帕瑞昔布对大鼠心梗后心室重构的改善作用及对PI3K/Akt信号通路的影响  

Improvement effects of parecoxib on ventricular remodeling after acute myocardial infarction in rats and its influence in PI3K/Akt signaling pathway

作　　者：余娅[1] 王虹又 易宗平 陈萍[1] 

机构地区：[1]重庆医科大学附属第一医院麻醉科,重庆400016

出　　处：《中国药理学通报》2017年第6期863-868,共6页Chinese Pharmacological Bulletin

基　　金：卫生部国家临床重点专科建设项目[财社(2011)170号];重庆市卫生局医学科学重点项目(2012-018);重庆市卫生局医学科研计划项目(No 2012-1-018);重庆市医学重点学科[渝卫科教(2007)2号]

摘　　要：目的探讨不同剂量的帕瑞昔布对大鼠心梗后心室重构的改善作用及对PI3K/Akt信号通路的影响。方法 40只♂SD大鼠随机分为5组(n=8):假手术组(S组)、心室重构模型组(R组)、帕瑞昔布低剂量组(P1组)、中剂量组(P2组)、高剂量组(P3组)。R组、P1组、P2组、P3组大鼠采用开胸结扎心脏左冠状动脉前降支的方法制备急性心肌梗死模型。建模24 h后连续2周每天分别给予P1组、P2组、P3组大鼠腹腔注射4、8、12 mg·kg^(-1)的帕瑞昔布,余2组给予等量的生理盐水。于建模处置4周时右侧颈动脉插管的方法测定大鼠血流动力学变化;处死大鼠,取心脏测定左室肥厚指数;HE染色、Masson染色观察梗死周边区心肌组织病理变化及间质胶原纤维增生情况;TUNEL染色光镜下观察心肌细胞凋亡情况;RT-PCR法检测心肌梗死周边区ANP mRNA、BNP mRNA含量的变化;Western blot法测定心肌PI3K、Akt、p-Akt及caspase-3的蛋白表达。结果与S组比较,心室重构模型组血流动力学各项指标明显变化,左室肥厚指数、ANP mRNA、BNP mRNA及caspase-3的蛋白表达明显升高,PI3K、p-Akt的蛋白表达明显降低(P<0.05)。与R组比较,中、高剂量帕瑞昔布可改善大鼠血流动力学,降低左室肥厚指数(P<0.05)。低、中、高剂量帕瑞昔布组均可降低ANP mRNA、BNP mRNA及caspase-3的蛋白表达,提高PI3K、p-Akt的蛋白表达(P<0.05)。结论中、高剂量帕瑞昔布能延缓心肌梗死大鼠的左心室重构过程,改善心脏功能,这种保护作用可能与PI3K/Akt信号通路的激活有关。Aim To observe the improvement effects of parecoxib on ventricular remodeling after acute myocardial infarction in rats and its influence on PI3K/Akt signaling pathway. Methods Forty male SpragueDawley rats were randomly divided into five groups( n= 8) : sham operation group( group S),ventricular remodeling model group( group R),low dose of parecoxib group( group P1),middle dose of parecoxib group( group P2),and high dose of parecoxib group( group P3). A myocardial infarction model was established by ligating the left anterior descending branch( LAD) of coronary artery in group R,group P1,group P2 and group P3. One day after the operation,the rats were given intraperitoneal injection of 4,8,12 mg · kg^(-1) parecoxibin Group P1,group P2 and group P3,respectively,for two weeks. The same volume saline was given in group S and group R. Four weeks later,LVSP,LVEDP,+ dp/dt_(max),-dp/dt_(max) were monitored. The hearts were harvested to calculate left ventricular hypertrophy index. The pathological change of heart was examined with an optical microscope. The expressions of atrial natriuretic peptide( ANP) mRNA and brain natriuretic peptide( BNP) mRNA were detected by RTPCR. The expression of PI3 K,Akt,P-Akt and caspase-3 was detected by Western blot. Results Compared with group S,the cardiac function was decreased,the left ventricular hypertrophy index,the expression levels of ANP,BNP mRNA,caspase-3 were increased,and the expression levels of PI3 K,P-Akt were reduced in group R( all P < 0. 05). Compared with group R,the cardiac function was ameliorated,the left ventricular hypertrophy index were reduced in group P2 and group P3( all P < 0. 05). The expression levels of ANP,BNP mRNA,Caspase-3 were decreased,and the expression levels of PI3 K and P-Akt were increased in group P1,group P2 and group P3( all P < 0. 05). Conclusions Middle and high doses of parecoxib can mitigate the process of ventricular remodeling after myocardial infarctionand improve the myocardial function,and its underlying mechanism may be related to

关 键 词：心肌梗死 心室重构 环氧化酶2抑制剂 帕瑞昔布 凋亡 PI3K/AKT信号通路 

分 类 号：R-332[医药卫生] R322.11