去甲斑蝥素对喜树碱引起的白细胞减少症的缓解作用

目的:观察去甲斑蝥素(norcantharidin,NCTD)能否缓解喜树碱(camptothecin,CPT)用药引起的骨髓抑制。方法:取Balb/c小鼠,采用概率单位法计算CPT半数致死量(median lethal dose,LD50)。以1 mg·kg-1作为CPT给药剂量,使用全血分析仪检测24 h内不同时间点白细胞浓度变化,为后续联合用药提供检测时间点参考。随后取Balb/c小鼠随机分为6组,分别为空白组,CPT(1 mg·kg-1)组,NCTD低、高剂量(10,20 mg·kg-1)组,CPT(1 mg·kg-1)+NCTD(10 mg·kg-1)组和CPT(1 mg·kg-1)+NCTD(20 mg·kg-1)组。连续灌胃2周,采用眼球采血法,应用全血分析仪检测进行相关指标的测定。流式细胞仪检测各组小鼠骨髓中性粒细胞的差异。病理组织切片评估肠道的毒性情况。结果:CPT LD50为1 mg·kg-1。CPT单独给药后6 h小鼠白细胞数目降至最少。24 h内与CPT单独用药比较,CPT+NCTD联合给药组白细胞、中性粒细胞数目明显上升(P0.05),嗜酸性粒细胞、嗜碱性粒细胞等无明显变化。连续灌胃2周,比较CPT单独用药,CPT+NCTD联合给药组白细胞数目明显上升(P0.05),其中淋巴细胞升高显著(P0.01),其他细胞无明显变化。流式细胞仪检测各组小鼠骨髓中性粒细胞的无明显差异,苏木素-伊红(HE)染色显示CPT主要毒靶器官小肠的病理变化短期、长期均不明显。结论:NCTD可减轻CPT用药引起的白细胞减少症,并没有增加其肠道毒性,为临床CPT应用,并减轻其毒性提供一定理论参考。

Effect of Norcantharidin in Alleviating Camptothecin-induced Myelosuppression

Objective: To explore whether norcantharidin (NCTD) could reduce camptothecin (CPT)-caused myelosuppression. Method: Balb/c mice were collected. Probit analysis was made to calculate CPT median lethal dose (LD₅₀). With 1 mg·kg^-1 dose as CPT, whole blood analyzer was used to detect white blood cell(WBC) concentration at different time points within 24 h, so as to provide a reference for the subsequent detection time point in the subsequent combined administration. Subsequently, Balb/c mice were randomly divided into six groups:control group, CPT (1 mg·kg^-1) group, low-dose NCTD (10 mg·kg^-1) group, high-dose NCTD (20 mg·kg^-1) group, CPT (1 mg·kg^-1) + low-dose NCTD (10 mg·kg^-1) group and CPT (1 mg·kg^-1) + high-dose NCTD (20 mg·kg^-1) group. After continuous gavage for 2 weeks, eyeball sampling method and whole blood analyzer were used to measure relevant indicators. Flow cytometry was used to detect the differences of bone marrow neutrophils in each group. Histopathological sections evaluated the intestinal toxicity. Result: The CPT LD₅₀ is 1 mg·kg^-1.The number of white blood cells in mice was reduced to a minimum at 6 h after the single administration with CPT. Within 24 hours after the single treatment with CPT, the numbers of leukocytes and neutrophils in CPT and NCTD combined groups increased significantly (P<0.05), with no significant change in the number of eosinophils and basophils. After continuous gavage for 2 weeks, compared with the single treatment with CPT, the number of white blood cells in CPT and NCTD combined groups also increased significantly (P<0.05), and lymphocyte was significantly increased (P<0.01). No significant changes were observed in other cells. No significant difference in the mouse bone marrow neutrophil was detected by flow cytometry, hematoxylin-eosin (HE) staining showed no significant short-term or long-term pathological changes in intestine, the main target organ of toxicity of camptothecin. Conclusion: Norcantharidin can reduce the incidence of leucopenia caused by camptothecin, without increasing the intestinal toxicity. It provides a theoretical reference for the clinical application of camptothecin and its toxicity reduction.