摘要
目的研究泛素-蛋白酶体系统(ubiquitin-proteasome system,UPS)对心肌缺血再灌注大鼠热休克蛋白27(heat shock protein,Hsp27)的影响及与肿瘤坏死因子-α(TNF-α)的关系,探讨抑制UPS后可能的心肌保护作用机制,为降低心肌缺血再灌注损伤提供新的干预途径。方法64只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。缺血再灌注+治疗(I/R+T)组于再灌注前5min静脉注射蛋白酶体抑制剂MG-1320.75mg/kg,缺血再灌注(I/R)组、缺血(I)组及假手术(Sham)组注射与之相同容积的生理盐水。观察各组心肌梗死范围、再灌注6h后各组大鼠心肌组织Hsp27及TNF-α的表达。结果与I/R组相比,I/R+T组大鼠心肌梗死范围明显减少(P<0.05),Hsp27表达显著增加[mRNA水平分别为(95.37±18.38)和(68.14±17.58),P<0.01;蛋白质积分光密度值分别为(82.57±6.39)和(39.96±7.28),P<0.001]。TNF-α表达降低[mRNA分别为(45.53±10.65)和(76.52±19.12),P<0.01;蛋白质积分光密度值分别为(60.12±9.32)和(42.33±5.95),P<0.01]。结论适当抑制UPS能够显著升高Hsp27的水平,抑制TNF-α表达,减少心肌梗死范围,具有心肌保护作用。
Objective To study the influence on heat shock protein 27 （Hsp27） and tumor necrosis factor α （TNF-α） by inhibiting ubiquitin proteasome system in cardiac ischemia-reperfusion （I/R） rats. Methods Left anterior descending （LAD） coronary artery was ligated for 30 rain and then released for 6 h in adult Spra- gue-Dawley rats. Five minutes before reperfusion, MG-132 （N-benzoyloxycarbonyl （Z）-Leu-Leuleucinal） at dose of 0.75 mg/kg was given by vein injection in I/R ＋ T group, but I/R group, I group and sham group were given the same volume of sterile saline. The changes of myocardial infarct size, cardiac protein and mRNA lev- els of Hsp27 and TNF-oL were measured. Results Compared with I/R group, the myocardial infarct size was significantly reduced （P 〈 0.05 ） , while the protein and mRNA levels of Hsp27 were significantly increased （P 〈 0.01 ） and those of TNF-α were significantly lessened （P 〈 0.0l ） in I/R ＋ T group. Conclusion Myocardial reperfusion injury can be inhibited by appropriate inhibition of UPS, during which the level of Hsp27 was increased and the expression of TNF-α was suppressed.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2008年第22期2115-2119,共5页
Journal of Third Military Medical University
