硫化氢介导的大鼠大脑中动脉的内皮源性超极化因子反应  

Hydrogen sulfide induced the endothelium-derived hyperpolarizing factor dilation in rat middle cerebral artery

作　　者：周方杰[1] 陈志武[1] 

机构地区：[1]安徽医科大学药理学教研室

出　　处：《安徽医科大学学报》2011年第8期768-771,共4页Acta Universitatis Medicinalis Anhui

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

摘　　要：目的探讨硫化氢(H2S)在大鼠大脑中动脉(MCA)上是否具有内皮源性超极化因子(EDHF)样作用。方法应用离体血管舒缩功能测定方法,检测乙酰胆碱(ACh)、硫氢化钠(NaHS)等对大鼠离体MCA的舒张作用。血管用一氧化氮(NO)合酶抑制剂(L-NAME,3×10-5mol/L)和前列环素(PGI2)合酶抑制剂(Indo,1×10-5mol/L)预处理后,用ACh诱导血管产生非NO、非PGI2舒张反应。并观察四乙胺(TEA,1×10-3mol/L)或DL-炔丙基甘氨酸(PPG,1×10-4mol/L)对这种非NO、非PGI2舒张反应的影响。结果在30 mmol/L KCl预收缩的大鼠MCA上,ACh(10-7～10-4.5mol/L)和NaHS(10-5～10-2.5mol/L,H2S供体)均可浓度依赖性舒张大鼠MCA。血管用L-NAME(3×10-5mol/L)和Indo(1×10-5mol/L)预处理后,ACh对MCA仍具有明显的舒张作用(P<0.01)。在1×10-3mol/L浓度时具有阻断钙激活钾通道作用的TEA或内源性H2S合成酶——胱硫醚-γ-裂解酶(CSE)的抑制剂PPG(1×10-4mol/L)均可明显取消ACh诱导大鼠MCA的这种非NO、非PGI2介导的舒张。结论在大鼠MCA中,ACh诱导的非NO、非PGI2舒张反应,即EDHF反应可能是H2S介导的。Objective To study whether hydrogen sulfide（H2S） induced the endothelium-derived hyperpolarizing factor（EDHF） dilation in rat middle cerebral artery（MCA） or not.Methods The relaxant effects of acetylcholine（ACh）,sodium hydrosulfide（NaHS） on isolated rat MCAs were detected by vasomotoricity experiment in vitro,respectively.Non-NO,non-PGI2 relaxation was induced by ACh in the presence of Nω-nitro-L-arginine-methyl-ester（L-NAME） and indomethacin（Indo）.The effects of tetraethylammonium（TEA,1×10-3 mol/L） or DL-propargylglycine（PPG,1×10-4 mol/L） on the non-NO,non-PGI2 relaxation were also observed.Results In the isolated rat MCAs preconstricted by 30 mmol/L KCl,ACh（10-7～10-4.5 mol/L） and NaHS（10-5～10-2.5 mol/L,a donor of H2S） had the concentration-dependent relaxation.The ACh-induced vasorelaxation was partly inhibited in the presence of 3×10-5 mol/L L-NAME and 1×10-5 mol/L Indo,but the left relaxation was still significant.ACh-induced vasorelaxation in the presence of L-NAME and Indo was almost abolished by TEA（an inhibitor of calcium-activated K＋ channels at 1×10-3 mol/L） or 1×10-4 mol/L PPG（an inhibitor of endogenous synthesis of H2S）.Conclusion In the rat MCA,ACh-induced non-NO,non-PGI2 relaxation,the so-called EDHF dilation might be mediated by H2S.

关 键 词：硫化氢 大脑中动脉 血管舒张 钾通道 钙激活 

分 类 号：R194.3[医药卫生—卫生事业管理] R329.251[医药卫生—公共卫生与预防医学]