白眉蝮蛇毒精氨酸酯酶的急性、亚急性毒性实验

ACUTE AND CHRONIC TOXICITY TESTS OF ARGININE ESTERASE FROM AGKISTRODON HALYS USSURIENSIS VENOM

用小鼠和大鼠分别研究了白眉蝮蛇 (Agkistrodonhalysussuriensis )蛇毒中精氨酸酯酶的急性毒性和亚急性毒性 .腹腔和静脉给药小鼠急性毒性分别为 :半数致死量LD50 ,ip=5 .73～ 6 .6 8U/kg ,LD50 ,iv=4 .12～ 4 .76U/kg ;最大致死量LD10 0 ,ip=8.6 0U/kg ,LD10 0 ,iv=6 .4 0U/kg ;最小致死量LDmin ,ip=4 .2 0U/kg,LDmin,iv=3.10U/kg .大鼠急性毒性结果分别为 :LD50 ,ip=5 .0 9～ 5 .98U/kg ,LD50 ,iv=3.30～ 3.86U/kg ;LD10 0 ,ip=7.80U/kg ,LD10 0 ,iv=5 .5 0U/kg ;LDmin ,ip=3.6 0U/kg ,LDmin ,iv=2 .70U/kg .大鼠亚急性毒性实验结果为 :活动能力、生长率、进食量、死亡率等一般综合指标药物处理组和CK没有明显差别 ;血检、尿检等临床指标除谷丙转氨酶 (GPT)高剂量药物处理组与CK有明显差异外 (P <0 .0 5 ) ,其它生化指标无显著差异 (P >0 .0 5 ) ;病理解剖和脏器系数指标 ,高剂量药物处理组肝脏明显肿大、空泡化 ,脏器系数也明显高于CK(P <0 .0 5 ) ,其它脏器未见病变 ,脏器系数未见显著差异 (P >0 .0 5 ) .从急性毒性和亚急性毒性方面考虑 ,纯精氨酸酯酶比现在临床应用的“蝮蛇清栓酶”(主要成分为精氨酸酯酶 )毒性低 .表 3参

The acute and chronic toxicities of arginine esterase from Agkistrodon halys ussuriensis venom were studied using mice and Wistar rats. The LD 50 , LD 100 , and LD min using mice as experimental animals were LD 50,ip =5.73～6.68 U/kg, LD 50,iv =4.12～4.76 U/kg;LD 100,ip =8.60 U/kg, LD 100,iv =6.40 U/kg;LD min,ip =4.20 U/kg, LD min,iv =3.10 U/kg. The LD 50 , LD 100 and LD min using Wistar rats as experimental animals were LD 50,ip = 5.09～5.98 U/kg, LD 50,iv =3.30～3.86 U/kg ; LD 100,ip =7.80 U/kg, LD 100,iv =5.50 U/kg; LD min,ip =3.60 U/kg, LD min,iv =2.70 U/kg. Chronic toxicity tests were conducted using Wistar rats. There were no significant differences in comprehensive standards (including locomortor activity, growth rate, appetite and death rate) between the arginine esterase treated animals and the control animals. For clinical standards (including blood test and urine test), the treated animals were the same as the control animals except GPT (P<0.05). There were no significant differences in pathological dissection between the treated animals and the control animals except livers which swelled and vacated in high dose arginine esterase treated animals and there was significant difference in liver coefficient between the high dose treated animals and the control animals (P<0.05). From the result it can be concluded that the acute toxicity and chronic toxicity of the pure arginine esterase to mice and rats are lower than the drug 'Qingshuanmei' whose main component is arginie esterase. Tab 3, Ref 11