机械-电反馈引起心衰心室肌电重构变化的分子机制探讨

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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 was designed to investigate the relationship between changes in ventricular myoelectrical remodeling induced by mechanical-electrical feedback and the expression of Ca2 + -ATPase mRNA in L-type Ca2 + channels and sarcoplasmic reticulum in heart failure. 138 rabbits were randomly divided into doxorubicin group and normal group, the rabbit epicardial were 220/240/260 times / min for the stimulation frequency (basal circumference 273/250/231 ms) to determine the unidirectional Action potential duration (MAPD) ​​and ventricular effective refractory period (VERP). The stimulation electrodes were then placed in the right atrium and stimulated rapidly at 260 cycles / min for 30 min. After stimulation, repeat the above measurement procedure. Ventricular fibrillation (VF) was induced by S1S2S3 stimulation, and the induction rate and VF duration were recorded. The incidence of post-ventricular depolarization was recorded. Then, total RNA was extracted from these myocardium and the mRNA expression of L-type Ca2 + channel and sarcoplasmic reticulum Ca2 + -ATPase was determined by RT-PCR method. In heart failure group, the mRNA expression of L-type Ca2 + channel was up-regulated (P <0.05), and the mRNA expression of Ca2 + -ATPase in sarcoplasmic reticulum did not change significantly (P> 0.05) after L - Ca2 + channel mRNA expression amplitude and MAPD90 and VERP changes in the magnitude of the correlation between sarcoplasmic reticulum Ca2 + -ATPase mRNA expression amplitude and MAPD90 and VERP amplitude of the change was not significantly correlated. The present study suggests that the influence of mechanical-electrical feedback on ventricular myoelectrical remodeling may be related to the up-regulation of L-type Ca2 + channel mRNA expression but not to the sarcoplasmic reticulum Ca2 + -ATPase mRNA expression.
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