H_2S对大鼠大脑中动脉平滑肌细胞膜电位的超极化作用  

Hyperpolarization of hydrogen sulfide on the membrane potential of vascular smooth muscle cell in rat middle cerebral artery

作　　者：蔡圣年[1] 范一菲[1] 陈志武[1] 

机构地区：[1]安徽医科大学药理学教研室

出　　处：《中国临床药理学与治疗学》2011年第2期155-159,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：高等学校博士学科点专项科研基金(2005Z031);国家自然科学基金(30840104)

摘　　要：目的：探讨大鼠大脑中动脉（middle cerebral artery,MCA）内皮源性超极化因子（endo-thelium-derived hyperpolarizing factor,EDHF）介导的平滑肌细胞（VSMC）静息膜电位超极化作用与硫化氢（hydrogen sulfide,H2S）的关系。方法：采用大鼠离体MCA的VSMC静息膜电位记录实验,观察乙酰胆碱（ACh）、硫氢化钠（NaHS,H2S外源性供体）等的超极化作用。结果：ACh可使大鼠MCA的VSMC发生浓度依赖性超极化,用NO合酶抑制剂（-LNAME,3×10-5mol/L）和前列环素（PGI2）合成酶抑制剂（Indo,10-5mol/L）预处理后,ACh对大鼠MCA的VSMC仍有明显的超极化,即非NO、非PG2介导的超极化。钙激活钾通道的阻断剂四乙胺（TEA,1×10-3mol/L）或H2S合成酶（胱硫醚-γ-裂解酶,CSE）的抑制剂DL-炔丙基甘氨酸（PPG,10-4mol/L）均可明显取消这种非NO、非PG2介导的超极化。H2S供体NaHS[（10-5~10-2.5）mol/L]对大鼠MCA的VSMC产生浓度依赖性的超极化作用,而1×10-3mol/L TEA可以抑制其超极化作用。结论：大鼠MCA非NO、非PGI2介导的VSMC超极化作用,即EDHF反应可能是H2S介导的。AIM： To study the hyperpolarizing effect of hydrogen sulfide（H2S） and endothelium-derived hyperpolarizing factor（EDHF） on the resting membrane potential of vascular smooth muscle cell（VSMC） in rat middle cerebral artery（MCA）. METHODS： By using the record of resting membrane potential of VSMC in the isolated rat MCAs,the hyperpolarizing effects of acetylcholine（ACh）,NaHS were detected,respectively.RESULTS：In rat MCAs,10-7-10-4.5 mol/L ACh had significant and concentration-dependent hyperpolarizing effect on the resting membrane potential of VSMC in the absence and presence of 3×10-5 mol/L Nω-nitro-L-arginine-methyl-ester（L-NAME,an inhibitor of nitric oxide synthase） and 1×10-5 mol/L indomethacin（Indo,an inhibitor of PGI2 synthesis）.The hyperpolarizing effect of ACh in the presence of L-NAME and Indo was almost abolished by tetraethylammonium（TEA,an inhibitor of calcium-activated K＋ channels at 1×10-3 mol/L） or 1×10-4 mol/L DL-propargylglycine（PPG）,an inhibitor of endogenous H2S synthase（cystathionine-γ-lyase,CSE）.NaHS,a donor of H2S had the concentration-dependent hyperpolarizing effect on the resting membrane potential of VSMC in rat MCAs,and the hyperpolarization was markedly inhibited by 1×10-3 mol/L TEA.CONCLUSION： H2S might mediate the non-NO-non-PGI2 hyperpolarization,the so-called EDHF response on the resting membrane potential of VSMC in rat MCAs.

关 键 词：内皮源性超极化因子 硫化氢 大鼠大脑中动脉 平滑肌细胞 静息膜电位 超极化 

分 类 号：R965.2[医药卫生—药理学]