前列地尔对模型大鼠深静脉血栓的改善作用

Positive Effect of Alprostadil on Deep Venous Thrombosis in Rats

目的探讨前列地尔对模型大鼠深静脉血栓的改善作用。方法将60只SD大鼠随机分为假手术组(等体积生理盐水灌胃)、模型组(等体积生理盐水灌胃)、低分子肝素钠组(360 IU/kg皮下注射)及前列地尔低、中、高剂量组(2.5,5.0,10.0μg/kg腹腔注射),各10只。采用结扎下腔静脉法复制深静脉血栓大鼠模型,假手术组仅开腹腔。建模成功后,各组大鼠给予相应药物或生理盐水,每日1次,连续14 d。测定大鼠静脉血活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、D-二聚体(D-D)水平;采用酶联免疫吸附(ELISA)法测定血浆血栓素B_(2)(TXB_(2))、组织纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物-1(PAI-1)水平;采用苏木素-伊红(HE)染色,显微镜下观察血管组织病理形态学;采用实时定量聚合酶链反应(RT-qPCR)法及Westernblot法测定血管组织血栓调节蛋白(TM)、血管细胞黏附分子-1(VCAM-1)、组织因子(TF)mRNA及蛋白的表达水平。结果与模型组比较,各用药组大鼠的APTT,PT,TT均显著延长(P<0.05),t-PA水平及TM的mRNA和蛋白表达水平均显著升高(P<0.05),D-D,TXB_(2),PAI-1水平及VCAM-1和TF的mRNA和蛋白表达水平均显著降低(P<0.05)。模型组大鼠静脉血管血栓可见形成及血管内皮炎性浸润;各用药组大鼠与之比较,静脉血管血栓形成减少,血管内皮炎性浸润程度减轻。结论前列地尔能抑制模型大鼠深静脉血栓的形成,其机制可能与改善凝血功能和修复深静脉血管内皮损伤有关。

Objective To investigate the positive effect of alprostadil on deep venous thrombosisrats in rats.Methods Sixty SD rats were randomly divided into the sham operation group(gavaged with equal volume of normal saline),model group(gavaged with equal volume of normal saline),low molecular weight heparin sodium group(subcutaneously injected with 360 IU/kg of heparin sodium),and alprostadil low-,middle-and high-dose groups(intraperitoneally injected with 2.5,5.0,10.0μg/kg of alprostadil),with ten rats in each group.The inferior vena cava(IVC)was ligated to replicate the deep venous thrombosis rat model,while the sham operation group were only opened the abdominal cavity.After successful modeling,the rats were treated with corresponding drugs or normal saline once a day for 14 days.The activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT)and D-dimer(D-D)of rats were determined.The levels of plasma thromboxane B_(2)(TXB_(2)),tissue plasminogen activator(t-PA)and plasminogen activator inhibitor-1(PAI-1)of rats were detected by enzyme-linked immunosorbent assay(ELISA).The morphopathology of vascular tissue of rats were observed by hematoxylin-eosin(HE)staining using microscope.The expression levels of vascular tissue thrombomodulin(TM),vascular cell adhesion molecule-1(VCAM-1)and tissue factor(TF)mRNA and protein were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and western blot.Results Compared with those in the model group,APTT,PT and TT extended significantly,the level of t-PA,the expression levels of TM mRNA and protein increased significantly(P<0.05),while the levels of D-D,TXB_(2)and PAI-1 and the expression levels of VCAM-1,TF mRNA and protein decreased significantly in other groups with corresponding drugs(P<0.05).The venous thrombosis of model group was formed with vascular endothelial inflammatory infiltration.Compared with model group,the formation of venous thrombosis of rats in other groups with corresponding drugs decreased,while the degree of vascular endothelial inflammatory infiltration were lightened.Conclusion Alprostadil can depress the formation of deep vein thrombosis in rats,the mechanism of which could be related with the improvement of coagulation function and the repairment of deep venous endothelium injury.