目的 探讨健康及炎性环境中牙周膜干细胞(periodontal ligament stem cell,PDLSCs)分泌的外泌体对小鼠结肠炎的治疗作用,评价其免疫抑制能力差异.方法 分离培养牙周膜干细胞,于正常及含10％脂多糖(lipopolysaccharide,LPS)环境下进行培养12小时,并提取其分泌的外泌体.使用含2.5％C(dextran sμlfate sodiμm salt,DSS)的饮水诱导C57BL/6小鼠结肠炎,并使用提取的外泌体进行尾静脉注射进行治疗,20只小鼠分为4组:对照组,肠炎组(DSS),健康牙周膜干细胞外泌体(DSS+n-Exo)治疗组,炎性牙周膜干细胞外泌体(DSS+i-Exo)治疗组,通过小鼠体重分析、结肠大体观察及结肠病理学检测,评价两种外泌体对小鼠结肠炎的治疗作用.结果 ①在正常及炎性环境下,牙周膜干细胞均能分泌外泌体;②小鼠体重检测显示,与肠炎组小鼠相比,外泌体注射组小鼠体重下降较少(DSS+n-Exo vs DSSP＜0.01,DSS+i-Exo vs DSSP＜0.05),n-Exo治疗组小鼠体重较i-Exo治疗组下降较少(P＜0.05);③小鼠结肠大体观显示,肠炎组小鼠结肠血便明显,肠壁变薄,外泌体注射组小鼠结肠血便程度较轻;④小鼠结肠HE染色结果显示,相较于对照组,DSS饮水小鼠结肠黏膜层均表现不同程度的炎细胞浸润及黏膜下层松解破坏;相较于DSS组及DSS+i-Exo组,DSS+n-Exo组黏膜炎细胞浸润及黏膜下层组织松解程度较轻.结论 牙周膜干细胞来源的外泌体对小鼠结肠炎有一定的治疗效果,并且炎性环境来源的外泌体免疫抑制能力下降.
Effective of exosomes derived from PDLSCs in different environments in the treatment of colitis in mice
Objective To investigate the therapeutic effect of exosomes secreted by PDLSCs on colitis in mice in healthy and inflammatory environments,and to evaluate the difference in immunosuppressive ability.Methods The PDLSCs were isolated and cμltured in the normal and 10％LPS environment for 12 hours,and the secreted exosomes were extracted.Mice colitis was induced by drinking water containing 2.5％DSS and treated with extracted exosomes by tail vein injection.Twenty C57BL/6 mice were divided into four groups:Control group,DSS group,DSS+n-Exo group,DSS+i-Exo group,body weight analysis,colonic gross view and colonic pathology detection were used to evaluate the therapeutic effects of two kinds of exosomes.Results ①Under normal and inflammatory conditions,PDLSCs coμld secrete exosomes.②Body weight analysis showed that compared with DSS group,body weight of exosomes injection group decreased less(DSS+n-Exo vs DSS P＜0.01,DSS+i-Exo vs DSS P＜0.05),and n-Exo group decreased less than i-Exo group(P＜0.05).③The colonic gross view showed that the colonic blood stool was obvious and the intestinal wall was thinner in the DSS group,and less severe were observed in the exosome injection group.④The resμlts of HE staining showed that compared with the control group,the colonic mucosa of DSS drinking groups showed different level of inflammatory cell infiltration and submucosal lysis.Compared with DSS group and DSS+i-Exo group,the mucositis cell infiltration and submucosal tissue lysis in DSS+n-Exo group was less.Conclusion Exosomes derived from PDLSCs have a certain therapeutic effect on colitis in mice and the immunosuppressive ability of exosomes from inflammatory environment is decreased.
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