白眉蝮蛇毒精氨酸酯酶的长期毒性实验

研究白眉蝮蛇 (Agkistrodon halys ussuriensis)毒中精氨酸酯酶的长期毒性 ,为临床应用提供依据。用Beagle犬进行长期毒性实验 ,将犬分成 4组 ,每组 4只 ,对照组 (生理盐水 )、精氨酸酯酶低剂量组 (0 .0 6 u/ kg)、中剂量组 (0 .18u/ kg)和高剂量组 (0 .36 u/ kg)。静脉给药每天 1次 ,每周 6 d,连续给药 180 d后每组处死 3只 ,留 1只停药饲养 15 d。观察用药期间毒性反应及停药 15 d期间恢复情况。通过对活动能力、生长率、进食量、死亡率等一般综合指标 ;血检、尿检等临床指标 ;病理解剖和脏器系数变化几方面对毒性反应进行分析评价。一般综合指标 ,药物处理组和对照组没有明显差别 ;临床指标 ,高剂量药物处理组肝功能与对照组相比有明显差异 ,其它生化指标无显著差异 (P>0 .0 5 ) ;病理解剖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对照组 (P<0 .0 5 ) ,但停药后肝脏恢复正常 ,其它脏器未见病变 ,脏器系数无显著差异 (P>0 .0 5 )。纯精氨酸酯酶对犬的无毒反应剂量大约为 0 .18u/ kg。从长期毒性方面考虑 ,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 ,在高于临床治疗剂量约 15倍的条件下长期用药仍然安全

Long-term Toxicity Test of Arginine Esterase from Agkistrodon Halys Ussuriensis Venom

To study the long-term toxicity of arginine esterase from Agkistrodon halys ussuriensis venom for the clinical application of arginine esterase in the future. Beagle dogs were used as experimental animals and were divided into control group, arginine esterase low dose group (0.06 u/kg), the middle dose group (0.18 u/kg) and high dose group (0.36 u/kg). Every group consisted of four dogs. The arginine esterase was given intravenously once a day for 180 days. Then three dogs in each group were sacrificed and the fourth one was fed without injecting arginine esterase for 15 days. The toxic reactions during treatment and recovery period were determined by evaluating and comparing the general criteria ( including locomotor activity, growth rate, appetite and death rate), clinical criteria (including blood test and urine test), pathological dissection and viscera coefficient of the treated animals and the control animals. There were no significant differences in general criteria. The clinical criteria of the treated animals were the same as those of the control animals except liver function. There were no significant differences in pathological dissection and viscera coefficient between the treated animals and the control animals except livers. The livers in high dose arginine esterase treated animals were swollen and vacuolated and there was significant difference in liver coefficient between them (P<0.05). The toxic symptom of liver disappeared after withdrawal of treatment. From these results, the non-toxic dose of arginine esterase for dogs was estimated to be 0.18 u/kg under the present study conditions and is about 15 times the clinical dosage for using the drug "Qingshuanmei" of which the main component is arginine esterase. The long-term toxicity test result indicates that the toxicity of pure arginine esterase is lower than that of "Qingshuanmei", suggesting that clinical use of the arginine esterase is safe.