风湿性心脏病心肌细胞内钙离子转运蛋白基因转录的变化

Gene transcription of calcium transport proteins in cardiomyocytes of patients with rheumatic heart disease

目的：探讨风湿性心脏病（风心病）慢性心衰时心肌细胞内Ｃａ２＋转运功能改变的分子机制。方法：应用斑点杂交方法测定１２例风心病患者心肌细胞内４种主要Ｃａ２＋转运蛋白：Ｌ－型钙通道（ＤＨＰＲ）α１亚基、钠钙交换体（ＮＣＥ）、肌浆网钙泵（ＳＥＲＣＡ２）和肌浆网Ｃａ２＋释放通道－兰尼碱受体（ＲｙＲ２）的基因转录变化。结果：风心病患者ＤＨＰＲα１、ＳＥＲＣＡ２和ＲｙＲ２ｍＲ－ＮＡ水平，以鸡磷酸－３－甘油醛脱氢酶（ＧＡＰＤＨ）ｍＲＮＡ为内对照，分别较正常对照显著下降１２．５％，３１．６％和１３．０％，以β－肌球蛋白重链（ＭＨＣ）ｍＲＮＡ为内对照，则比正常对照分别显著下降８．９％、２２．０％和９．０％；而ＮＣＥｍＲＮＡ水平在两种内对照情况下分别显著升高５６．０％和４１．５％。结论：风心病慢性心衰时心肌细胞内Ｃａ２＋转运功能改变的机制很可能主要在转录水平。

Objective: To explore the molecular mechanism of abnormal intracellular calcium transport in cardiomyocytes of patients with rheumatic heart disease (RHD). Methods: The relative mRNA levels for 4 types of Ca2+ transport proteins, including sarcolemma Ca2+ channeldihydropyridine receptor (DHPR) α1 subunit, Na+/Ca2+ exchanger (NCE), sacroplasmic reticulum (SR) Ca2+ ATPase (SERCA2) and Ca2+ release channelryanodine receptor (RyR2), were determined by dot blot hybridization. Results: As compared with controls (n=6), the relative levels of mRNA for DHPR α1 subunit, SERCA2 and RyR2 were decreased significantly in the myocardium of patients with RHD (n=12) as normalized per glyceraldehyde3phosphate dehydrogenase (GAPDH) mRNA (-12.5%, -31.6% and -13%, respectively, P<0.05～0.01), or per myosin heavy chain (βMHC) mRNA (-9.8%, -22.0 % and -9.0%, respectively, P<0.05～0.01), but the relative level of mRNA for NCE was increased significantly by 56% and 41% as normalized per GAPDH mRNA and βMHC mRNA, respectively(P<0.01). Conclusion: Abnormal gene transcription of main Ca2+ transport proteins is likely to be the main mechanisms of abnormal intracellular Ca2+ handling in the cardiomyocytes of patients with RHD.