肌浆网钙泵基因过表达对快速起搏右房引起的急性心功能不全及电生理的影响

Effection of SERCA2a gene overexpression on induced acute heart failure and electrophysiology in rapid right atrium pacing rabbit model

目的研究心肌肌浆网Ca2+-ATP酶(SERCA2a)基因过表达对快速起搏右房(RAP)兔心功能及电生理的影响。方法将新西兰大白兔动物模型随机分为假手术组(A组);腺相关病毒/绿色荧光蛋白(AAV1/EGFP)+心房颤动(简称房颤)模型组(B组);AAV1/SERCA2a+房颤模型组(C组);每组各12只。A、B、C组心包腔内分别注射生理盐水、含AAV1/EGFP液、含AAV1/SERCA2a液各500μl。4周后,行心脏超声检测心功能,并行短期RAP24 h,采用心内电生理技术检测各组心房有效不应期(AERP)。处死各组动物,行免疫组化检测SERCA2a在心肌中的表达情况。结果与A组比较,B组起搏8,12,24 h后AERP明显缩短(P<0.05),而C组无明显变化(P>0.05)。与A组比较,B组左室射血分数(LVEF)降低(P<0.05),C组未见明显变化(P>0.05),C组SERCA2a在心房心肌组织中呈强阳性表达。结论 SERCA2a在心房肌组织中过表达有抗快速起搏致AERP缩短作用,并有保护心功能的效益。

Objective To study on effect of sarcoplasmic reticulum Ca2 ＋ATPase （SERCA2a） gene overexpression on induced acute heart failure and electrophysiology in rapid right atrium pacing rabbit model. Methods Animals were di- vided into four groups： sham operation group （A group） ; adeno-associated virus/green fluorescent protein （AAV1/EGFP） ＋ atrial fibrillation （ AF ） model group （ group B） ; AAV1/SERCA2a ＋ AF model group （ group C） ; Each group of each 12（n = 12）. A, B, C group were respectively injected with saline, containing AAV1/EGFP solution, containing AAV1/ SERCA2a solution in the pericardial cavity （500μ1 for each animal）. After four weeks, cardiac function were determined by echocardiographic, and the effect on atrial effective refractory period （AERP） was evaluated by intracardiac electrophys- iological technique after short-term rapid pacing to right atrium in 24 h. After handling the experimental animals death, im- munohistochemical detection of the expression of SERCA2a in myocardium was performed. Results Compared with A group, AERP significantly decreased in B group （P 〈 0.05 ） after 8,12,24 h pacing, and C group showed no significant change （P 〉 0.05 ）. Compared with A group, left ventricular ejection fraction （LVEF） significantly decreased in B group （P 〈 0.05 ）, C group had no significant changes （ P 〉 0.05 ）. SERCA2a was strongly positive expression inleft and right atrial myocardial tissue in C group. Conclusion Overexpression of SERCA2a in atrial tissue of rapid pacing could cause AERP shorten and protect cardiac function.