目的 利用斑马鱼模型评价血必净注射液与3种抗生素并用对肝脏损伤的影响。方法 以肝脏荧光标记的斑马鱼为动物模型，设置对照组、抗生素单用（阿莫西林克拉维酸钾分散片1 000 μg/mL、左氧氟沙星片800 μg/mL、阿莫西林胶囊400 μg/mL）组、血必净注射液（2.5、5.0、10.0 μg/mL）＋抗生素组，连续给药72 h，每24 h更换暴露液，给药结束后，显微镜下拍照，统计肝面积、肝脏荧光强度。收集样品，石蜡包埋，切片，HE染色，进行组织病理学检查。结果 在阿莫西林克拉维酸钾分散片和血必净注射液的安全浓度范围内联合用药未发现斑马鱼死亡，未发现毒性加剧；在左氧氟沙星片和血必净注射液的安全浓度范围内联合用药未发现斑马鱼死亡，未发现毒性加剧；在阿莫西林胶囊的安全浓度范围内，联合应用10 μL/mL血必净注射液可导致斑马鱼全部死亡；联合应用5 μL/mL血必净注射液可导致部分斑马鱼死亡，剩余斑马鱼肝毒性加剧，与阿莫西林胶囊单用组比较，肝面积及肝脏荧光强度均显著下降（P<0.05）。结论 血必净注射液与阿莫西林克拉维酸钾分散片、左氧氟沙星片并用不会对斑马鱼的肝脏造成损伤。阿莫西林胶囊与血必净注射液并用时增加斑马鱼的肝损伤风险，应控制阿莫西林胶囊的处方浓度，并重点观察患者肝功能变化。

Objective To evaluate the effects of Xuebijing Injection and three kinds of antibiotics on liver protection and liver injury by zebrafish model. Methods Zebrafish with liver fluorescent labeling were used as animal models. The control group, single antibiotic group (amoxicillin clavulanate potassium dispersible tablet 1 000 μg/mL, levofloxacin tablet 800 μg/mL, amoxicillin capsule 400 μg/mL), Xuebijing Injection (2.5, 5.0, 10.0 μg/mL) + antibiotic group were set for continuous administration for 72 h. Change the exposure solution every 24 hours, After administration, the liver area, and liver fluorescence intensity were counted. Samples collection, paraffin embedding, paraffin section, HE staining, and histopathological examination were performed. Results The experimental results showed that there were no death and no aggravation of toxicity within the safe dose range of amoxicillin-clavulanate potassium, combing with Xuebijing (2.5, 5, 10 μL/mL). With the increasing of Xuebijing concentration, the liver area and fluorescence intensity increased gradually. Within the safe dose range of levofloxacin, no increase in toxicity was found combing with Xuebijing (2.5, 5, 10 μL/mL). Within the safe concentration range of amoxicillin, combined application of 10 μL/mL Xuebijing Injection could cause death of all zebrafish. The combined application of 5 μL/mL Xuebijing Injection could cause the death of some zebrafish, and the liver toxicity of the remaining zebrafish was aggravated. Compared with the group of amoxicillin capsule alone, the liver area and liver fluorescence intensity were significantly decreased (P < 0.05). Conclusion The combined use of Xuebijing Injection and amoxicillin-clavulanate potassium will not cause damage to the liver of zebrafish. The combined use of amoxicillin and Xuebijing Injection will increase the risk of liver injury in zebrafish, and high doses may lead to death. When using Xuebijing Injection clinically, the prescribed dose of amoxicillin should be controlled and the changes in liver function should be observed. The combined use of Xuebijing Injection and levofloxacin has not found any damage to the liver of zebrafish.

国家“万人计划”（2016）经费资助项目（W02020052）；中国博士后科学基金面上项目（2020M670236、2021T140075）；国家自然科学基金青年项目（81803963）