内源性内皮衍生超极化因子对缺氧/再给氧致大鼠海马神经细胞凋亡的抑制作用  

The inhibition of endogenous endothelium-derived hyperpolarizing factor on hypoxia /reoxygenation-induced apoptosis of hippocampal neurons in rats

作　　者：余小蒙[1] 吴剑[1] 陈志武[1] 郭岩[1] 

机构地区：[1]安徽医科大学药理学教研室,合肥230032

出　　处：《安徽医科大学学报》2014年第9期1258-1262,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81173596);安徽省自然科学基金(编号:11040606M196)

摘　　要：目的研究乙酰胆碱(ACh)诱导内源性内皮衍生超极化因子(EDHF)对缺氧/再给氧大鼠海马神经细胞凋亡的影响。方法取原代培养的大鼠海马神经细胞制备缺氧/再给氧损伤模型;大鼠大脑中动脉(MCA)血管段用一氧化氮合酶抑制剂NG-nitro-L-argininemethyl ester(L-NAME)和前列环素抑制剂indomethacin(Indo)预处理,用ACh诱导血管内皮细胞合成释放内源性EDHF;分别用流式细胞仪法和Hoechst荧光法检测海马神经元凋亡。结果流式细胞仪法和Hoechst荧光法检测均表明假缺氧组海马神经细胞的凋亡率很低,分别为3.1%和2.2%左右,而缺氧/再给氧的模型组细胞凋亡率有显著升高;与缺氧/再给氧模型组相比,内皮完整血管段合用1μmol/L ACh或合用1μmol/L ACh、30μmol/L L-NAME及10μmol/L Indo均可明显抑制缺氧/再给氧所致的细胞凋亡,而单用ACh或内皮完整的血管或ACh合用去内皮的血管段对细胞凋亡无明显影响。结论 ACh诱导大鼠脑血管内皮细胞释放的内源性EDHF对缺氧/再给氧海马神经细胞凋亡有明显的抑制作用。Objective To study the effect of acetylcholine （ACh） induced endogenous endothelium-derived hyper- polarizing factor （ EDHF ） on apoptosis of rat hippoeampal neurons. Methods Primarily cultured hippocampal neu-rons were insulted by hypoxia/reoxygenation （H/R） , and EDHF from rat MCA segment was induced by acetylcho- line （ACh） in the presence of NG-nitro-L-argininemethyl ester （L-NAME） and indomethacin （ Indo）, the rate of hippocampal neuron apoptosis was detected by Hoechst staining and flow cytometry （FC） methods. Results Ex- aminations of FC and Hoechst staining showed that the apoptosic rate of rat hippocampal neurons was very low in the sham group, only about 3.1% and 2.2% respectively,but H/R injury caused an obvious increase of apoptosis of rat hippocampal neurons. Co-adminstration of endothelium-intact MCA segment with 1μmol/L ACh or co-admin- stration of endothelium-intact MCA segment with 1 μmol/L ACh ＋ 30 μmol/L L-NAME ＋ 10 μmol/L Indo markedly inhibits H/R-induced apoptosis of rat hippocamal neurons. However, administration of ACh or MCA seg- ment separately had not effect on H/R-induced apoptosis of rat hippocamal neurons, and neither did co-adminstra- tion of endothelium-denuded MCA segment with ACh. Conclusion Endogenous EDHF released from ACh-induced vascular endothelial cells significantly inhibits H/R-caused apoptosis of rat primarily cultured neurons

关 键 词：内皮依赖性超极化因子 海马神经细胞 细胞凋亡 缺氧/再复氧 

分 类 号：R743[医药卫生—神经病学与精神病学] R322.81[医药卫生—临床医学]