氯吡格雷对减压病的预防作用

The protection of clopidogrel in a rat model of decompression sickness

目的不安全减压产生的气泡导致血小板凝集、活化,是减压病产生的主要原因。氯吡格雷可通过抑制纤维蛋白原和二磷酸腺苷(adenosine diphosphatase,ADP)结合而抑制血小板聚集。该研究拟探讨氯吡格雷对快速上浮脱险所致减压病的预防作用,并探讨其干预机制。方法 111只雄性SD大鼠,分为正常组对照(20只)、减压病组(46只)和减压病氯吡格雷干预组(45只)。减压病组置于脱险舱内,以2t/4的指数速率快速加压至1.5 MPa,加压及停留时间共4.5 min,以3 m/s的速度匀速减压。出舱后30 min内观测大鼠死亡率、行为学改变。分析肺脏病理表现及湿干比,外周血白细胞及血小板计数,流式细胞术检测外周血活化血小板表达率,免疫组化检测肺组织中CD41的表达率。结果发现氯吡格雷可有效降低快漂减压病的死亡率(减压病+氯吡格雷组为11/45,减压病组为28/46,P<0.01)。氯吡格雷可减轻肺组织损伤、降低肺组织湿/干比、减少肺组织中血小板及白细胞聚集、降低外周血中白细胞数、活化血小板比例。结论氯吡格雷可通过降低血小板的聚集、活化,减少炎性细胞的激活,对减压病起到预防作用。

Objective Platelet aggregation,activation induced by bubbles is the main cause of decompression sickness.Clopidogrel（Clo） can decrease platelet aggregation through inhibiting the bind of fibrinogen and ADP.This study is designed to find if Clopidogrel can paly a protective role in decompression sickness and explore the intervention mechanism.Methods Totally 111 male SD rats divided into 3 groups：normal control group（n = 20）,decompression sickness（DCS）group（n = 46）,and DCS ＋ Clo（Clopidogrel） treated decompression sickness（DCS ＋ Clo） group（n = 45）.The rats in DCS and DCS ＋ Clo group were placed in chamber and compressed to 1.5 MPa at speed of 2^t/4,the time of compression and residence was 4.5 min totally,then decompressed to surface at a speed of 3 m/s.The mortality and behavioral of rats were observed within 30 min post decompression.The pathology and the wet/dry ratio of lung,WBC and platelet counts in peripheral blood,the expression of activated platelets,and immunohistochemical detection of lung tissue CD41 expression were also been tested.Results We found Clo reduces the DCS mortality risk（mortality rate：11/45 in DCS ＋ Clo group vs 28/46 in DCS group,P〈0.01）.Clo reduced the lung injury,the wet/dry ratio of lung,the accumulation of platelet and leukocyte in lung,the WBC counts and activated platelets in peripheral blood.Conclusion Clo can play a protective role in decompression sickness through reducing post-decompression platelet consumption and activation,decreasing the activation of leukocytes.