精制蛇毒酶的毒理学研究

摘要目的观察精制蛇毒酶的安全性。方法小鼠100只，随机分成两组，尾静脉注射或腹腔注射精制蛇毒酶后观察动物出现的急性毒性反应，计算半数致死量（LD50）。小鼠120只，随机分为4组，各30只；家兔40只，随机分成4组。观察不同剂量组小鼠连续腹腔给药90 d，家兔静脉给药45 d（隔天一次）的健康状况。在给药后第91天采血，检测丙氨酸氨基转移酶、尿素氮和血常规，并对肝肾组织作病理学检查。结果精制蛇毒酶小鼠尾静脉给药的半数致死量（ivLD50）为6.695 U•kg－1，90%的可信限为5.434～7.956 U•kg－1；小鼠腹腔给药的半数致死量（ipLD50）为4.599 U•kg－1，90%的可信限为3.735～5.462 U•kg－1；各剂量小鼠和家兔肝、肾功能及血常规指标与空白组比较均差异无统计学意义（均 P＞0.05），病理组织学检查未见明显异常。结论在实验剂量范围内，精制蛇毒酶属低毒性。乳膏中蛇毒酶的含量为1.25×10－2 U•g－1，按成人用量0.05 g•cm－1（6.25×10－4 U•cm－1酶活力）局部用药，其用量安全可靠。

Toxicological Study of Purified Snake Venom Enzyme

Objective To evaluate the safety of purified snake venom enzyme(PSE).Methods One hundred mice were randomly divided into two groups for the median lethal dose(ivLD50 and ipLD50) test through tail vein injection and intraperitoneal injection,respectively.A total of 120 mice and 40 rabbits were randomly divided into four groups for the effects study of the tested groups at different doses.The mice were administered PSE for 90 days continuously and rabbits were treated with PSE for 45 days(every other day).On the 91st day,blood was collected and ALT,BUN and routine blood testing were carried out.The liver and kidney tissues were moved for pathological examination.Results The ivLD50 of PSE was 6.695 U·kg-1,90% confidence interval was 5.434-7.956 U·kg-1;ip LD50 of PSE was 4.599 U·kg-1,90% confidence interval was 3.735-5.462 U·kg-1.Compared with that of the control group,no significant difference(P>0.05) was showed on the function of liver and kidney and blood indicators.Conclusion PSE has low toxicity at the experimental doses.Since the amount of enzyme is 1.25×10-2 U·g-1 in cream,the dosage for adults(0.05 g·cm-1 equivalent to 6.25×10-4 U·cm-1 enzyme activity) is safe and reliable.