趋磁细菌AMB-1对小鼠的生物相容性探究  

Exploration of the biocompatibility of magnetotactic bacteria AMB-1 in mice

作　　者：马晓雅 陈昌友[2] 宋涛[2] 马洁 袁伟 Ma Xiaoya;Chen Changyou;Song Tao;Ma Jie;Yuan Wei(State Key Laboratory of Molecular Oncology,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical Collage,Beijing 100021,China;Institute of Electrical Engineering,Chinese Academy of Sciences,Beijing 100190,China;Center of Biotherapy,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院、北京协和医学院肿瘤医院分子肿瘤学国家重点实验室,北京100021 [2]中国科学院电工研究所,北京100190 [3]北京医院生物治疗中心国家老年医学中心中国医学科学院老年医学研究院,北京100730

出　　处：《中国医学前沿杂志（电子版）》2024年第4期46-54,共9页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

基　　金：国家自然科学基金重点项目(51937011)。

摘　　要：目的在体外和体内条件下探究趋磁细菌AMB-1对BALB/c小鼠的生物相容性。方法透射电镜观察AMB-1形貌特征;显微镜拍摄AMB-1在血清中的运动,Image J计算运动速度;乳酸脱氢酶(lactate dehydrogenase,LDH)检测AMB-1对小鼠乳腺癌细胞4T1和成纤维细胞L929细胞毒性;流式细胞术评价AMB-1对BALB/c小鼠骨髓来源树突细胞成熟影响;改良寇氏法计算出AMB-1对BALB/c小鼠的半数致死剂量;普鲁士蓝染色BALB/c小鼠心、肝、脾、肺、肾脏器观察AMB-1在小鼠体内的分布情况;流式细胞术检测AMB-1对BALB/c小鼠脾脏树突细胞的影响;检测小鼠BALB/c血生化指标评估其安全性;苏木精-伊红染色BALB/c小鼠心、肝、脾、肺、肾脏器,观察其组织形态变化。结果37℃条件下,AMB-1在血清中可保持运动至少120 min;AMB-1菌量超过3.3×10^(6)个时,对小鼠乳腺癌细胞4T1和成纤维细胞L929具有毒性,随菌量增加,毒性越大;AMB-1可促进骨髓来源树突细胞CD86^(+)、CD80^(+)双阳细胞的比例增大。AMB-1对BALB/c小鼠半数致死剂量为2.59×10^(10)个。AMB-1对小鼠脾脏树突细胞成熟的影响随着时间延长逐渐减弱;血生化指标在正常范围内;小鼠主要脏器无明显组织形态学变化。结论趋磁细菌AMB-1具有良好生物相容性,在体内不会引发严重免疫炎症等不良反应,具有体内应用潜能。Objective To explore the biocompatibility of magnetotactic bacteria AMB-1 in BALB/c mice under in vitro and in vivo conditions.Methods The morphological characteristics of AMB-1 were observed in vitro using transmission electron microscopy(TEM).The morphology of AMB-1 was observed by transmission electron microscopy.The motion of AMB-1 in serum was captured by microscope,and the motion speed was calculated by Image J.The cytotoxicity of AMB-1 to mouse breast cancer cells 4T1 and mouse fibroblast cells L929 was assessed using the LDH assay.The effect of AMB-1 on BALB/c mouse bone marrow-derived dendritic cells(BMDC)was evaluated using flow cytometry.The median lethal dose(LD_(50))of AMB-1 in BALB/c mouse was calculated using the Karber's method.The distribution of AMB-1 in BALB/c mouse organs(heart,liver,spleen,lung,and kidney)was observed by Prussian Blue staining.The effect of AMB-1 on splenic dendritic cells(DC)in the BALB/c mouse spleen was detected by flow cytometry,the safety of AMB-1 was assessed by testing the biochemical indices in mouse serum.And the histological changes in the major organs of the mice were observed using Hematoxylin and Eosin staining.Results Under 37℃conditions,AMB-1 could maintain its movement in serum for at least 120 minutes.When the concentration of AMB-1 exceeded 3.3×10^(6),it was toxic to mouse mammary cancer cells 4T1 and fibroblasts L929,and the toxicity increased with the increase of bacteria amount.AMB-1 could promote the maturation of bone marrow-derived dendritic cells.The LD_(50) of AMB-1 for BALB/c mice was 2.59×10^(10).The effect of AMB-1 on the maturation of dendritic cells in the mouse spleen was gradually weakened with time.Blood biochemical indicators were within normal ranges.There were no significant histomorphological changes in the major organs of the mice.Conclusions Magnetotactic bacteria AMB-1 possess relatively good biocompatibility.They do not induce severe immune inflammation or other adverse reactions in vivo,demonstrating promising potential for in vi

关 键 词：趋磁细菌AMB-1 生物相容性 细胞毒性 半数致死剂量 

分 类 号：R318.08[医药卫生—生物医学工程]