摘要
目的研究去铁胺对血小板功能和实验性血栓形成的影响。方法采用血小板聚集仪检测去铁胺对血小板聚集的影响;采用免疫荧光法检测去铁胺对血小板在胶原上黏附功能的影响;采用ELISA试剂盒检测去铁胺对血小板超氧化物歧化酶活性和丙二醛含量的影响。将C57BL/6小鼠随机分为模型组和低、高剂量(50、100 mg·kg^(-1))去铁胺组,去铁胺组进行预处理给药,腹腔注射给药7 d,模型组给予等体积的生理盐水。给药7 d后,构建氯化铁诱导的动脉血栓模型,采用活体显微镜检测首次形成血栓的时间和形成闭塞性血栓的时间,检测动脉血栓的重量和长度,同时通过免疫组化切片分析动脉血栓形态。构建下腔静脉血栓模型,检测静脉血栓的重量和长度。结果去铁胺可显著抑制血小板聚集,降低血小板在胶原上的黏附,改善血小板的氧化应激,延长动脉血栓形成时间,降低动脉血栓的重量和长度,降低动脉血栓中血小板的致密程度及降低静脉血栓的重量和长度。结论去铁胺可抑制血小板活化和实验性动脉血栓形成。
OBJECTIVE To study the effects of deferoxamine on platelet function and experimental thrombus formation.METHODS The effect of deferoxamine on platelet aggregation was measured by using platelet aggregometer.The effect of deferoxamine on platelet adhesion to monomeric collagen was detected by immunofluorescence.The effect of deferoxamine on platelet superoxide dismutase and malondialdehyde level was detected by ELISA assay kit.Then C57 BL/6 mice were equally divided into the model groups,low dose and high dose(50,100 mg·kg^(-1))of deferoxamine groups.The deferoxamine group was intraperitoneally administration with deferoxamine for 7 days.The model groups were given to the same volume of normal saline.After administration for 7 days,the model of Fe Cl3-induced carotid artery thrombosis was constructed,and then the time to form the first thrombus and form occlusive thrombus was assessed by intravital microscopy,the weight and length of arterial thrombus was measured,and the morphological change of arterial thrombus was analyzed by immunohistochemical analysis.The model of inferior vena cava thrombus was constructed,and the weight and length of venous thrombus were measured.RESULTS Deferoxamine could significantly suppress platelet aggregation,inhibit adhesion of platelets to collagen,improve platelet oxidative stress,prolong thrombus formation time,reduce the weight and length of arterial thrombus,reduce the compactness of platelet in arterial thrombosis,and reduce the weight and length of venous thrombus.CONCLUSION Deferoxamine inhibits platelet activation and experimental thrombus formation.
作者
明月
李世一
辛光
钮海
邢志华
黄文
MING Yue;LI Shiyi;XIN Guang;NIU Hai;XING Zhihua;HUANG Wen(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China;West China Hospital,Sichuan University,Chengdu,Sichuan,610041 P.R.China)
出处
《华西药学杂志》
CAS
CSCD
2021年第2期188-192,共5页
West China Journal of Pharmaceutical Sciences
基金
国家自然科学基金资助项目(批准号:81803866,81673710,81973580)
新药创制国家科技重大专项(批准号:2019ZX09201005-005-001,2019ZX09201005-005-004)。
关键词
去铁胺
血小板聚集
血小板黏附
超氧化物歧化酶
丙二醛
动脉血栓
静脉血栓
体内外评价
Deferoxamine
Platelet aggregation
Platelet adhesion
Superoxide dismutase
Malondialdehyde
Arterial thrombosis
Venous thrombosis
In vivo and in vitro evaluation