BKCa和PKG在氯胺酮舒张哮喘大鼠离体气管平滑肌中的作用  

Role of large-conductance Ca2＋ -activated K＋ channels and protein kinase G in ketamine-induced isolated tracheal smooth muscle relaxation in rats with asthma

作　　者：周述芝[1] 马楠[2] 李妙龄[3] 杨艳[3] 王晓斌[1] 魏继承[1] 

机构地区：[1]泸州医学院附属医院麻醉科,646000 [2]新疆医科大学第一附属医院麻醉科 [3]泸州医学院心肌电生理学实验室

出　　处：《中华麻醉学杂志》2013年第3期314-316,共3页Chinese Journal of Anesthesiology

基　　金：基金项目：国家自然科学基金（81271478）;四川省卫生厅资助项目（07005）

摘　　要：目的评价大电导钙激活钾通道（BKCa）和蛋白激酶G（PKG）在氯胺酮舒张哮喘大鼠离体气管平滑肌中的作用。方法健康sD大鼠，体重250～300g，采用卵蛋白致敏法建立哮喘模型，取哮喘大鼠15只，每只大鼠制备2～3条离体气管环。取哮喘大鼠离体气管环36条，采用随机数字表法，将其分为3组（n=12）：氯胺酮处理组（AK组）、BKCa阻断剂IBTX＋氯胺酮处理组（AKI组）和PKG抑制剂KT-58232＋氯胺酮处理组（AKK组）；AK组采用0．1mmol／L乙酰胆碱预收缩大鼠气管环达稳态后，用0．4g／L氯胺酮孵育15min；AKI组用乙酰胆碱和氯胺酮孵育前，用3μmol／LIBTX孵育30min；AKK组用人乙酰胆碱和氯胺酮孵育前，用2μmol／LKT-5823孵育30min；采用气管环相连的力一位移换能器测定气管环舒张幅度。结果与AK组比较，AKI组和AKK组大鼠离体气管平滑肌舒张幅度降低（P〈0．05）。结论氯胺酮可通过激活BKCa和PKG信号通路舒张哮喘大鼠离体气管平滑肌。Objective To investigate the role of large-conductance Ca2＋ -activated K＋ （BKCa） channels and protein kinase G （PKG） in ketamine-induced isolated tracheal smooth muscle relaxation in rats with asthma. Methods Healthy Sprague-Dawley rats, weighing 250-300 g, were used in this study. Asthma was induced with egg albumin. Thirty-six tracheal rings of 15 rats in which asthma model was successfully established were randomly divided into 3 groups （n = 12 each） ： ketamine treatment group （group AK）, IBTX （BKCa channel blocker） ＋ ketamine treatment group （group AKI）, and KT-58232 （PKG inhibitor） ＋ ketamine treatment group （group AKK）. Tracheal rings were suspended in an organ bath filled with oxygenated Kreb＇s solution at 36.5-37.5 ℃ . In group AK, the tracheal rings were precontracted with acetyleholine 0.1 mmol/L, and the rings were then exposed to ketamine 0.4 g/L for 15 min. In group AKI, before acetyleholine and ketamine were added to the solution, the rings were pretreated with IBTX 3 μmol/L for 30 min. In group AKK, before acetyleholine and ketamine were add- ed to the solution, the rings were pretreated with KT-5823 2 μmol/L for 30 rain. The tension of rings was measured by using a force-displacement transducer. Results The amplitude of relaxation of isolated tracheal smooth muscle was significantly decreased in groups AKI and AKK as compared with group AK （ P 〈 0. 05 ）. Conclusion Ket- amine induces isolated tracheal smooth muscle relaxation through activating BKCa channels and PKG signaling pathway in rats with asthma.

关 键 词：大电导钙激活钾通道 蛋白激酶类 氯胺酮 肌细胞 平滑肌 气管 哮喘 

分 类 号：R285.5[医药卫生—中药学]