机械-电反馈引起心衰心室肌电重构变化的分子机制探讨

Molecular Mechanism of the Changes in Ventricular Electrical Remodeling Caused by Mechano-Electrical Feedback in Rabbits with Congestive Heart Failure

本研究试图探讨心衰时机械-电反馈引起的心室肌电重构的变化与L-型Ca2+通道和肌浆网Ca2+-ATP酶mRNA表达的关系。138只兔随机分为阿霉素组和正常组,在兔的心外膜分别以220/240/260次/min为刺激频率(基础周长273/250/231 ms)测定各部位的单向动作电位时程(MAPD)及心室有效不应期(VERP)。然后将刺激电极置于右房,以260次/min频率进行快速刺激,持续30 min。刺激结束后,再重复上述测定过程。并以S1S2S3刺激方法诱发心室颤动(VF),记录诱发率和VF持续时间,心室后除极的发生次数。然后,从这些心肌抽提总RNA,通过RT-PCR方法测定L-型Ca2+通道和肌浆网Ca2+-ATP酶的mRNA表达。在心衰组,增加前或后负荷快速刺激后L-型Ca2+通道的mRNA表达是上调的(P<0.05),肌浆网Ca2+-ATP酶的mRNA表达没有明显变化(P≥0.05),L-型Ca2+通道mRNA表达变化的幅度与MAPD90和VERP变化的幅度之间有相关性,肌浆网Ca2+-ATP酶的mRNA表达变化的幅度与MAPD90和VERP变化的幅度之间没有明显的相关性。本研究提示心衰时机械-电反馈对心室肌电重构的影响可能与L-型Ca2+通道mRNA的表达上调有关,而与肌浆网Ca2+-ATP酶的mRNA表达没有明显的相关性。

This study sought to explore the relationship between the change in ventricular electrical remodeling caused by mechano-electrical feedback and the expression of L-type Ca2＋-channel and/or sarcoplasmic reticulum Ca2＋-ATPase in the rabbits with congestive heart failure （CHF）. 138 rabbits were divided into two groups （CHF and control）. We measured the ventricular monophasic action potential duration （MAPD） and ventrieular effective refractory period （VERP） during ventricular pacing at the stimulus frequency of 220/240/260 bpm in these rabbits. Rapid atrial pacing （260/min） was given for 30 minutes. The MAPD and VERP were measured again. Then ventric- ular fibrillation was induced by S1S2 S3 program stimulation. We extracted the total RNA from the myocardium re- spectively and detected L-type Ca2＋-channel mRNA and sarcoplasmic retieulum Ca2＋-ATPase mRNA by use of Reverse Transcriptase-Polymerase Chain Reaction （RT-PCR）. In group CHF, with the increasing of preload/afterload, L-type Ca2＋-channel mRNA was up regulated after rapid atrial pacing when compared with that in control groups （P〈0. 05）. There was no significant change in sarcoplasmic reticulum Ca2＋-ATPase mRNA after rapid atrial pacing when compared with controls （P≥0.05）. The changes in MAPDg0 and VERP were related with the extent of L-type Ca2＋-channel mRNA up regulation. But the changes in MAPD00 and VERP were not significantly related with the extent of sarcoplasmic reticulum Ca2＋-ATPase mRNA up regulation. These findings suggest that Mechano-Electrical Feedback could increase the regional changes of ventricular electrical remodeling in rabbits with CHF and so to pre- dispose them to ventricular arrhythmia. The changes may be related with the up regulation of L-type Ca2＋-channel mRNA, but not with sarcoplasmic retieulum Ca2＋-ATPase mRNA.