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[血栓通注射液对大鼠血栓形成及血流的影响]

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

作者信息

Liu Lei, Ding Shi-Lan, Chen Ying, Zhang Qiong-Ling, Zhang Qian, Sun Zheng-Xiao, Liao Fu-Long, You Yun

机构信息

Institude of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.

Guangxi Wuzhou Pharmaceutical (Group) Co., Ltd. Wuzhou 543002, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2020 May;45(10):2446-2453. doi: 10.19540/j.cnki.cjcmm.20191112.404.

DOI:10.19540/j.cnki.cjcmm.20191112.404
PMID:32495605
Abstract

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.

摘要

本文旨在从血流、血管内皮和血小板之间的相互作用方面,探讨血栓通注射液(冻干粉末,XST)对κ-卡拉胶诱导的血栓形成和血流的影响。将50只雄性Sprague-Dawley大鼠(190 - 200 g)随机分为五组:对照组、模型组、肝素钠(1000 U·kg⁻¹)组、低剂量和高剂量(50、150 mg·kg⁻¹)XST组。大鼠腹腔注射相应药物和生理盐水(正常对照组和模型组),持续10天。在第7天腹腔注射药物1小时后,每只大鼠经尾静脉注射溶解于生理盐水中的κ-卡拉胶(Ⅰ型,1 mg·kg⁻¹),以建立尾血栓模型。在建模后2、6、24和48小时测量大鼠黑尾的长度。使用Vevo®2100小动物超声成像系统检测大鼠颈总动脉内径、血流速度和心率,然后计算血流量和剪切率。同时,用激光散斑血流成像系统检测大鼠大腿表面和尾部的微循环血流灌注。采用血小板聚集测定法检测大鼠最大血小板聚集率。通过苏木精-伊红染色观察尾部病理变化,并用蛋白质免疫印迹法检测血小板压电蛋白1的蛋白质含量。结果显示:XST可抑制大鼠尾部动脉血栓形成,并显著缩短黑尾长度(P<0.05)。XST低剂量组颈总动脉血流量显著高于模型组(P<0.05)。与模型组相比,XST高剂量组可显著增加大鼠尾部的微循环血流灌注(P<0.05)。XST高剂量组可显著抑制血小板聚集率(P<0.05),XST低剂量组可显著抑制血小板压电蛋白1的蛋白表达(P<0.01)。综上所述,XST对大鼠κ-卡拉胶诱导的血栓形成具有防治作用,可能与其显著抑制血小板聚集、改善机体血流状态、维持正常血流动力学环境及影响机械离子通道蛋白压电蛋白1有关。

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引用本文的文献

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Proteomic analysis revealed the pharmacological mechanism of Xueshuantong injection in preventing early acute myocardial infarction injury.蛋白质组学分析揭示了血栓通注射液预防早期急性心肌梗死损伤的药理机制。
Front Pharmacol. 2022 Dec 21;13:1010079. doi: 10.3389/fphar.2022.1010079. eCollection 2022.
2
Xueshuantong Injection in Treating Deep Venous Thrombosis: A Systematic Review and Trial Sequential Analysis.血栓通注射液治疗下肢深静脉血栓形成的系统评价与累积Meta分析
Evid Based Complement Alternat Med. 2021 Apr 7;2021:6622925. doi: 10.1155/2021/6622925. eCollection 2021.
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Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca Signaling Pathway.
血栓通通过靶向Piezo1通道介导的钙信号通路抑制剪切诱导的血小板聚集
Front Pharmacol. 2021 Mar 22;12:606245. doi: 10.3389/fphar.2021.606245. eCollection 2021.
4
Efficacy and safety of high-dose Xueshuantong injection (lyophilised) in reducing the incidence of major adverse cardiovascular events in patients with unstable angina: a protocol of a randomised, parallel-arm, controlled, double-blind and multicentre clinical trial based on dual antiplatelet therapy.大剂量注射用血栓通(冻干)降低不稳定型心绞痛患者主要不良心血管事件发生率的有效性和安全性:一项基于双联抗血小板治疗的随机、平行对照、双盲、多中心临床试验方案
BMJ Open. 2020 Aug 26;10(8):e038074. doi: 10.1136/bmjopen-2020-038074.