风湿性心脏病心肌细胞内肌浆网钙离子转运功能变化的机制

Mechanism of the Alteration in Cardiac Sacroplasmic Reticulum Ca^(2+) Transport in Patients of Rheumatic Heart Disease With Chronic Heart Failure

目的：探讨风湿性心脏病（风心病）慢性心力衰竭时心肌细胞内肌浆网Ca2+转运功能变化的机制。方法：采用Westernblot法测定19例风心病患者（风心病组）和6例意外脑死亡者（对照组）心肌肌浆网钙泵蛋白和兰尼碱受体含量，同时采用草酸盐易化的肌浆网Ca2+摄取法测定两组心肌肌浆网的Ca2+摄取功能，采用测定“裸露”心肌束的咖啡因敏感性方法测定风心病患者心肌肌浆网的Ca2+释放功能。结果：风心病组钙泵蛋白和兰尼碱受体相对含量比对照组分别显著减少23％（P＜0．01）和10％（P＜0．05），心肌匀浆肌浆网Ca2+摄取量和摄取率也均显著低于对照组（P＜0．05～P＜0．01），并且风心病患者钙泵蛋白相对含量变化与肌浆网Ca2+摄取率变化呈显著正相关（r=0．81，P＜0．01），“裸露”心肌束的相对Ca2+释放速率变化也明显低于正常水平，且与兰尼碱受体相对含量变化密切相关（r=0．67，P＜0．05）。结论：风心病心肌细胞内肌浆网Ca2+摄取和释放功能下降的机制主要与肌浆网的Ca2+摄取和释放蛋白含量变化有关。

Objective:To explore the mechanism of the alteration in cardiac sacroplasmic reticulum (SR) Ca2+ transport in patientsof rheumatic heart disease (RHD) with chronic heart failure.Methods:The relative levels of SR Ca2+-adenosine triphosphatase(SERCA2 ) and Ca2+ release channel-ryandine receptor(RyR2) were measured by western blot analysis in 19 patients with RHD (RHD group) and in 6 accidentally brain-deadpersons withbut cardiovascular diseases (control group). The SR Ca2+ uptake was measured by the method of oxalate-facilitated Ca2+ uptake in both groups and the SR Ca2+ release activity was monitored indirectly by the measurement of caffeinesensitivity of chemically skinned myocardial fibers of patients with RHD.Results: The relative levels of SERCA2 and RyR2 decreased significantly by 23 % (p＜0. 01 ) and 10 % (p＜0. 05 )in patients with RHD,respectively. The amount and the rates of SR Ca2+uptake in homogenates of cardiomyocytes were significantly lower in patients with RHD than that in controls,and the velocities of SR Ca2+ release (Vo/Vm) of skinned myocardial fibers in patients with RHD were markedly lower as compared with the normal levels. Moreover,linear correlation analysis showed that the alterations in relative levels of SERCA2 and RyR, were correlated closely with the changes of SR Ca2+uptake rates and Vo/Vm in patients with RHD,respectively (r=0. 81, p＜0. 01 ; r=0. 67, p＜0. 05; respectively).Conclusion: The mechanism of the alteration in cardiac SR Ca2+ transport in patients with RHD is related to thechanges of cardiac SR Ca2+ uptake and release transporting proteins.