注射用紫杉肽对比格犬骨髓造血系统的毒性作用研究

Toxicity of paclitaxtide injection on bone marrow hematopoietic system in Beagle Dogs

目的从临床检验及病理学角度研究注射用紫衫肽对比格犬骨髓造血系统的毒性作用。方法 24只比格犬,每组6只,雌雄各半,分为溶剂对照组和紫杉肽注射液3、10和30 mg/kg组;注射用紫杉肽静脉滴注给药,以每21天为1个给药周期,每个周期给药1次,共9个周期。第1、5、9次给药周期后约2、24、72 h取静脉外周血,血液分析仪检测红细胞(RBC)、白细胞(WBC)和淋巴细胞(Lym),并进行血涂片观察;取股骨骨髓,进行涂片分类计数;剖取胸骨切片、HE染色,进行组织病理学检查。结果与溶剂对照组比较,注射用紫杉肽在每次给药2 h后,各剂量组WBC、Lym出现不同程度升高,均呈剂量相关性;24、72 h后呈降低趋势,72 h后30 mg/kg组均显著降低(P<0.05、0.01);RBC在各时间段随着剂量的增加表现出一定的降低趋势,但波动范围较小,差异不显著。涂片结果显示,与溶剂对照组比较,注射用紫杉肽3、10、30mg/kg组骨髓细胞呈稀松散在,出现不同程度造血抑制,30 mg/kg组差异明显;组织学病理检查显示,注射用紫衫肽30 mg/kg组骨髓腔内出现明显造血抑制(P<0.01),而3、10 mg/kg组则造血抑制不明显。结论注射用紫杉肽对比格犬骨髓造血系统具有毒性作用,主要表现为骨髓造血抑制,3、10 mg/kg组呈抑制趋势但差异不显著,30 mg/kg组较明显。

Objective To study the toxicity of paclitaxtide injection on beagle bone marrow hematopoietic system from the perspectives of clinical examination and pathology. Methods Totally 24 beagles were randomly divided into four groups consisting of six animals each： solvent control group and paclitaxtide injection 3, 10 and 30 mg/kg groups, sex in half. The beagles in paclitaxtide injection groups were administered with different concentrations by intravenous drip one cycle per 21 days for 9 cycles, and administered once for every cycle. The peripheral blood of the vein was taken at 2, 24 and 72 h after the first, fifth, ninth cycle. White blood cells（WBC）, red blood cells（RBC） and lymphocytes（Lym） were detected by hematology analyzer. Bone marrow smears were made for counting and classification. Sternum marrow were observed by histopathological examination. ResultsCompared with solvent control group, after each administration of 2 h, the numbers of WBC and Lym in paclitaxtide injection groups were increased in different levels, and decreased after 24 and 72 h in a dose-dependent manner, and the numbers of that in 30 mg/kg groups after 72 h were significantly decreased（P〈0.05、0.01）. Although the number of RBC showed a decreasing trend with the increase of dose, there was no obvious difference in each dose group, and the range of fluctuation was small. The results of bone marrow smears indicated that bone marrow cells were scattered in each dose group of paclitaxtide injection compared with the solvent control group, and showed different degrees of change, Also, there were different degrees of hematopoietic suppression, and differences of 30 mg/kg groups were obvious. Histopathological examination showed that the hematopoietic suppression of bone marrow cavity was significant（P〈0.01） in the paclitaxtide injection 30 mg/kg group, while it was not significant in 3 and 10 mg/kg groups. Conclusion Paclitaxtide injection has toxic effects on the bone marrow hematopoietic system of Beagles, which was mainly manifested by the suppression of bone marrow hematopoiesis, especially in the 30 mg/kg groups.