FKBP12.6基因调控犬慢性充血性心力衰竭RyR2通道研究  

FKBP12.6 gene regulation of RyR2 channels in chronic congestive heart failure canines

作　　者：冯艳[1] 孙娟[2] 黄榕[1] 任澎[1] 

机构地区：[1]新疆维吾尔自治区人民医院心电学科,乌鲁木齐830001 [2]新疆医科大学博士后流动站,乌鲁木齐830054

出　　处：《中华实用诊断与治疗杂志》2014年第7期641-644,共4页Journal of Chinese Practical Diagnosis and Therapy

基　　金：新疆维吾尔自治区科技支疆项目(2013911119);新疆维吾尔自治区自然科学基金(2012211A091)

摘　　要：目的探讨心肌肌浆网FKBP12.6钙调蛋白调控犬慢性充血性心力衰竭右心室肌雷尼丁受体2(ryanodine receptor 2,RyR2)通道功能的机制。方法杂种犬18只随机分为假手术组、心力衰竭+AAV9/EGFP组(EGFP组)与心力衰竭+AAV9/FKBP12.6-EGFP(FKBP12.6-EGFP组)各6只,EGFP组和FKBP12.6-EGFP组右心室植入起搏器快速起搏4周制备慢性充血性心力衰竭模型,分别含AAV9/EGFP和AAV9/FKBP12.6-EGFP的腺病毒相关溶液各500μL;假手术组右心室仅植入起搏器,经胸心包腔内注射生理盐水500μL。实验8周时3组行超声心动图检查心功能,采用心内电生理技术检测右心室单相动作电位复极90%时程(MAPD90),采用冰冻组织病理检查心室肌FKBP12.6荧光蛋白表达情况,采用免疫组织化学法检测RyR2蛋白表达情况。结果犬右心室快速起搏4周后,EGFP组和FKBP12.6-EGFP组平均动脉压<60mm Hg,左室射血分数<50%,心力衰竭模型成功建立;实验8周时,EGFP组平均动脉压((54.45±8.45)mm Hg)、左室射血分数((0.45±0.03)%)、MAPD90((65.20±5.30)ms)及右心室RyR2蛋白表达水平((15.65±2.65)个)均明显低于假手术组((138.75±6.56)mm Hg、(0.72±0.01)%、(110.50±6.55)ms、(28.85±2.55)个)和FKBP12.6-EGFP组((135.60±6.40)mm Hg、(0.75±0.03)%、(105.50±4.20)ms、(30.25±2.95)个)(P均<0.05),假手术组与FKBP12.6-EGFP组比较差异无统计学意义(P>0.05);假手术组犬心肌组织FKBP12.6蛋白表达呈阳性,EGFP组呈弱阳性,FKBP12.6-EGFP组呈强阳性。结论肌浆网FKBP12.6钙调蛋白可上调RyR2通道功能,改善犬心力衰竭的电不稳定特性。Objective To study the mechanism of myocardial sarcoplasmic reticulum FKBP12. 6 calmodulin regulating ryanodine receptor 2 （RyR2） in chronic congestive heart failure （CHF） in canines. Methods Eighteen canines were randomly divided into three groups： sham operation group, CHF model＋ adeno-associated virus 9/green fluorescent protein group （EGFP group） and CHF model＋AAVg/ FKBP12. 6-EGFP group （FKBP12. 6-EGFP group）, with 6 canines in each group. EGFP group and FKBP12. 6-EGFP group were implanted pacemaker in the right ventricle with rapid pacing for 4 weeks to establish CHF models, and were respectively injected AAV9/EGFP solution and AAV9/ FKBP12.6-EGFP solution into the pericardial cavity （500 μL for each canine）. Sham operation group was only implanted pacemaker in the right ventricle and was injected 500 μL normal saline. Echocardiography was done in these groups to detect heart function. Intracardiac electrophysiological technique was used to detect ventricular monophasic action potential duration at 90 % repolarization （MAPD90）. FKBP12.6 fluorescent protein expression was detected on the frozen sections of ventricular muscle. The expression of RyR2 protein was examined by immuno-histochemistry. Results After 4 weeks of right ventricular rapid pacing, the CHF canine models were successfully established in EGFP group and FKBP12.6-EGFP group, with mean arterial pressure （MAP） 〈 60 mm Hg and left ventricular ejection fraction （LVEF） 〈50%. After8 weeks, MAP, LVEF, MAPD90 and RyR2 were （54.45±8.45） mm Hg, （0.45±0.03）%, （65.20±5.30） ms and 15.65±2.65 in EGFP group, significantly lower than those in sham operation group （（138.75± 6.56） mm Hg, （0.72±0.01）%, （110.50±6.55） ms, 28.85±2.55） and FKBP12.6-EGFP group （（135.60±6.40） mm Hg,（0.75±0.03）%, （105. 50±4. 20） ms, 30. 25 ± 2. 95） （P〈0.05）. There were no significant differences between sham operation group and FKBP12. 6-EGFP group （P〉0.05）. The expression of

关 键 词：心力衰竭 FKBP12.6钙调蛋白 雷尼丁受体2 犬 

分 类 号：R541.6[医药卫生—心血管疾病]