基于斑马鱼模型的新阿胶对化疗诱导免疫损伤的保护作用  

Protective effect of Pig-hide Gelatin on chemotherapy-induced immune injury based on the zebrafish model

作　　者：张友刚 刘发生[2,3] 孔浩天 武勇 张爱平 田青平[2] 刘可春[4] 韩利文 ZHANG You-gang;LIU Fa-sheng;KONG Hao-tian;WU Yong;ZHANG Ai-ping;TIAN Qing-ping;LIU Ke-chun;HAN Li-wen(School of Pharmacy and Pharmaceutical Science,Shandong First Medical University,Shandong Academy of Medical Sciences,Jinan 250117,China;School of Pharmaceutical Science of Shanxi Medical University,Taiyuan 030001,China;Jinggangshan University,Jinggangshan 343009,China;Qilu University of Technology,Biology Institute of Shandong Academy of Sciences,Jinan 250103,China;Shandong Fupai E-jiao Co.LTD,Jinan 250100,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)药学与制药科学学院,济南250117 [2]山西医科大学药学院,太原030001 [3]井冈山大学,江西井冈山343009 [4]齐鲁工业大学(山东省科学院)山东省科学院生物研究所,济南250103 [5]山东福牌阿胶股份有限公司,济南250100

出　　处：《中华中医药杂志》2021年第9期5550-5555,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：中央本级重大增减支项目(No.2060302-1907-09);山东省自然科学基金项目(No.ZR2019MH037);国家重点研发计划(No.2018YFC1707301)。

摘　　要：目的:探讨新阿胶对化疗所致免疫损伤的保护作用。方法:以斑马鱼为实验动物模型,采用长春瑞滨、雷帕霉素、氯霉素3种药物处理,建立斑马鱼免疫损伤模型;采用静脉微量注射印度墨水法建立斑马鱼巨噬细胞吞噬功能评价模型;观察不同浓度的新阿胶对3种药物造成的免疫损伤斑马鱼中性粒细胞和巨噬细胞的影响。采用实时荧光定量PCR方法检测免疫相关细胞因子白细胞介素(IL-6)、IL-8、IL-10、肿瘤坏死因子(TNF-α)、γ干扰素(IFN-γ)基因mRNA水平的变化。结果:50、100μg/mL新阿胶显著逆转了长春瑞滨、雷帕霉素、氯霉素诱导的斑马鱼中性粒细胞数量的减少(P<0.01),100μg/mL新阿胶提升了斑马鱼巨噬细胞的吞噬能力(P<0.01)。与造模组比较,新阿胶组IL-6、IL-8、IL-10、IFN-γmRNA表达水平显著升高(P<0.01),TNF-αmRNA表达水平显著降低(P<0.01)。结论:新阿胶对化疗药物所致免疫损伤具有一定的保护作用,其机制可能与促进免疫细胞增殖和增强巨噬细胞吞噬功能有关。Objective: To explore the protective effect of Pig-hide Gelatin(PHG) on immune injury caused by chemotherapy. Methods: The zebrafish was used as the experimental animal model. Three chemotherapeutic drugs including vinorelbine, rapamycin and chloramphenicol were used to establish a zebrafish immune injury model. The phagocytic function of zebrafish macrophages was evaluated by microinjection of Indian ink. To observe the effect of different concentrations of PHG on the immune damage of zebrafish neutrophils and macrophages caused by three kinds of chemotherapy drugs. The mRNA levels of IL-6, IL-8, IL-10, TNF-α and IFN-γ genes were detected by qPCR. Results: At the concentration of 50μg/mL and 100μg/mL,PHG significantly reduced the damage of vinorelbine, rapamycin and chloramphenicol to zebrafish immune cells(P<0.01), and 100μg/mL PHG promoted the phagocytosis of zebrafish macrophages(P<0.01). Compared with vinorelbine group, the mRNA expression of IL-6, IL-8, IL-10 and IFN-γ gene in PHG group was significantly higher(P<0.01), and TNF-α mRNA expression in PHG group decreased(P<0.01). Conclusion: PHG has protective effect on immune injury induced by chemotherapy, and its mechanism may be related to promoting the proliferation of immune cells and enhancing the phagocytic function of macrophages.

关 键 词：新阿胶 化疗 免疫损伤 斑马鱼 中性粒细胞 巨噬细胞 实时荧光定量PCR 

分 类 号：R285.5[医药卫生—中药学]