超压力负荷诱导肥厚心肌的肌浆网钙摄取和释放的改变

Changes of Ca^(2+) pumps and Ca^(2+) release channels in hypertrophied myocardium mediated by overload pressure in rats

目的探讨超压力负荷下左心室心肌肌浆网钙ATP酶、雷诺定受体2(ryanodine receptor2,RYR2)和三磷酸肌醇受体1(inositol1,4,5-trisphosphate receptor1,IP3R1)变化以及血管紧张素Ⅱ受体阻断药的影响。方法用腹主动脉缩窄法建立大鼠超压力负荷模型。检测心肌肌浆网钙ATP酶活性、Ca2+最大摄取速率、Ca2+最大摄取量、3H-雷诺定与RYR2最大结合量和RYR2受体密度。用免疫印迹法检测心肌肌浆网钙ATP酶2a(SERCA2a)蛋白表达;用反转录-聚合酶链反应检测心肌RYR2和IP3R1的mRNA表达。结果高压力负荷下左心室心肌呈典型的肥厚心肌的形态改变。手术组左心室心肌内浆网钙ATP酶活性、Ca2+最大摄取速度、Ca2+摄取量、RYR2最大结合量、RYR2的mRNA表达[吸光度/磷酸甘油醛脱氢酶]、IP3R1mRNA表达[吸光度/磷酸甘油醛脱氢酶]均低于假手术组(差异有统计学意义,P<0.01,n=12),缬沙坦组高于手术组及PD123319组(P<0.05),手术组与PD123319组间差异无统计学意义(P>0.05,n=12)。结论超压力负荷诱导的肥厚心肌组织钙调节能力明显下降,但缬沙坦可改善肥厚心肌组织的钙调节能力。

Objectives To invesitgate the changes of Ca^2＋ pumps, Ca^2＋ release channels such as ryanodine receptor （RYR2） and inositol 1, 4, 5-trisphosphate receptor （IP3R1） in hyptertrophied myocardium mediated by overloaded pressure in rats, and effects of angiotension Ⅱ （Ang Ⅱ ） receptors （AT1, AT2） antagonists on them. Methods Overloaded pressure rat model was established by abdominal aorta constriction. Thirty male Wistar rats were divided randomly into four groups, namely sham-operated group, banding group, valsartan group （banding group and valsartan administration）, and PD123319 group （banding group and PD123319 administration）. Activity of SR Ca^2＋ pumps, Bmax of ^3H-ryanodine （RY） binding to RYR2 were determined, western blot was used to assay the protein expression of sarcoplasmic reticulum Ca^2＋ ATPase （SERCA2a）, mRNA expressions of RYR2 and IP3R1 in myocardial tissues were analyzed by reverse transcriptase-polymerase chain reaction （RT-PCR）. Results Pathological changes of left myocardial tissues under overload pressure showed typical myocardial hypertrophy in rats. Activity of SR Ca^2＋ pumps, Bmax of ^3H-ryanodine （RY） binding to RYR2, protein expression of sarcoplasmic reticulum Ca^2＋ ATPase （SERCA2a）, mRNA expressions of RYR2 and IP3R1 of left ventricular myocardium tissues in banding group were lower than those in of sham-operated group, valsartan group and PD123319 group （P〈0.01）, in valsartan group they were higher than those in banding and PD123319 groups （P〈0.05） , but there were no big differences between banding and PD123319 groups （P〉0.05）. Conclusions Capability of calcium regulation of hypertrophied myocardium mediated by overloaded pressure rat model may be decreased, but AT1 receptor antagonists can improve the capability of calcium regulation of hypertrophied myocardium.