高糖条件下致钙信号改变的机制研究

Mechanism of calcium signal change under condition of high glucose

摘要:

目的 探讨高糖对大鼠心房肌钙信号的影响及其机制。方法 分离大鼠心房肌细胞，分成2 部分： 第1 部分分左旋葡萄糖（LG）组、正常葡萄糖（NG）组、高葡萄糖（HG）组、HG+ 尿酸组；第2 部分分 过氧化亚硝基阴离子（ONOO-）组、分解后ONOO-（DC-ONOO-）组、ONOO-+ 尿酸组。观察钙瞬变、 钙通道蛋白RYR2、钙调控蛋白FKBP12.6 的变化。结果 HG 组的钙瞬变幅度较NG 组高，ONOO- 增加钙 释放，尿酸可以减弱其效应；HG 组和ONOO- 组RYR2 蛋白的表达降低，尿酸可抑制HG 和ONOO- 导致 的RYR2 蛋白表达效应，高糖可调控RYR2 蛋白上游调控分子FKBP12.6 的表达。结论 ①高糖及ONOO- 增加钙释放，氧化应激抑制因子―尿酸减少钙释放；②高糖减少RYR2 表达，尿酸可以抑制其效应；③高糖 可以通过氧化应激调控RYR2 上游信号通路分子FKBP12.6，从而调控钙信号。

Abstract:

Objective To investigate the effect of high glucose on calcium signals of atrial myocytes and its mechanism. Methods The experiment based on isolated atrial myocytes of rats were divided into two parts. The first section included L-glucose (LG), normal glucose (NG), high glucose (HG) and HG+uric acid groups. The second section included ONOO-, DC-ONOO-, and ONOO-+uric acid groups. The changes of calcium transient, calcium channel protein RYR2 and its regulatory protein FKBP12.6 were observed. Results Ca2+ transient amplitude was larger in the HG group compared with the NG group. Application of uric acid significantly decreased the Ca2+ transient amplitude whereas exposure of myocytes to ONOO- markedly increased it. The expression of RYR2 in the HG and ONOO- groups was decreased, uric acid inhibited the effect of HG and ONOO- on RYR2 expression. High glucose regulated the expression of FKBP12.6 in the upstream of RYR2 protein. Conclusions High glucose and ONOO- increase the release of Ca2+, application of uric acid significantly decreases the amplitude of Ca2+ transient. Incubation in high glucose decreases the expression of RYR2 protein, whereas uric acid increases the amount of RYR2 in atrial myocytes. High glucose-induced oxidative stress can regulate the upstream signaling pathways of RYR2 named FKBP12.6.