莪术油明胶微球制剂急性毒性实验

Experimental Study of the Acute Toxicity of the Zedoary Turmeric Oil Gelatin Microsphere

目的 :研究莪术油明胶微球 (ZT GMS)制剂的急性毒性 ,探讨该制剂作介入用药的安全性。方法 :74只大鼠分成 7组 ,行胃十二指肠动脉插管至肝固有动脉 ,模拟介入给药方法 ,分别一次性注入 0 .3 %羧甲基纤维素钠 3 .5mL·kg 1 、莪术油 3 .2mg·kg 1 、明胶微球 40mg·kg 1 及ZT GMS 5 .0 ,10 .0 ,2 0 .0 ,40 .0mg·kg 1 ,连续观察给药后大鼠的急性毒性表现 ,共 14d ,并检测血液生化指标 ,用Bliss法计算LD50 。结果 :ZT GMS肝动脉给药的LD50 为 17.19mg·kg 1 ;死亡大鼠丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素、直接胆红素、血肌酐及尿素氮均明显升高 ,而存活大鼠各组间血生化指标未见有显著变化 ;病理组织学检查则表明有异位栓塞的可能。结论 :ZT GMS的急性毒性可能源于微球本身的异位栓塞 ,而与微球所包含的莪术油关系不大。

Objective:In order to observe the safety of a special preparation form zedoary turmeric oil gelatin microspheres (ZT GMS) for interventional therapy, we studied the acute toxicity of ZT GMS. Methods:ZT MGS was administered through the proper hepatic artery, the manifestations of acute toxicity was observed for 14 days, the biochemical indices of blood tested, and the LD 50 calculated with Bliss method. Results:The LD 50 of ZT GMS administered via proper hepatic artery was 17.19 mg·kg 1 , the GPT?GOT?T BiL?D BiL?BCr and BUN of the dead animals were significantly increased, while changes of the biochemical indices in the survived animals were not significant. The results of the histopathological examination suggested the possibility of dystopic embolism occurrence in animals administered with ZT GMS. Conclusion:The study indicated that the acute toxicity of ZT GMS might result from the dystopic embolism rather than the oil of zedoary turmeric itself entrapped in ZT GMS.