硫化氢对FeCl3诱导的小鼠颈动脉血栓模型中凝血和纤溶活性的影响

摘要

目的:探讨外源性硫化氢(H2 S)对三氯化铁(FeCl3)诱导的小鼠颈动脉血栓模型凝血和纤溶活性的影响.方法:本实验分为空白对照组、模型组、不同浓度(12.5、25和50μmol/kg)的硫氢化钠(NaHS,H2 S供体)处理组和30 mg/kg氯吡格雷(clopidogrel,阳性对照).不同浓度NaHS腹腔注射及硫酸氢氯吡格雷灌胃给药处理3 d后,采用10%FeCl3诱导小鼠颈动脉血栓模型.取各组颈动脉制成冰冻切片后,HE染色观察血栓形成及血管病理变化;对形成的血栓重量进行测量,计算血栓形成抑制率;采用血凝仪检测血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)和纤维蛋白降解产物(FDP)的变化;ELISA法检测血浆中血栓烷素B2(TXB2)、6-酮-前列腺素F1α(6-keto-PGF1α)和纤溶酶原活化抑制剂(PAI)的含量.结果:与模型组相比,NaHS剂量依赖性地抑制小鼠颈动脉血栓的形成;NaHS处理可延长血栓模型中PT和APTT,减少FIB含量,增加FDP含量;NaHS处理能够降低颈动脉血栓模型中TXB2及PAI含量,恢复6-keto-PGF1α含量,并且6-keto-PGF1α/TXB2与血栓重量呈负相关.结论:硫化氢通过抑制机体凝血功能并激活纤溶活性而抑制FeCl3诱导的颈动脉血栓形成.%AIM:To explore the influence of exogenous hydrogen sulfide ( H2 S) on coagulation and fibrinoly-sis in ferric chloride ( FeCl3 )-induced mouse carotid artery thrombosis .METHODS: The mice were divided into sham control group, model group, different concentrations (12.5, 25 and 50μmol/kg) of sodium hydrosulfide (NaHS, H2S do-nor) groups and 30 mg/kg clopidogrel ( positive control ) group.Intraperitoneal injection of NaHS at different concentra-tions and oral administration of clopidogrel bisulfate were performed for 3 d prior to FeCl 3-induced carotid artery thrombo-sis.The frozen sections of the carotid artery were collected to perform HE staining , and the thrombus pattern and the chan-ges of vascular pathology were observed .The thrombus was weighed to calculate thrombosis inhibitory rate .Prothrombin time ( PT) , activated partial thromboplastin time ( APTT) , fibrinogen ( FIB) and fibrinogen degradation product ( FDP) in the mice were also measured by a coagulometer .The plasma levels of thromboxane B 2 ( TXB2 ) , 6-keto-prostaglandin F 1α(6-keto-PGF1α) and plasminogen activator inhibitor (PAI) were detected by ELISA.RESULTS: Compared with model group, NaHS dose-dependently inhibited the formation of carotid artery thrombus .NaHS treatment reduced the contents of TXB2 and PAI, and recovered 6-keto-PGF1αcontent in thrombosis model group .In NaHS treatment groups , 6-keto-PGF1α/TXB2 and thrombus weight was negatively correlated .NaHS treatment prolonged PT and APTT , reduced the content of FIB, but increased the level of FDP in thrombosis model group .CONCLUSION:Hydrogen sulfide prevents FeCl 3-induced carotid artery thrombosis by inhibiting coagulation and activating fibrinolysis .