注射用血栓通抑制血栓形成及其对血流状态影响的研究

从血流/血管/血液相互作用的角度,研究血栓通注射液(冻干粉,XST)对角叉菜胶诱导的血栓形成及血流状态的影响。将50只雄性SD大鼠(190~200 g)随机分为5组,即正常组,模型组,血栓通低、高剂量组(50,150 mg·kg^-1),阳性对照肝素钠组(1 000 U·kg^-1),腹腔注射连续给药10 d,正常及模型组给予等体积生理盐水;在第7天给药1 h后尾静脉注射1 mg·kg^-1角叉菜胶建立大鼠尾部血栓模型;造模后2,6,24,48 h测量大鼠黑尾长度;以Vevo■2100小动物超声成像系统检测大鼠颈总动脉血管内径、血流速度、心率等指标并计算血流量及血流剪切率;以激光散斑血流成像系统检测大鼠股、尾部微循环血流灌注量;以血小板聚集仪检测血小板最大聚集率;HE染色法观察尾部病理学变化;Western blot法检测血小板piezo1蛋白含量。结果显示,XST可抑制角叉菜胶诱导的大鼠鼠尾动脉血栓形成,明显缩短黑尾长度(P<0.05);与模型组相比,XST低剂量组可明显增高大鼠颈总动脉血流量(P<0.05);XST高剂量组可明显改善大鼠尾部微循环血流灌注量(P<0.05);XST高剂量组可明显抑制血小板聚集率(P<0.05);XST低剂量组可明显抑制血小板piezo1蛋白表达(P<0.01)。综上,对于角叉菜胶诱导的大鼠血栓模型,XST发挥抗血栓的效果,可能与其明显抑制血小板聚集,改善机体血流状态,维持血流正常力学环境进而作用于机械力离子通道蛋白piezo1有关。

Effects of Xueshuantong Injection on thrombosis formation and blood flow in rats

The aim of this paper was to explore the effect of Xueshuantong Injection(freeze-dried powder,XST) on κ-carrageenan-induced thrombosis and blood flow from the aspects of interactions among blood flow,vascular endothelium and platelets. Fifty male Sprague-Dawley rats(190-200 g) were randomized into five groups: control group, model group, heparin sodium(1 000 U·kg-1) group, low-dose and high-dose(50, 150 mg·kg^-1) XST groups. Rats were intraperitoneally injected with corresponding drugs and normal saline(normal control and model groups) for 10 days. One hour after drugs were administered intraperitoneally on the 7 th day, each rat was injected with κ-carrageenan(Type Ⅰ, 1 mg·kg^-1) which was dissolved in physiological saline by intravenous administration in the tail to establish tail thrombus model. The lengths of black tails of the rats were measured at 2, 6, 24 and 48 h after modeling. Vevo?2100 small animal ultrasound imaging system was used to detect the internal diameter of rat common carotid artery, blood flow velocity and heart rate, and then the blood flow and shear rate were calculated. Meanwhile, the microcirculatory blood flow perfusion in the thigh surface and tail of rats were detected by laser speckle blood flow imaging system. Platelet aggregometry was used to detect the max platelet aggregation rate in rats. Pathological changes in tail were observed through hematoxylin-eosin staining, and Western blot was used to detect the protein content of platelet piezo1. According to the results, XST could inhibit the rat tail arterial thrombosis and significantly reduce the length of black tail(P<0.05). The blood flow of common carotid artery in XST low dose group was significantly higher than that in the model group(P<0.05). XST high dose group could significantly increase the microcirculatory blood flow perfusion of the tail in rats as compared with the model group(P<0.05). XST high dose group could significantly inhibit platelet aggregation rate(P<0.05) and XST low dose group could significantly inhibit platelet piezo1 protein expression(P<0.01). In summary, XST could play an effect in fighting against thrombosis induced by κ-carrageenan in rats, which may be related to significantly inhibiting platelet aggregation, improving body′s blood flow state, maintaining normal hemodynamic environment and affecting mechanical ion channel protein piezo1.