，but I/R group and sham group were given the same volume of normal saline. The levels of CHIP and HSP70 at mRNA and protein level were detected by real-time PCR and Western blotting respectively. The correlation between CHIP and HSP70 expression was analyzed.    Results   Compared with I/R groups, the mRNA levels of  CHIP and HSP70 were significantly increased in I/R+T groups (P<0.01). Accordingly, the protein expression of them in I/R+T groups were also notably raised compared with I/R groups (P<0.01). MG-132 exerted its strongest effect on upregulating the levels of CHIP and HSP70 in mRNA and protein in reperfusion for 2 h. Furthermore, the mRNA and protein levels of HSP70 had significant positive correlation with the expression of CHIP in all groups (r=0.94, P<0.01; r=0.89, P<0.05).    Conclusion   MG-132 may play a role in myocardial protection by upregulating the expression of CHIP in ischemia reperfusion rats, which then further increases the level of HSP70.

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[4]戴翠莲,罗开良.蛋白酶体抑制剂MG-132下调炎症因子表达抑制大鼠心肌再灌注损伤[J].陆军军医大学学报(原第三军医大学学报),2007,29(02):129.
　DAI Cui-lian,LUO Kai-liang.Proteasome inhibitor MG-132 inhibits myocardial reperfusion injury in rats by suppressing expression of inflammatory factors[J].J Amry Med Univ (J Third Mil Med Univ),2007,29(06):129.

更新日期/Last Update: 2010-03-24