连接蛋白40／43调节大鼠血管平滑肌细胞内钙离子浓度与肠系膜上动脉收缩反应性的研究

Relationship between Cx40/43 regulating the intracellular Ca^2＋ concentration of vascular smooth muscle cell（VSMC） and endothelium-dependent vascular contractive response of superior mesenteric artery in rats

目的了解连接蛋白40（Cx40）／43调节失血性休克大鼠肠系膜上动脉（SMA）内膜依赖的血管收缩反应性，探讨与血管平滑肌细胞（VSMC）胞内钙离子浓度（[Ca^2＋]i）的关系。方法以传至3～5代培养的SD大鼠血管内皮细胞（VEC）及VSMC为研究对象，观察不同程度缺氧对SMA和VSMC收缩反应性的影响；用Cx40／43的反义寡脱氧核苷酸（ASODN）阻断SMA、VEC和VSMC的Cx40／43表达，观察Cx40／43对缺氧SMA的收缩反应性和VSMC[Ca^2＋]i的作用。结果缺氧后SMA和VSMC的收缩反应性均呈先增加后降低的变化过程；缺氧可以引起VSMC钙超载，[Ca^2＋]i从常氧状态下的（82±4）％增至缺氧30min时的（115±8）％和缺氧2h的（133±13）％；Cx40 ASODN可以增加VSMC的[Ca^2＋]i和SMA对杨梅黄酮的收缩反应性，Cx43 ASODN则引起相反效应。结论Cx40／43通过调节VSMC[Ca^2＋]i，间接参与调节休克后SMA内膜依赖的血管收缩反应性。

Objective To investigate the relationship between intracellular Ca^2＋ concentration （[Ca^2＋]i） mediated by eonnexin 40/43 （Cx40/43） of VSMC and endothelium-dependent vascular contrac- tive response of superior mesenteric arteries （SMA） in hemorrhagic shock rats. Methods Third to fifth passage culture of vascular endothelial cells （VEC） and VSMC from SD rats were used as study subject, the changes in contractive response of SMA and VSMC against hypoxia were observed. The expression of Cx40/ 43 in SMA,VEC,VSMC were blocked by Cx40/43 ASODN, then the effect of Cx40/43 on contractive re- sponse of hypoxic SMA and [ Ca^2＋] i of VSMC were observed. Results The contractive responses of SMA and VSMC after hypoxia were first increased, then decreased. Hypoxia induced calcium overload in VSMC [（82±4）% in normal control group, （115±8）% in hypoxia group at 30 min, （133±13）% in hypoxia group at 2 h]. Cx40 ASODN increased [Ca^2＋]i in VSMC and contractive response of SMA towards myrice-tin,while that of Cx43 ASODN showed opposite tendency. Conclusions Cx40/43 can regulate the SMA endothelium-dependent vascular contractive response through [Ca^2＋]i of VSMC after hemorrhagic shock.