卡维地洛对心肌梗死后心衰大鼠心肌肌浆网Ca^(2+)泵活性和Ca^(2+)释放通道密度的影响  

Carvedilol improves Ca^(2+) pump activity and Ca^(2+) release channels density in myocardial sarcoplasmic reticulum of rats with chronic heart failure caused by myocardial infarction

作　　者：耿召华[1] 刘春燕[1] 李隆贵[1] 赵晓辉[1] 崔斌[1] 于世勇[1] 

机构地区：[1]第三军医大学新桥医院心血管内科,全军心血管病研究所,重庆400037

出　　处：《第三军医大学学报》2009年第6期522-525,共4页Journal of Third Military Medical University

基　　金：重庆市自然科学基金(2006BB5380)~~

摘　　要：目的探讨β受体阻滞剂卡维地洛干预慢性心衰对心肌肌浆网(sarcoplasmic reticulum,SR)Ca2+泵活性和Ca2+释放通道(Type 2 Ryanodine receptor,RyR2)密度的影响及意义。方法通过结扎大鼠左冠脉建立慢性心衰模型,以大剂量卡维地洛(60mg·kg-1·d-1)进行干预,对照观察血流动力学、左室心肌SRCa2+泵活性、[3H]-ryanodine与RyR2最大结合量(Bmax)及Kd值。结果与假手术组(SH组)相比,心衰组(HF组)左室舒张末压(LVEDP)显著升高(P<0.01),左室压力上升、下降最大速度(+dp/dtmax、-dp/dtmax)显著降低(P<0.01),卡维地洛(Carv组)LVEDP显著低于心衰组(P<0.01),+dp/dtmax、-dp/dtmax显著高于心衰组(P<0.01);心衰组心肌SRCa2+泵活性、[3H]-ryanodine与RyR2最大结合量Bmax显著低于假手术组(P<0.01),卡维地洛组显著高于心衰组(P<0.01),3组Kd值差异不显著(P>0.05)。结论大剂量卡维地洛长期干预心梗后慢性心衰,能够改善心肌SRCa2+泵活性,增加RyR2密度,并改善心肌舒缩功能。Objective To study the effects of β-blocker carvedilol on the activity of Ca^2＋ pump and density of Ca^2 ＋ release channel type 2 ryanodine receptor （ RyR2 ） prevention and treatment of chronic heart failure. Methods of myocardial sarcoplasmic reticulum （SR） for the After the rat model of chronic heart failure was established by ligating the left coronary artery, the animals were divided into heart failure group （HF group, n = 17） and carvedilol treated group （Carv group, n = 18） which receiving intragastric injection of 60 mg · kg^-1 · d^-1 carvedilol 1 week after operation for 10 weeks. Another 18 rats were employed as control with sham operation （SH group）. The rats of HF group and SH group were given intragastric injection of 2 mL/d normal saline for the same time period with Carv group. Hemodynamic parameters, activity of SR Ca^2 ＋ pump, Bmax and Kd of [ ^3H ]-ryanodine binding to RyR2 were determined. Results Compared with SH group, left ventricular end-diastolic pressure （LVEDP） in HF group was increased （P 〈0. 01 ）, while their ＋ dp/dt and - dp/dtmax were decreased significantly （ P 〈 0. 01 ）. The LVEDP was lower but ＋ dp/dtmax and - dp/dtmax were significantly higher in Carv group than in HF group （P 〈 0.01 ）. The activity of SR Ca^2 ＋ pump and Bmax in HF group were lower than those in SH group （ P 〈 0.01 ）, and those in Carv group were higher than those in HF group （ P 〈 0.01 ）. There was no significant difference in Kd among the 3 groups （P 〉 0. 05）. Conclusion Long-term carvedilol administration for chronic heart failure caused by myocardial infarction improves the activity of Ca^2 ＋pump and increases the density of RyR2 of myocardial SR, and may be associated with the amelioration of the myocardial function and myocardial protection.

关 键 词：卡维地洛 心力衰竭 Ca^2+泵 Ca^2+释放通道 

分 类 号：R361.3[医药卫生—病理学] R541.605[医药卫生—基础医学]