目的 研究長期重復(fù)給予注射用酒石酸長春瑞濱膠束（NVB-m）對Beagle犬肝、腎毒性的影響，同時設(shè)同類市售注射用酒石酸長春瑞濱（NVB）進行毒性比較研究。方法 Beagle犬48只，按體質(zhì)量、性別隨機分為對照組、空白膠束組、NVB組和NVB-m 6、12、24 mg/m²組，每組8只。NVB組給予24 mg/m²劑量的NVB，空白膠束組給予相同濃度的空白膠束，對照組給予生理鹽水，靜脈給藥。進行一般狀態(tài)觀察，稱取Beagle犬體質(zhì)量，取血檢測血清生化指標，采集尿液檢測尿常規(guī)，大體解剖稱量肝、腎質(zhì)量，計算臟器系數(shù)并做組織病理學(xué)檢查。結(jié)果 一般癥狀檢查可見，NVB組、NVB-m 12、24 mg/m²組在給藥期間有食欲不振、食量減少甚至拒食等癥狀，隨給藥次數(shù)增加而減輕。動物體質(zhì)量在試驗期間未見明顯異常。血清生化檢查可見，與對照組比較，給藥期間NVB組及NVB-m 6、12、24 mg/m²組天冬氨酸轉(zhuǎn)氨酶（AST）、天冬氨酸轉(zhuǎn)氨酶（ALT）、總膽紅素（TBIL）升高，總蛋白（TP）、白蛋白（ALB）降低，其中NVB-m 24 mg/m²組對動物TP影響較NVB組輕微；NVB組及NVB-m 24 mg/m²組動物ALT升高（部分組別部分時間差異顯著P<0.05、0.01），恢復(fù)期可恢復(fù)正常。尿生化檢查、大體解剖及臟器質(zhì)量檢查、組織病理學(xué)檢查未見明顯異常。結(jié)論 NVB-m長期給藥對Beagle犬有輕微肝毒性，主要表現(xiàn)為肝功指標異常；NVB-m對Beagle犬無腎毒性；NVB-m與NVB沒有明顯肝、腎毒性差異。

Objective To research the effect of repeated intravenous injection of vinorelbine tartrate micelles for injection (NVB-m) on hepatotoxicity and nephrotoxicity of Beagle dogs. At the same time, a comparative study on the toxicity of marketed vinorelbine tartrate for injection (NVB) was conducted.Methods 48 Beagle dogs were randomly divided into physiological control group, blank micelle group, market control group (NVB) and NVB-m 6, 12, 24 mg/m² dose group, with 8 dogs in each group. The market control group was given 24 mg/m² dose of NVB. The blank micelle group was given the same concentration of blank micelles as the drug group. Physiological saline was given to the physiological control group, intravenous administration. Beagle dogs were weighed, blood biochemical indexes were detected, urine routine was detected, liver and kidney weights were measured with gross anatomy, organ coefficient was calculated and histopathological examination was done. Results General symptoms test showed that NVB group, NVB-m 12, 24 mg/m² group had symptoms such as loss of appetite, decreased food intake and even antifeeding during the course of administration, which were alleviated with the increase of dosage times. There was no obvious abnormality in body weight during the experiment. Blood biochemical examination showed that AST, ALP, TBIL increased, TP and ALB decreased in NVB group and NVB-m 6, 12, 24 mg/m² group, of which NVB-m 24 mg/m² group had slight effect on TP, NVB group and NVB-m 24 mg/m² group could increase ALT. Urine biochemical examination, gross anatomy and viscera weight examination, histopathological examination showed no obvious abnormality. Conclusions NVB-m had slight hepatotoxicity to Beagle dogs, mainly showing abnormal liver function index; NVB-m had no nephrotoxicity to Beagle dogs; NVB-m and NVB had no significant difference in hepatotoxicity and nephrotoxicity.

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