眼镜王蛇毒中酸性磷脂酶A_2对三氯化铁诱导的大鼠动脉血栓形成的抑制作用  

Inhibition of acidic phospholipase A_2 from Ophiophagus hannah venom on arterial thrombosis induced by FeCl_3 in rat

作　　者：张维文[1] 张贵平[1] 罗健东[1] 钟蓓华[1] 区慧坚[1] 

机构地区：[1]广州医学院药理学教研室,广东广州510182

出　　处：《中国药理学与毒理学杂志》2004年第1期37-41,共5页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的　研究眼镜王蛇毒中酸性磷脂酶A2 组分Ⅰ (命名为APLA2 Ⅰ)抑制动脉血栓形成的能力 ,观察将其开发成抗血栓药物的可能性。方法　模型组大鼠舌下ivPBS,3组APLA2 Ⅰ预治疗组大鼠分别舌下ivAPLA2 Ⅰ 1 .0 ,0 .5和 0 .1mg·kg-1 。各组给药 30min后 ,用 40 %FeCl3 诱导大鼠腹主动脉血栓形成 ,监测远端腹主动脉压 ,记录最低腹主动脉压和血栓形成时间 ,测量血栓面积及血栓重量。采用大鼠体外血浆凝块回缩实验观察APLA2 Ⅰ对血浆凝块回缩的影响。用小鼠尾动脉出血实验观察APLA2 Ⅰ对出血时间的影响。结果　预ivAPLA2 Ⅰ 1 .0 ,0 .5及 0 .1mg·kg-1 可抑制FeCl3 诱导的大鼠血栓形成后的腹主动脉压下降 ,使最低腹主动脉压从(4.0± 0 .5)kPa(模型组 )分别增高至 (7.7± 1 .0 ) ,(6 .8±0 .8)和 (5 .4± 0 .7)kPa ;使血栓形成时间从(31±4)min(模型组 )分别延长至 (60± 7) ,(53± 5)和(49± 6)min;使血栓面积从 (1 0 62± 1 39) μm2 (模型组 )分别减少至 (72 4± 74) ,(785± 96)和 (91 0±1 2 6) μm2 ;使 0 .5cm长血管内血栓重量从 (5 .2±0 .6)mg(模型组 )分别减少至 (3 .5± 0 .5) ,(3 .8±0 .5)和 (4.6± 0 .6)mg(P <0 .0 5 ,n =1 0 )。体外实验显示APLA2 Ⅰ能剂量依赖性地抑制大鼠血浆凝块回缩?AIM To study whether APLA 2 Ⅰ is a candidate of antithrombotic drug. METHODS Model group rats were pretreated with iv(sublingual) PBS, three dose group of APLA 2 Ⅰ pretreated rats were pretreated with iv(sublingual) APLA 2 Ⅰ 1.0, 0.5, 0.1 mg·kg -1 for 30 min, respectively. Then the abdominal aortic thrombosis of rats induced by 40% FeCl 3 . The distal abdominal aortic pressure(AAP) of rats was monitored continually to take lowest AAP and thrombosis time. Thrombus area and thrombus weight were measured. Effect of APLA 2 Ⅰ on plasma clot retraction was investigated by the method of rat blood plasma clot retraction in vitro . Effect of APLA 2 Ⅰ on hemorrhage time was investigated by the method of mouse cauda arterial hemorrhage. RESULTS Pretreatment with iv APLA 2 Ⅰ 1.0, 0.5 , 0.1 mg·kg -1 can inhibit the dropping of distal AAP due to the thrombosis induced by FeCl 3, the lowest AAP was raised from (4.0±0.5) kPa (model group) to (7.7±1.0), (6.8± 0.8) , (5.4±0.7)kPa, respectively; the thrombosis time was extended from (31±4) min (model group) to (60±7), (53±5), (49±6)min, respectively; the thrombus area was reduced from (1062±139)μm 2 (model group) to (724±74), (785±96), (910±126)μm 2, respectively; the thrombus weight in 0.5 cm blood vessel section was decreased from (5.2±0.6)mg (model group) to (3.5±0.5), (3.8±0.5), (4.6± 0.6)mg , respectively. In vitro APLA 2 Ⅰ can inhibit the rat plasma clot retraction dose dependently. When mice were pretreated with ip APLA 2 Ⅰ 1.0, 0.5, 0.1 mg·kg -1 for 1 h, the caudal arterial hemorrhage time was prolonged from (1.4±0.4)min (control group ip PBS) to >10 , >10, (7.5±1.8)min, respectively. CONCULUSION APLA 2 Ⅰ can inhibit arterial thrombosis induced by FeCl 3 in rats.

关 键 词：蛇毒液类 酸性磷脂酶A2 眼镜王蛇毒 三氯化铁 动脉血栓形成 抑制作用 

分 类 号：R96[医药卫生—药理学]