目的：研究右美托咪定对人离体肺内小动脉对血管收缩剂五羟色胺的张力变化和作用机制。方法本研究人体标本来源于因肺肿瘤行肺叶切除手术的病人，选取肿瘤周围正常肺组织作为实验标本，分离人肺内小动脉，制备血管环，每一个病人提供1~4个血管环，同一个病人来源的血管环纳入不同的实验组别。采用微血管张力测定技术，观察孵育0.3~3 nmol/L浓度的右美托咪定后血管对五羟色胺收缩的张力变化，并观察去内皮、加入L-NAME、育亨宾或吲哚美辛对右美托咪定作用的影响，从而探讨其作用机制。结果0.1~100 nmol/L的右美托咪定对静息状态下内皮完整的肺内小动脉张力无明显影响。5-HT对内皮完整的人离体肺内小动脉产生浓度依赖性的收缩作用，pD2为6.11±0.05，Emax为（102.10±1.96）%；0.3~3 nmol/L的右美托咪定能减弱5-HT对内皮完整的肺内小动脉环的收缩作用，并呈浓度依赖性，3 nmol/L的右美托咪定组pD2为5.94±0.03，Emax为（79.96±1.31）%。5-HT对去除内皮的人离体肺内小动脉也能产生浓度依赖性的收缩作用，pD2为6.10±0.07，Emax为（107.40±3.20）%；但右美托咪定不能减弱5-HT对去除内皮的人肺内小动脉环的收缩作用。在内皮完整的肺内小动脉环上加入100μmol/L的L-NAME或50 nmol/L的育亨宾孵育后，右美托咪定减弱5-HT对人肺内小动脉环的收缩作用被消除；加入5μmol/L的吲哚美辛则对右美托咪定减弱5-HT收缩作用无明显影响。结论右美托咪定可能通过激动血管内皮的α2肾上腺素受体，释放NO从而抑制五羟色胺诱导的肺内小动脉收缩。%Objective To investigate the effect of dexmedetomidine on 5- HT- induced constrictions of isolated human intrapulmonary arteries and explore the mechanisms. Methods Lung tissue was obtained from patients undergoing surgery for lung carcinoma. Intrapulmonary arteries were dissected and cut into rings, which were mounted in a Multi Myograph system to determine the effect of dexmedetomidine (0.3-3 nmol/L) on 5-HT-induced vasoconstractions. The influences of the endothelium removal and various drugs including L-NAME, yohimbine and indomethacin were tested on the effects of dexmedetomidine. Results Dexmedetomidine (0.1-100 nmol/L) did not obviously affect the resting tension of endothelium-intact human intrapulmonary arteries. 5- HT induced concentration- dependent contraction in endothelium- intact intrapulmonary arteries[pD2:6.11 ± 0.05, Emax:(102.10 ± 1.96)%]. In the rings with intact endothelium, dexmedetomidine (0.3-3 nmol/L) significantly attenuated the Emax and pD2 of 5-HT-induced vasoconstriction[pD2:5.94±0.03, Emax:(79.96±1.31)%]. 5-HT also induced concentration-dependent contraction in endothelium-denuded intrapulmonary arteries [pD2: 6.10 ± 0.07, Emax:(107.40 ± 3.20)%]. Dexmedetomidine produced no significant effects on the rings with denuded endothelium. The effects of dexmedetomidine on 5-HT-induced vasoconstriction was suppressed by L-NAME and yohimbine, but not by indomethacin. Conclusion Dexmedetomidine can inhibit 5-HT-induced vasoconstriction of isolated human intrapulmonary arteries probably throughα2-adrenergic acceptor and NO released from the endothelium.
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