15-KETE 对慢性缺氧大鼠肺动脉平滑肌细胞钾离子通道的作用
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1. 哈尔滨医科大学第二临床医学院药学部,哈尔滨 150086;2. 哈尔滨医科大学第二临床医学院实验动物中心,哈尔滨 150086;3. 哈尔滨医科大学药学院,哈尔滨 150086

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Effect of 15-KETE on Voltage-gated K + Current in the Intrapulmonary Arterial Smooth Muscle Cells of Chronic Hypoxic Rats
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1. The Second Affiliated Hospital,The Department of Pharmacy,Harbin Medical University,Harbin 150086,China;2. Animal Experiment Center of the Second Affiliated Hospital,Harbin Medical University,Harbin 150086,China;3. Colledge of Pharmacy,Harbin Medical University,Harbin 150086,China

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    摘要:

    目的 观察 15-酮基二十 碳 四 烯 酸(15-ketoeicosatetraenoic acid,15-KETE) 对缺氧大鼠肺动脉平滑肌细胞( pulmonary arterial smooth cells,PASMCs)膜电压门控钾离子通道的活性的影响。方法 将 12 只雄性 SD 大鼠随机分成对照组和缺氧组,每组 6 只。采用急性酶分离法(胶原酶Ⅰ型和弹性酶) 获得 SD 大鼠单个 PASMCs,应用全细胞膜片钳记录方法,研究 15-KETE 对两组大鼠膜电位( Em)、膜电容( Cm)、电压门控钾电流( IKv) 的 影 响。结果 (1 ) 慢性缺氧使大鼠 PASMCs 的 Em 显 著 去 极 化 ( P < 0. 05,n = 6 ) ,明 显 地 抑 制 了 大 鼠 PASMCs 的 IKv(P < 0. 01,n = 6) ,对大鼠 PASMCs 的 Cm 无影响;(2)较高浓度的 15-KETE (1 × 10 - 7 mol /L、1 × 10 - 6 mol /L) 可使慢性缺氧大鼠 PASMCs 去极化;(3)15-KETE (1 × 10 - 8 mol /L ~ 1 × 10 - 6 mol /L) 可浓度依赖性地抑制慢性缺氧大鼠 PASMCs 的 IKv;(4)较高浓度 15-KETE (1 × 10 - 7 mol /L、1 × 10 - 6 mol /L)对缺氧 PASMCs IKV 的平均阻抑率显著高于常氧 PASMCs。结论 缺氧未改变 15-KETE 引大鼠 PASMCs 去极化及浓度依赖抑止 IKv 的 特 性,且 缺 氧 可 能改变了 PASMCs 对 15-KETE 的敏感性。

    Abstract:

    Objective To observe the effect of 15-KETE on voltage-gated K + (Kv) current in the intrapulmonary arterial smooth muscle cells ( PASMCs) of chronic hypoxic rats. Methods Twelve male SD rats matched with age and body weight were randomly divided into control and hypoxic groups. Single PASMCs were obtained with acute enzyme ( collagenⅠplus elastase) dispersing method. Using whole cell path-clamp technique in freshly isolated rat PASMCs from normoxic and hypoxic rats,the effect of 15-KETE on Kv current was recorded. Results ( 1 ) The resting membrane potential (Em) in PASMCs from chronic hypoxic rats was significantly depolarized to compared with that from normoxic control rats(P < 0. 05,n = 6) . The chronic hypoxia significantly inhibited the IKv of PASMCs from rats ( P < 0. 01,n =6) ,but did not alter the membrane capacitance (Cm) of PASMCs from rats. (2) The higher concentration of 15-KETE(1× 10 - 7 mol /L,1 × 10 - 6 mol /L) depolarized PASMCs from chronic hypoxic rats. (3) 15-KETE(1 × 10 - 8 mol /L ~ 1 ×10 - 6 mol /L) caused concentration-dependent inhibition of IKv in PASMCs from chronic hypoxic rats. ( 4 ) The percent inhibition that the higher concentration of 15-KETE(1 × 10 - 7 mol /L,1 × 10 - 6 mol /L) caused from chronic hypoxic rats was greater than that from normoxic control rats. Conclusions Hypoxia did not change the effect of 15 - KETE on the passive electrical properties of PASMCs. In both normoxic and hypoxic PASMCs,exogenous 15-KETE could cause concentration-dependent inhibition Kv current,and the inhibition of Kv current from hypoxic rats were greater than that from normoxic rats in higher concentration ( 1 × 10 - 7 mol /L ~ 1 × 10 - 6 mol /L) . Hypoxia might alter the sensitivity of PASMCs to 15-KETE.

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张一飞,郭守利,刘 晔,朱大岭.15-KETE 对慢性缺氧大鼠肺动脉平滑肌细胞钾离子通道的作用[J].中国比较医学杂志,2011,21(1):27~32.

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  • 收稿日期:2010-05-31
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  • 在线发布日期: 2025-11-06
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