蛇毒血小板抑制因子对心肌缺血再灌注损伤大鼠血小板膜糖蛋白Ⅵ表达以及血液流变的影响及意义  

Agkistrodon halys venom platelet inhibitor inhibits GPⅥ expression and changes hemorheology in rats with acute myocardial ischemia reperfusion injury

作　　者：吴娟[1] 张鹤 冯桂林 WU Juan;ZHANG He;FENG Guilin(Department of Pathophysiology,Wannan Medical College,Wuhu 241000,Anhui,China;Department of Respiratory Medcine,Yijishan Hospital of Wannan Medical College,Wuhu 241000,Anhui,China;Department of Vascular Surgery,Yijishan Hospital of Wannan Medical College,Wuhu 241000,Anhui,China)

机构地区：[1]皖南医学院病理生理教研室,安徽芜湖241000 [2]皖南医学院第一附属医院弋矶山医院呼吸内科,安徽芜湖241000 [3]皖南医学院第一附属医院弋矶山医院血管外科,安徽芜湖241000

出　　处：《中国临床药理学与治疗学》2020年第1期49-54,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：2018年安徽省高校自然科学研究项目(KJ2018A0269)

摘　　要：目的:探讨皖南蝮蛇毒血小板抑制因子(agkistrodon halys venom platelet inhibitor,AHV-PI)对心肌缺血再灌注损伤(myocardial ischemia reperfusion injury,MIRI)、大鼠血小板膜糖蛋白VI(GPVI)表达以及血液流变的影响及意义。方法:SD雄性大鼠30只,随机分为假手术组(6只)、心肌缺血再灌注损伤模型组(6只)和AHV-PI实验组(18只),实验采用结扎大鼠左冠状动脉前降支方法制备大鼠MIRI模型。AHV-PI实验组根据大鼠舌下静脉注射AHV-PI的剂量(0.05,0.1,0.2 mg/kg)再依次分为低、中、高三组,每组6只,RM6240生物信号采集处理系统监测心电变化。蛋白质免疫印迹法(Western blot)监测AHV-PI干预下,大鼠GPVI的表达水平。血栓弹力仪(TEG■5000)描记凝血时间(R)、血凝块形成时间(K)、Alpha角度(A)和凝血最大幅度(MA)。采用比浊法检测血小板聚集率。结果:与MIRI模型组相比,AHV-PI中剂量实验组和高剂量实验组GPVI表达水平明显降低(P<0.05);R值和K值明显延长,A值和MA值减小(P<0.05);血小板聚集时间、聚集幅度和聚集率均明显降低(P<0.05)。结论:AHV-PI可显著抑制MIRI大鼠GPVI的表达并可改善大鼠心肌损伤相关的血液流变学特性,进而弱化其损伤过程。AIM:To explore effect and meaning of Agkistrodon halys venom platelet inhibitor on GPVI expression and hemorheology in rats with acute myocardial ischemia reperfusion injury. METHODS:Thirty matched SD male rats were randomly divided into sham operation group(6 rats), myocardial ischemia-reperfusion injury(MIRI) model group(6 rats) and agkistrodon halys venom platelet inhibitor(AHV-PI) group(18 rats). The AHV-PI experimental group was divided into low, middle and high dose groups according to the dose of AHV-PI injected into sublingual vein(0.05, 0.1, 0.2 mg/kg), with 6 rats in each group. Electrocardiogram(ECG) changes of rats were monitored by RM6240 biological signal collection and processing system. Western blot was used to monitor the expression of platelet membrane glycoprotein VI(GPVI) in rats under the intervention of AHV-PI. Blood coagulation time(R), blood clots forming time(K), Alpha Angle(A), and maximum amplitude of blood coagulation(MA) were assayed by Thrombelastography(TEG■5000).Platelet aggregation rate was measured by turbidimetry. RESULTS:Compared with MIRI model group, the expression level of GPVI AHV-PI medium dose experimental group and high dose experimental group were significantly decreased(P<0.05), and the R and K values were significantly prolonged, while the A value and MA values were significantly decreased(P<0.05). Platelet aggregation time, aggregation amplitude and aggregation rate were significantly decreased(P<0.05). CONCLUSION: AHV-PI can significantly inhibit the expression of GPVI in MIRI rats and improve the hemorheological properties related to myocardial injury in rats, thus weakening the injury process.

关 键 词：蝮蛇毒血小板抑制因子 心肌缺血再灌注损伤 血液流变 血小板膜糖蛋白Ⅵ 

分 类 号：R965.[医药卫生—药理学]