缺氧性脑动脉收缩中15-羟二十碳四烯酸对Kv2.1的作用

Effect of 15-hydroxyeicosatetrienoic acid on Kv2.1 channel in cerebral vasoconstriction induced by hypoxia

目的研究在缺氧性脑动脉收缩中15-羟二十碳四烯酸(15-hydroxyeicosatetrienoic acid,15-HETE)对Kv2.1通道的表达是否具有调控作用。方法 24只健康Wistar大鼠随机分为3组(n=8):A组为对照组,吸大气,FiO2(氧浓度)为21%;B组为缺氧组,将大鼠置于FiO2为12%的缺氧箱中;C组为15-HETE组,吸大气,FiO2为21%。9天后将大鼠全部处死,游离直径为0.5～1.0 mm的脑动脉;将游离的脑动脉于恒温浴槽中水浴2 h,C组浴液中加入15-HETE,使其浓度为10-6mol/L。分别采用RT-PCR和Western blot技术检测脑动脉上Kv2.1通道mRNA和蛋白质的表达情况。结果①缺氧组及15-HETE组脑动脉上Kv2.1通道mRNA的表达明显低于对照组(P<0.05);②缺氧组及15-HETE组脑动脉上Kv2.1通道蛋白质的表达明显低于对照组(P<0.05)。结论缺氧可能是通过15-HETE这一介导因子抑制Kv2.1通道,减少脑动脉上功能性Kv2.1通道的数量,导致脑动脉收缩。

Objective To investigate whether 15-hydroxyeicosatetrienoic acid（15-HETE）can regulate the expression of Kv2.1 channel in cerebral vasoconstriction induced by hypoxia.Methods Twenty-four healthy Wistar rats were randomly divided into 3 groups（n=8）： group A（control group） with normal oxygen supply（FiO2 21%）,group B（hypoxia group） with low flow oxygen supply（FiO2 12%） and group C（10-6 mol/L 15-HETE group）.Nine days later,all of the rats were killed and the arteries which were 0.5～1.0 mm in diameter were excised.Then the cerebral arteries were put into thermostatic bath for 2 h,and 15-HETE was added to group C with concentration of 10-6 mol/L.The expression of Kv2.1 channel mRNA and protein in each group were detected by using RT-PCR and Western blot analysis respectively.Results ① The expression of Kv2.1 channel mRNA was obviously lower in hypoxia group and 15-HETE group than that in control group（P0.05）.② The expression of Kv2.1 channel protein was obviously lower in hypoxia group and 15-HETE group than that in control group（P0.05）.Conclusion Hypoxia may block Kv2.1 channel via 15-HETE mediated mechanism,leading to decrease of numbers of functional Kv2.1 channel in cerebral arteries and cerebral vasoconstriction.