摘要
目的:观察蛋白酶体抑制剂MG-132对急性缺血/再灌注大鼠心肌结构及功能的影响。方法:44只SD大鼠随机分为假手术(Sham)组12只、缺血再灌注(I/R)组16只及缺血再灌注治疗(I/R+T)组16只;根据再灌注时间不同,各组大鼠又被分为24h及7 d亚组。结扎左冠状动脉前降支30 min制作心肌缺血再灌注模型I,/R+T组于再灌注前5 min静脉注射MG-132(0.75mg/kg)I,/R组及Sham组注射生理盐水,观察各组恶性心律失常的发生率、血流动力学参数、心肌组织结构改变及脑钠肽水平。结果:与I/R组相比I,/R+T组室性心动过速发生率明显降低(34%vs 67%,P<0.05),心律失常起始时间比IR组显著延迟[(102.0±11.0)s vs(406.0±36.7)s,P<0.01];心功能检测显示,7 d后左心室收缩压(Left ventricular systolic pressure,LVSP)及左心室等容收缩期内压最大上升速率(The maximumrate ofleft ventricular pressure rise,+dp/dtmax)增加显著[,分别为(126.45±13.41)mmHg vs(108.64±15.61)mmHg,P<0.05;5 355±754 mmHg/s vs 4 860±680 mmHg/s,P<0.05],左心室舒张未压(Left ventricular end-diastolicpressure,LVEDP)明显降低[(15.50±6.94)mmHg/s vs(20.66±8.80)mmHg/s,P<0.05],脑钠肽水平由I/R组的(1 486±142)pg/ml降低至(231±134)pg/ml(P<0.01)。病理形态学发现,MG-132能显著减少心肌缺血再灌注后心肌细胞坏死、炎症细胞浸润和纤维结缔组织增生,改善心肌组织重塑。结论:蛋白酶体抑制剂能够改善缺血再灌注后的心肌结构和功能,具有心脏保护作用。
Objective：To investigate the influence of proteasome inhibitor MG-132 prior to reperfusion in rat acute myocardial ischemia-reperfusion model whether MG-132 could improve myocardial structure and its function. Methods：44 Adult Sprague-Dawley rats were randomly divided into 3 groups：left anterior descending（LAD）coronary artery ligation for 30 minutes with subsequent 24 hours and 7 days reperfusion （I/R groups）,LAD ligation for 30 minutes with subsequent 24 hours and 7 days reperfusion with treatment by MG-132（I/R＋T groups）,and Sham group. After LAD was ligated for 25 min,5 min before reperfusion,MG-132（0.75 mg/kg）was given by vein injection in I/R＋T groups,and other groups were given by the same capacity of sterile saline. The incidence of malignant arrhythmia,hemodynamic parameters,the structure of myocardial tissue and the level of B-type natriuretic peptide were measured. Results：Compared with I/R group,the incidence of malignant arrhythmia was decreased （34% vs 67% ,P 0.05）,the initiate of ventricular arrhythmia was delayed （102.0±11.0）s vs （406.0±36.7）s,P0.01,the left ventricular systolic pressure （LVSP）and ＋dp/dtmax were significantly raised in I/R＋T group （126.45±13.41）mmHg vs （108.64±15.61）mmHg,P0.05;（5 355±754） mmHg/s vs （ 4 860±680 ） mmHg/s , P0.05 , respectively ） . In the same time , we also found that B-type natriuretic peptide were decreased in I/R＋T group than in I/R group（231±134）pg/ml vs（1 486±142）pg/ml,P0.01 and MG-132 can improve the myocardial structure injury and inhibit the ventricular remodeling as well. Conclusion ： Our results demonstrate that MG-132 could improve the myocardial structure and function , and play a very important role in myocardial protection.
出处
《重庆医科大学学报》
CAS
CSCD
北大核心
2010年第10期1486-1489,共4页
Journal of Chongqing Medical University
基金
贵州省教育厅青年基金(编号:C-358)
贵州省优秀科技教育人才省长专项资金(编号:黔省专合字[2007]81号)
贵州省科技厅基金(编号:黔科合字[2007]2222号
关键词
蛋白酶体抑制剂
心功能
脑钠肽
心脏结构
Proteasomeinhibitor
Heartfunction
B-typenatriuretic peptide
Cardiac structure
