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目的观察蛋白酶体抑制剂MG-132(N-benz0y1 oxycarbonyl(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30min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5min静脉注射MG-132(0.75mg/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、24h及7d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/R2、24h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+T2、24h组CHIP的蛋白质表达,与I/R2、24h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。
Objective To investigate the effect of proteasome inhibitor MG-132 on the expression of CHIP and HSP70 in rats with acute ischemia-reperfusion injury. -132 myocardial protection mechanism. Methods Myocardial ischemia-reperfusion model was established by ligation of the anterior descending branch of left anterior descending coronary artery in SD rats. Fifty-four rats were randomly divided into the following groups according to random number table: treatment (I / R + T) The rats in control group (I / R) and Sham group were injected with MG-132 (0.75mg / kg) intravenously and I / R group and I / R + And 7d subgroup (8 rats in each subgroup). The mRNA and protein expression of CHIP and HSP70 were detected by fluorescence quantitative PCR and Western blot respectively, and the correlation was analyzed. Results The mRNA levels of CHIP and HSP70 in I / R + T groups were significantly increased compared with those in I / R groups [(0.87 ± 0.10) vs (0.50 ± 0.06 vs (0.57 ± 0.07 vs 0.33 ± 0.04), (0.47 ± 0.06) vs (0.19 ± 0.03), P <0.01]. The levels of CHIP and mRNA in I / R + T group were significantly higher than those in I / R2,24h group [(1.15 ± 0.12) vs (0.57 ± 0.07), (0.81 ± 0.09) vs (0.44 ± 0.06), P <0.01 ]; MG-132 up-regulated protein expression of HSP70 in each phase of I / R + T group compared with I / R group [(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 upregulated protein expression of CHIP in I / R + (1.43 ± 0.15) vs (1.04 ± 0.11), P <0.01; (1.16 ± 0.11) vs (0.96 ± 0.13)], P <0.05). Conclusion MG-132 pretreatment can significantly stimulate the expression of CHIP in the heart of rats with ischemia-reperfusion, and further up-regulate the HSP70 level to protect myocardium.