异丙酚对兔离体气管平滑肌舒张作用机制的研究

The mechanism of propofol-induced relaxation of isolated tracheal smooth muscle from rabbit

目的探讨异丙酚在正常和炎症状态下对气管平滑肌收缩作用的影响及其机制。方法8只健康新西兰大白兔，每次试验用气栓法处死1只，每只兔制备8个气管平滑肌条，依据悬挂气管平滑肌条的营养液中处理因素不同，采用随机数字表法将气管平滑肌条随机分为8组即（每组8个）：a组（0μmol/L），b组（异丙酚300μmol／L），c组（环糊精-β10mmol／L），d组（环糊精-β10mmol／L＋异丙酚300μmol／L），c组（0μmol／L），f组（异丙酚300μmol／L），g组（环糊精-β10mmol／L），h组（环糊精-β10mmol／L＋异丙酚300μmol／L）。e，f，g，h4组气管平滑肌条浸于浓度为50μg／L肿瘤坏死因子-α溶液里，并通以95％O2和5％CO2在4℃恒温冰箱冷藏12h以供试验。用Medlab生物采集系统记录平滑肌条不同时间点张力值变化。免疫组化法测定小窝蛋白-1表达。结果与a组（1．28±0．12、1．25±0．13、1．23±0．16、1．22±0．19）比较，b组（0．86±0．13、0．61±0．11、0．51±0．17、0．51±0．18）、c组（1．18±0．15、1．08±0．13、0．98±0．15、0．89±0．16）、d组（0．98±0．12、0．84±0．14、0．80±0．14、0．78±0．17）T1。时间点张力值降低，差异有统计学意义（P〈0．05）；与b组比较c,d两组T1-4各时间点张力值高，差异有统计学意义（P〈0．05）；与e组（0．92±0．16、0．91±0．12、0．89±0．13、0．81±0．16）比较，f组（0.41±0．12、0．22±0．14、0．13±0．14、0．12±0．14）、g组（0．80±0．15、0．78±0．13、0．75±0．15、0．72±0．17）、h组（0．79±0．12、0．70±0．12、0．68±0．16、0．68±0．19）T1-4时间点张力值降低，差异有统计学意义（P〈0．05）；与f组比较g、h两组T1-4时间点张力值高，差异有统计学意义（P〈0．05）；8xe两组小窝蛋白-1为高表达；b、f两组小窝蛋白．1为低表达；c、d、g、h4组小窝蛋白-1为阴性。结论异丙酚直接舒张气管平滑肌的机制可能与其抑制小窝蛋白-1的表达有关。

Objective To explore the effect and mechanism of propofol on normal and inflammatory tracheal smooth muscles. Methods Eight healthy New Zealand white rabbit were killed by gas emboli and the tracheas were collected. Each trachea was made into eight smooth muscle strips which were immersed into different nutrient solutions. According to the nutrient solutions and the followed treatment, the strips were divided into eight groups（n=8） ： group a（0 μmol/L）, group b（300 μmol/L）, group c（cyclodextrins-beta 10 mmol/L）, group d（cyclodextrins-beta 10mmol/L＋propofol 300 μmol/L）, group e（0 μmol/L）, group f （propofol 300 μmol/L）, group g （eyelodextrins-beta 10 mmol/L）, group h （ cyclodextrins-beta 10 mmol/L＋propofol 300 μmol/L）. The strips in e, f, g group and h group were bathed in a solution of TNF-α （50 μg/L） in the presence of 95% 02 and 5% CO2 at 4 ℃ for 12 h. The tension of the strips at different time points were recorded with Medlab biological acquisition system. Immunohistochemistry determined the expression of eaveolin-1. Results The tension at T1-4 of group b （0.86±0.13, 0.61±0.11, 0.54±0.17, 0.51±0.18）, group e（1.18±0.15, 1.08±0.13, 0.98±0.15, 0.89±0.16）, group d（0.98±0.12, 0.84±0.14, 0.80±0.14, 0.78±0.17）was lower than of group a （1.28±0.12, 1.25±0.13, 1.23±0.16, 1.22±0.19, P〈0.05）. The tension at T1-4 of group c, d was higher than of group b （P〈 0.05）. The tension at T1-4 of group f （0.41±0.12, 0.22±0.14, 0.13±0.14, 0.12±0.14）, group g （0.80±0.15, 0.78±0.13, 0.75±0.15, 0.72±0.17）, group h（0.79±0.12, 0.70±0.12, 0.68±0.16, 0.68±0.19） was lower than of group e（0.92±0.16, 0.91±0.12, 0.89±0.13, 0.81±0.16, P〈0.05）. The tension at T1-4 of group g and h was higher than of group f （P〈0.05）. The expression of caveolin-1 protein presented high （＋＋＋）. In group a and e, low（＋） in group b and f and appeared negative in group c, d, g and h. Conclusions The study showed that the direct relaxant effect of propofol on tracheal smooth muscle might be related to the inhibition of caveolin-1 protein expression.