氯胺酮对哮喘大鼠离体气管平滑肌的舒张作用及机制探讨

Effects and mechanism of ketamine on tracheal smooth muscle isolated from rats with induced asthma

目的观察氯胺酮舒张哮喘大鼠离体气管平滑肌的作用及其与大电导钙激活钾通道(BKca)及蛋白激酶G(PKG)信号传导系统的关系。方法将SD大鼠以卵蛋白(OVA)腹腔注射法及连续滴鼻法制备哮喘大鼠模型,每只大鼠制备2～3条离体气管条,观察以10-2、10-1、4×10-1、10×10-1mg/mL的氯胺酮对乙酰胆碱预收缩后的哮喘大鼠气管环张力的影响。然后用BKca特异性阻断剂IBTX(3×10-6M)或PKG抑制剂KT-5823(2×10-6M)孵育后,观察4×10-1mg/mL的氯胺酮对哮喘大鼠离体气管环肌张力的舒张作用。结果浓度分别为10-2、10-1、4×10-1及10×10-1mg/mL的Ket对哮喘大鼠气管环的舒张效应分别为4.61%±1.85%、14.02%±3.96%、70.10%±11.12%,100%,各浓度间舒张效应比较有统计学差异(P均<0.05)。用IBTX或KT-5823孵育后,4×10-1mg/mL的Ket使气管平滑肌的舒张作用分别为51.32%±8.27%、52.15%±7.94%,与无阻滞剂孵育组(70.10%±11.12%)比较有统计学差异(P<0.05)。结论氯胺酮对哮喘大鼠气管平滑肌有舒张作用并呈剂量依赖性,其作用机制可能与BKca和PKG信号传导系统有关。

Objective To investigate the effects of ketamine on tracheal smooth muscle isolated from rats with induced asthma and explore its relationship with large-conductance Ca2＋-activated-K＋ channel（BKca） or protein kinase G（PKG） signal pathway.Methods Peritoneal injection and continuous nose-dripping with ovalbumin（OVA） in SD rats were used for making asthmatic model,2-3 isolated tracheal rings were made from each rats.The effects of ketamine in 10-2,10-1,4×10-1 and 10×10-1 mg/mL on the tracheal rings pre-constricted by acetylcholine（Ach） were determined by cumulative addition method;Then the tracheal ring were pretreated with Ca2＋-activated-K＋ channel blocker（IBTX） or protein kinase G blocker（KT-5823）,the effect of 4×10-1 mg/mL ketamine was measured.Results Ketamine in 10-2,10-1,4×10-1 and 10×10-1 mg/mL relaxed tracheal rings of asthmatic rats in a dose dependent manner,with the relaxation effect of（4.61±1.85）%,（14.02±3.96）%,（70.10±11.12）%,100%.Pretreatment to the rings with IBTX（3×10-6 M） or KT-5823（2×10-6 M） attenuated the relaxation effect of Ket（4×10-1 mg/mL）,which was different compared with control group of（70.10±11.12）%,P0.05.Conclusion The dilatation effects of ketamine on the isolated asthmatic rat tracheal ring are dose dependent.Themechanism may be related to Ca2＋-activated-K＋ channel and PKG signal pathway.