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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 investigate the effects of ubiquitin-proteasome system (UPS) on heat shock protein 27 (Hsp27) and its relationship with tumor necrosis factor-α (TNF-α) To investigate the possible mechanism of myocardial protection after UPS inhibition, and to provide a new way to reduce myocardial ischemia-reperfusion injury. Methods 64 SD rats were ligated with the left anterior descending coronary artery for 30 minutes to make the myocardial ischemia-reperfusion model. Ischemia / reperfusion (I / R) group, ischemia group (I) and ischemia reperfusion group (I / R + The sham group was injected with the same volume of saline. The extent of myocardial infarction and the expression of Hsp27 and TNF-α in each group were observed 6h after reperfusion. Results Compared with I / R group, the infarct size of I / R + T group was significantly decreased (P <0.05) and the expression of Hsp27 was significantly increased [95.37 ± 18.38 and 68.14 ± 17.58, P <0.01; protein integral optical density values were (82.57 ± 6.39) and (39.96 ± 7.28), respectively, P <0.001]. (45.53 ± 10.65) and (76.52 ± 19.12), respectively (P <0.01), and the protein integral optical density values were (60.12 ± 9.32) and (42.33 ± 5.95) P <0.01, respectively. Conclusion Appropriate inhibition of UPS can significantly increase the level of Hsp27, inhibit the expression of TNF-α, reduce the scope of myocardial infarction, with myocardial protection.