4-氨基吡啶调节大鼠低氧高二氧化碳性肺血管收缩时ERK1/2信号通路的作用  

4-Aminopyridione Regulate ERK1 /2 Signal Pathway During Hypoxic Hypercapnia Pulmonary Vasoconstriction in Rats

作　　者：马迎春[1] 郑梦晓 黄林静[1] 王淑君 汪洋[1,3] 王万铁[1,3] 

机构地区：[1]温州医科大学基础医学院病理生理学教研室,浙江省温州市325035 [2]赤峰上京内分泌专科医院内分泌科,内蒙古赤峰市024000 [3]温州医科大学缺血再灌注损伤研究所,浙江省温州市325035

出　　处：《中国动脉硬化杂志》2014年第9期897-901,共5页Chinese Journal of Arteriosclerosis

基　　金：卫生部科学研究基金-浙江省医药卫生重大科技项目(WKJ2009-2-030);浙江省中医药重点学科建设计划项目(2012-XK-A28)

摘　　要：目的探讨电压依赖性钾离子通道(KV)及细胞外信号调节激酶1/2(ERK1/2)信号通路在大鼠低氧高二氧化碳性肺血管收缩(HHPV)中的作用。方法制作正常SD大鼠离体二级肺动脉环,在常氧及低氧高二氧化碳条件下分别观察肺动脉环的张力变化。在急性低氧高二氧化碳条件下,分别用KV阻断剂4-氨基吡啶(4-AP)、ERK1/2信号通路抑制剂U0126、4-AP+U0126孵育二级肺动脉环,测定各组血管环的张力值。结果在急性低氧高二氧化碳条件下:1肺动脉环呈现双向性的收缩(与常氧状态比较,P<0.05);2经4-AP孵育的二级肺动脉环收缩幅度增强,尤其是Ⅱ期持续收缩(P<0.05);3U0126能使4-AP所致的二级肺动脉环的Ⅱ期持续收缩幅度显著降低(P<0.05)。结论 4-AP可增强大鼠的HHPV,而U0126能使4-AP所致的二级肺动脉环的Ⅱ期持续收缩幅度显著降低,提示ERK1/2信号通路可能在电压依赖性钾离子通道调节大鼠HHPV的机制中发挥重要作用。Aim To investigate the role and significance of voltage dependent K＋channel（ KV） and ERK1/2signal pathway in the pathological process of hypoxia hypercapnia pulmonary vasoconstriction（HHPV） in rats. Methods We made the second pulmonary artery rings of SD rats in vitro,and divided the rings randomly into： control group,hypoxia hypercapnia group,hypoxia hypercapnia ＋ DMSO incubation group（HD group）,hypoxia hypercapnia ＋ 4-aminopyridione（4-AP） incubation group（4-AP group）,hypoxia hypercapnia ＋ U0126 incubation group（ U0126 group）,hypoxia hypercapnia ＋ 4-AP ＋ U0126 incubation group（4-AP ＋ U0126 group）. Under acute hypoxia hypercapnia condition,we observed the effects of the three stages of HHPV incubated by 4-AP or the combined application of 4-AP and U0126. At the same time,the values of rings’ tension changes were recorded. Results Under the acute hypoxia hypercapnia condition,we observed a biphasic pulmonary artery contractile response; The second pulmonary artery rings were incubated by 4-AP which phase Ⅱ persistent vasoconstriction were enhanced compared with the HD group（ P 〈 0. 05）; U0126 can significantly relieve the phase Ⅱ persistent vasoconstriction created by 4-AP（P 〈 0. 05）. Conclusion The blocker of voltage dependent K＋channel-4-AP enhanced HHPV,U0126 can significantly relieve the phase Ⅱ persistent vasoconstriction created by 4-AP,which pointed out that the ERK1 /2 signal pathway’s participation may be one of the important mechanisms of KV’s regulation to the process of HHPV in rats.

关 键 词：低氧高二氧化碳 细胞外信号调节激酶1/2 电压依赖性钾离子通道 4-氨基吡啶 

分 类 号：R363[医药卫生—病理学]