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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 relaxation of isolated tracheal smooth muscle in asthmatic rats and its relationship with large-conductance calcium-activated-potassium channel (BKca) and protein kinase G (PKG) signal transduction system. Methods Sprague-Dawley rats were prepared by intraperitoneal injection of ovalbumin (OVA) and continuous dripping nasal method. Two to three extubated tracheal strips were prepared in each rat. The rats were treated with 10-2, 10-1, × 10-1, 10 × 10-1mg / mL of ketamine on the tension of tracheal ring of asthmatic rats precontracted with acetylcholine. After incubating with BKca-specific inhibitor IBTX (3 × 10-6M) or PKG inhibitor KT-5823 (2 × 10-6M), the effects of 4 × 10-1mg / mL ketamine on the extubation of asthmatic rats Relaxation of the tension of the ring muscle. Results The diastolic effects of Ket at 10-2, 10-1, 4 × 10-1 and 10 × 10-1 mg / mL on the tracheal rings in asthmatic rats were 4.61% ± 1.85% and 14.02% ± 3.96%, respectively. 70.10% ± 11.12%, 100%. The diastolic effects of each concentration were statistically significant (all P <0.05). After incubation with IBTX or KT-5823, the relaxation of tracheal smooth muscle was 51.32% ± 8.27%, 52.15% ± 7.94%, respectively, with Ketokinase 4 × 10-1 mg / mL, compared with 70.10% ± 11.12 %) Were statistically significant (P <0.05). Conclusions Ketamine can relieve the airway smooth muscle of asthmatic rats in a dose-dependent manner. Its mechanism may be related to BKca and PKG signal transduction system.