异丙酚对哮喘豚鼠离体气管平滑肌张力的作用

Effect of propofol on tracheal smooth muscle isolated from guinea pigs with induced asthma

目的 探讨异丙酚对哮喘豚鼠离体气管平滑肌张力的作用及其作用机制。方法 48只健康豚鼠随机分为哮喘组(n=28)和正常组(n=20),卵蛋白致敏法建立哮喘豚鼠模型,每只豚鼠制备5-7个气管平滑肌环,依据悬挂平滑肌环的营养液中处理因素不同将气管平滑肌环随机分为control亚组、10％Intralipid亚组、10、30、100、300μmol/L Propofol亚组,通过与气管环相连的力-位移换能器记录其张力变化,采用悬挂平滑肌环的营养液中无Ca2+的方法测定异丙酚对Ryanodine受体介导的细胞内Ca2+释放的影响。结果 (1)100μmol/L异丙酚显著舒张哮喘豚鼠静息气管平滑肌。四种浓度异丙酚对乙酰胆碱所致气管平滑肌收缩呈剂量依赖的舒张作用。(2)四种浓度异丙酚预适应可剂量依赖性抑制乙酰胆碱所致气管平滑肌收缩。哮喘组30μmol/L异丙酚预适应使乙酰胆碱所致的气管平滑肌依内钙性收缩由(37.7±2.8)％降为(27.7±1.9)％,依外钙性收缩由(62.3±4.5)％降为(51.5±3.5)％,与control亚组比较差异有显著性(P<0.01)。(3)四种浓度异丙酚抑制乙酰胆碱所致气管平滑肌依内钙性收缩作用,与无Ryanodine作用组比较,差异无显著性(P>0.05)。结论临床相关浓度异丙酚预适应显著抑制乙酰胆碱收缩哮喘豚鼠离体气管平滑肌的作用,其作用机制与Rvanodine受体介导?

Objective To investigate the effect of different concentrations of propofol on tracheal smooth muscle (TSM) isolated from guinea pigs with induced asthma and the underlying mechanism. Methods Forty-eight guinea pigs of either sex weighing 150-200 g were randomly divided into 2 groups : normal group ( n = 20) and asthma group ( n = 28). Asthma was induced with ovoglobulin. The animals were sacrificed by a blow to the head without anesthesia. Trachea was immediately removed and cut into tracheal rings (3-5 mm in length) . 5-7 tracheal rings were prepared from each animal and suspended in organ bath filled with oxygenated (95% O2 , 5% CO2 ) KHB and stretched to an optimal resting tension which was measured by using a force-displacement transducer with a pen recorder. The two groups were further divided into six subgroups : control subgroup, 10 % intralipid subgroup and 4 propofol subgroups (10, 30, 100, 300μmol·L-1). The effect of different concentrations of propofol and their interaction with acetylcholine ( Ach ) and ryanodine on contraction of TSM were measured. Results (1) Effect of propofol on resting tension of TSM : in normal group propofol had no effect on TSM resting tension, while in asthma group propofol reduced TSM resting tension in a dose-dependent manner. 10% intralipid contracted TSM slightly and insignificantly as compared with control subgroup. (2) Effect of propofol on TSM contraction induced by Ach : propofol inhibited TSM contraction induced by Ach in a dose-dependent manner in both normal and asthma group. (3) Effect of propofol preconditioning on TSM contraction induced by Ach : pretreatment with propofol 100 and 300μmol·L-1 significantly inhibited TSM contraction induced by Ach in both normal and asthma group as compared with control subgroup. Pretreatment with even propofol 30μmol·L-1 was effective in asthma group. (4) There was no significant difference in propofol-inhibition of TSM contraction induced by Ach with or without ryanodine. Conclusion Pretreatment with clinical doses of propofol can significantly inhibit TSM contraction induced by Ach in guinea pigs with asthma and ryanodine receptor-mediated smooth muscle intracellular Ca2+ release is not involved.