缺血预适应影响缺血心肌钙稳态的分子学机制

Molecular Mechanism Underlying Effects of Ischemic Preconditioning on Calcium Homeostasis in Ischemic Myocardium

目的:从调控钙稳态,了解α1受体在大鼠缺血心肌中发挥效应的机制。方法:Langendorff灌流模拟心肌缺血。实验组分为缺血前用苯肾上腺素(phehylephine)亚组(称为A组)和缺血前用哌唑嗪(prazosin)亚组(称B组),使用免疫组化与生化技术观察Bcl-2、胞浆钙、线粒体钙的变化。结果:A组[Ca2+]c(胞浆钙浓度)为(5.7±1.5)nmol/mg pro.(毫克蛋白)、[Ca2+]m(线粒体钙浓度)为(8.2±2.2)nmol/mg pro.,B组的[Ca2+]c为(9.2±1.4)nmol/mg pro.、[Ca2+]m为(22±2.6)nmol/mg pro.,A组的[Ca2+]c和[Ca2+]m均较B组明显降低(P<0.01)。缺血前激活α1受体,缺血时Bcl-2表达(50.9±9)‰。结论:α1受体通过影响Bcl-2表达,改变胞膜、内质网线粒体Ca2+活性,参与调控心肌细胞的钙稳态。

Objective： To understand the role of α1-adrenoceptors in ischemic myocardium by modulation of calcium homeostasis. Methods： Ischemia model was obtained according to Langendorff＇s method. The experimental group were divided into phenylephrine preconditioned group （ Graup A） and prazosin preconditioned group （ Group B）. Changes in Bcl-2, [ Ca^2＋] c, [ Ca^2＋ ] m were measured using immunohistology and biochemical techniques. Results： During ischemia, lower levels of [ Ca^2＋ ] c [ （ 5.7 ± 1.5 ） vs （ 8.2 ± 2.2 ） nmol/mg pro. ] and [ Ca^2＋ ] m [ （ 9.2 ± 1.4 ） vs （22 ±2.6 ） nmol/mg pro. ] were shown in the phenylephrine preconditioned group as compared with the prazosin preconditioned group. Pre-ischemic activation of α1-adrenoceptors also increased the expression of Bcl-2 to （50.9 ± 9） ‰. Conclusion： α1-adrenoceptors appear to play a role in calcium homeostasis in ischemic myocardium by effects on Bcl-2 expression, which in turn changes the activity of calcium channel on cellular membrance, endoplasmic reticulum and mitochondria.