鸦胆子油自微乳化颗粒对大鼠长期毒性实验

Long-term Toxicity of Self-microemulsifying Granules of Brucea Javanica Oil on Rat

目的考察鸦胆子油自微乳化颗粒对大鼠的长期毒性。方法将120只斯泼累格·多雷(SD)大鼠随机分为空白对照组、鸦胆子油自微乳化颗粒大剂量组、中剂量组、小剂量组,每组30只。鸦胆子油自微乳化颗粒大、中、小剂量组分别按照144,72,36倍人体服用剂量给药,并同时进行空白对照。于给药前、给药3,6个月及停药后4周进行大鼠体质量、血液学、血液生化学、脏器指数、病理组织学检查。结果一般观察指标及体质量均未见显著变化:血液学指标:3个月时与空白对照组比较,大剂量组淋巴细胞比率(LY)降低、单核细胞比率(MO)升高,中剂量组MO、嗜碱性细胞比率(BA)均显著升高(P<0.01),给药6个月后与空白对照组比较,大剂量组红细胞容积(HCT)比率降低、中剂量组中性粒细胞计数(NE)升高(P<0.01);停药4周后,以上项目均恢复,与空白对照组比较,差异无统计学意义(P>0.05)。血液生化学指标:3个月时与空白对照组比较,大剂量组总蛋白(TP)、球蛋白(G)、丙氨酸氨基转移酶(ALT),中剂量组TP均升高(P<0.05),大剂量组天冬氨酸氨基转移酶(AST)显著升高(P<0.01);给药6个月后大剂量组AST升高、三酰甘油(TG)降低(P<0.05),中剂量组肌酸激酶(CK)降低(P<0.05)、TG显著降低(P<0.01),小剂量组葡萄糖(Glu)显著降低(P<0.01);停药4周后,以上指标均可恢复。尸解及脏器指数:停药后大鼠出现肝脏、睾丸迟发型肿大,整个实验过程未出现动物死亡;病理组织检查未见显著变化。结论鸦胆子油自微乳化颗粒长期服用毒性较低,可进一步进行深入研究。

Objective To test long-term toxicity of self-microemulsifying granules of Brucea javanica oil on SD rats.Methods The SD rats were divided into blank control group,high-,medium- and low-dose（ 144,72 and 36 folds of dosage for human,respectively） of self-microemulsifying granules of Brucea javanica oil groups randomly（ n = 30 each group）.The weight,appetite,haematological indexes,blood biochemical indexes,visceral index and histopathologic changes of organs of rats were measured at time point after 3,6 months treatment and 4 weeks after drug withdrawal,respectively. Results Compared with blank control group,the drug groups showed no significant differences in the appearance and weight of rats. With haematological indexes,the level of lymphocyte rate（ LY） in high dose group was lower while the levels of monor（ MO） in high dose group was higher,MO and basic cells rate（ BA） in medium dose group were significantly higher than those in blank control group（ P〈0.01）after 3-month long treatment.Hematocrit（ HCT） in high dose group was lower,neut（ NE） in medium dose group was higher than those in blank control group（ P〈0.01） after 6-month long treatment.Those changed indexes recovered to be blank on the 4th week after withdrawal. No significant difference was obtained compared with blank control group（ P〈0. 05）. In blood biochemical indexes,the levels of total protein（ TP）,albumin（ G）,glutamic-pyruvic transaminase（ ALT） in high dose group and TP in medium dose group were higher than those in blank control group（ P〈0. 05）. Glutamic-oxalacetic transaminase（ AST） in high dose group was significantly higher than that in blank control group（ P〈0. 01） after 3 months. After 6 months treatment,compared with blank control group,the level of glutamic-oxalacetic transaminase（ AST） in high dose group was higher while trilaurate glycerin（ TG） was lower（ P〈0.05）. The level of creatine kinase（ CK） was lower（ P〈0. 05） and the level of TG was significantly lower（ P〈0.01）.The level of glucose（ Glu） was significantly lower（ P〈0.01）. Those changed indexes recovered to be blank on the 4th week after withdrawal. In haematological indexes,delayed enlargements of liver and testis occurred after withdrawal.No rat died in the process of experiment. No obvious histopathologic changes of organs of rats were observed.Conclusion Self-microemulsifying granules of Brucea javanica oil have no apparent toxicity.It is worthy of further research.