目的 從臨床檢驗及病理學(xué)角度研究注射用紫衫肽對比格犬骨髓造血系統(tǒng)的毒性作用。方法 24只比格犬，每組6只，雌雄各半，分為溶劑對照組和紫杉肽注射液3、10和30 mg/kg組；注射用紫杉肽靜脈滴注給藥，以每21天為1個給藥周期，每個周期給藥1次，共9個周期。第1、5、9次給藥周期后約2、24、72 h取靜脈外周血，血液分析儀檢測紅細(xì)胞（RBC）、白細(xì)胞（WBC）和淋巴細(xì)胞（Lym），并進(jìn)行血涂片觀察；取股骨骨髓，進(jìn)行涂片分類計數(shù)；剖取胸骨切片、HE染色，進(jìn)行組織病理學(xué)檢查。結(jié)果 與溶劑對照組比較，注射用紫杉肽在每次給藥2 h后，各劑量組WBC、Lym出現(xiàn)不同程度升高，均呈劑量相關(guān)性；24、72 h后呈降低趨勢，72 h后30 mg/kg組均顯著降低（P<0.05、0.01）；RBC在各時間段隨著劑量的增加表現(xiàn)出一定的降低趨勢，但波動范圍較小，差異不顯著。涂片結(jié)果顯示，與溶劑對照組比較，注射用紫杉肽3、10、30 mg/kg組骨髓細(xì)胞呈稀松散在，出現(xiàn)不同程度造血抑制，30 mg/kg組差異明顯；組織學(xué)病理檢查顯示，注射用紫衫肽30 mg/kg組骨髓腔內(nèi)出現(xiàn)明顯造血抑制（P<0.01），而3、10 mg/kg組則造血抑制不明顯。結(jié)論 注射用紫杉肽對比格犬骨髓造血系統(tǒng)具有毒性作用，主要表現(xiàn)為骨髓造血抑制，3、10 mg/kg組呈抑制趨勢但差異不顯著，30 mg/kg組較明顯。

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. Results Compared 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.

國家科技重大新藥創(chuàng)制項目（2015ZX09501004）；天津市科技計劃項目（16PTGCCX00090）