新型脆弱拟杆菌ZY-312多糖TP2安全性评价  

Safety evaluation of a novel strain of Bacteriodes fragilis polysacchride TP2

作　　者：邓慧敏 杨斯琪[5] 毕玉晶 刘洋洋[2] 王晔 白杨 杨瑞馥[4] 智发朝[2,3] DENG Huimin;YANG Siqi;BI Yujing;LIU Yangyang;WANG Ye;BAI Yang;YANG Ruifu;ZHI Fachao(Department of Gastroenterology,Huizhou Central People′s Hospital,Huizhou,516000;Guangzhou ZhiYi biotechnology Co.Ltd.,Guangzhou,510515;Guangdong Provincial Key Laboratory of Gastroenterology,Department of Gastroenterology,Institute of Gastroenterology,Nanfang Hospital,Southern Medical University,Guangzhou,510515;State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,Beijing,100071;Department of Gastroenterology,Nanfang Hospital Zengcheng Campus,Southern Medical University,Guangzhou,511340)

机构地区：[1]惠州市中心人民医院消化内科,516000 [2]广州知易生物科技有限公司,510515 [3]南方医科大学南方医院消化病学研究所消化内科广东省消化病学重点实验室,510515 [4]军事医学科学院、微生物与流行病学研究所、病原与生物安全国家重点实验室,100071 [5]南方医科大学南方医院增城院区消化内科,511340

出　　处：《现代消化及介入诊疗》2024年第10期1173-1179,共7页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：广州市科技计划项目重点研发计划2024年度农业和社会发展科技专题(2024B03J1282)。

摘　　要：目的通过细胞实验及动物实验评价一株新型脆弱拟杆菌ZY-312菌株表面多糖TP2的安全性。方法通过MTT法及实时细胞分析仪器检测不同剂量浓度的TP2对LoVo、SW480、HT-29细胞系的存活、黏附、增殖影响以检测TP2细胞毒性;给予SPF级6~8周龄BALB/c小鼠灌服50μg TP240次(隔日1次,共80日),监测一般情况、评估脏器病理、检测血清炎症因子及肠道菌群变化评估TP2对活体动物的影响。结果不同剂量(10~1000μg/mL)对结肠细胞系的存活、黏附、增殖无显著影响;长期服用TP2不导致小鼠腹泻、体重下降,不引起脏器病理变化,不引起血清炎症因子升高,并能显著增加小鼠肠道菌群的多样性,增加Bacteroidete、Muribaculaceae、Prevotellaceae等肠道菌群的丰度,展示了其调节肠道菌群的作用。结论脆弱拟杆菌ZY-312表面多糖TP2具有细胞及动物安全性,有望成为一种应用于临床的新型生物制剂。Objective To evaluate the safety of polysaccharide TP2 of a novel strain of Bacteroides fragilis ZY-312 through cellular and animal experiments.Methods With the use of MTT assay and Real-time cell analysis instrument to detect the effects of different doses of TP2 on the survival,adhesion and proliferation of LoVo,SW480 and HT-29 cell lines to detect the cytotoxicity of TP2.To detect animal toxicity,SPF level Balb/C mice ranging from 6-8 week old were administrated with 50μg TP240 times(once every other day for 80 days).The effects of TP2 on living animals were evaluated by general condition,organs structure and pathology,serum inflammatory factors,and influences on intestinal flora.Results Different doses(10-1000μg/mL)TP2 did not significantly affect the survival,adhesion and proliferation of colon cell lines.Long-term use of TP2 did not cause diarrhea,weight loss,pathological changes of organs and inflammatory factors increase in mice.Furthermore,TP2 significantly increases the diversity of intestinal flora of mice,including increasing the abundance of Bacteroidete,Muribaculaceae,Prevotellaceae and so on,indicting its active role in regulating intestinal flora.Conclusion The surface polysaccharide TP2 of Bacteroides fragilis ZY-312 is safe to cells and animals,and is expected to be a novel biological agent for clinical application.

关 键 词：脆弱拟杆菌 多糖A 安全性评价 肠道菌群 

分 类 号：R378.2[医药卫生—病原生物学] R57[医药卫生—基础医学]