骨髓间充质干细胞源性外泌体对小鼠放射性肠损伤的影响  

Effect of bone marrow mesenchymal stem cells-derived exosomes on radiation-induced intestinal injury in mice

作　　者：张亚红 马磊[2] 徐全晓[2] 李媛媛[2] ZHANG Yahong;MA Lei;XU Quanxiao;LI Yuanyuan(Graduate School of Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Henan Provincial Key Laboratory of Tumor Molecular Biology Medicine of Nanyang First People′s Hospital,Nanyang 473010,Henan Province,China)

机构地区：[1]新乡医学院研究生学院,河南新乡453003 [2]南阳市第一人民医院河南省肿瘤分子生物学医学重点实验室,河南南阳473010

出　　处：《新乡医学院学报》2025年第5期351-356,共6页Journal of Xinxiang Medical University

基　　金：苏州大学省部共建放射医学与辐射防护国家重点实验室项目(编号:GZK1202008)。

摘　　要：目的探讨骨髓间充质干细胞源性外泌体(BMSC-Exos)对小鼠放射性肠损伤的影响。方法将BALB/C小鼠随机分为正常组(n=5)、模型组(n=15)和BMSC-Exos组(n=15)。正常组小鼠不接受照射和外泌体移植;模型组小鼠仅接受照射处理;BMSC-Exos组小鼠接受照射后将BMSC-Exos溶液移植到其体内。正常组小鼠在照射后第1天全部处死,BMSC-Exos组和模型组小鼠于照射后第1、4、7天各处死5只并取肠组织及血清。采用苏木精-伊红(HE)染色观察3组小鼠小肠组织病理学变化,流式细胞术检测血清中炎症因子白细胞介素(IL)-6、IL-10、IL-12、单核细胞趋化蛋白-1(MCP-1)、γ干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)水平,原位末端转移酶标记染色法检测3组小鼠肠组织中细胞凋亡情况。结果HE染色结果显示,正常组小鼠肠上皮完整,绒毛形态规则,无明显炎症细胞浸润;模型组小鼠肠上皮完整性丧失,部分绒毛脱落,黏膜肌层变薄,可见炎症细胞浸润;BMSC-Exos组小鼠组织结构相对完好,绒毛相对完整,少见炎症细胞浸润。移植后第1天,模型组小鼠小肠绒毛高度显著低于正常组(P<0.05)。移植后第1天,模型组与BMSC-Exos组小鼠的小肠绒毛高度比较差异无统计学意义(P>0.05);移植后第4、7天,BMSC-Exos组小鼠的小肠绒毛高度显著高于模型组(P<0.05)。与正常组比较,模型组小鼠移植后第1天血清中促炎细胞因子IL-6、MCP-1、IFN-γ、TNF-α、IL-12水平显著升高,抗炎细胞因子IL-10水平显著下降(P<0.05)。移植后第1天,BMSC-Exos组与模型组小鼠血清中IL-6、MCP-1、IFN-γ、TNF-α、IL-12、IL-10水平比较差异无统计学意义(P>0.05)。移植后第4、7天,与模型组比较,BMSC-Exos组小鼠血清中IL-6、MCP-1、TNF-α、IL-12水平显著下降,IL-10水平显著升高(P<0.05)。模型组小鼠移植后第1天肠组织中凋亡细胞所占百分比显著高于正常组(t=-46.677,P<0.05)。移植后第1、4天,模型组与BMSC-Exos组Objective To investigate the effect of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on radiation-induced intestinal injury in mice.Methods BALB/C mice were randomly divided into a normal group(n=5),a model group(n=15)and a BMSC-Exos group(n=15).Mice in the normal group did not receive irradiation and exosome transplantation.Mice in the model group only received irradiation treatment.Mice in the BMSC-Exos group were transplanted with BMSC-Exos solution after irradiation.All mice in the normal group were killed on the first day after irradiation,and 5 mice in each of the BMSC-Exos and model groups were killed on the first,fourth and seventh days after irradiation.Then the intestinal tissues and serum of the killed mice were collected.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes of small intestines of mice in three groups.The levels of inflammatory factors such as interleukin(IL)-6,IL-10,IL-12,monocyte chemoattractant protein-1(MCP-1),interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α)in serum were detected by flow cytometry.Apoptosis in intestinal tissues of three groups of mice was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining.Results HE staining results showed that,in the normal group,the intestinal epithelium was intact,with regular-shaped villi and no obvious inflammatory cell infiltration.In the model group,the intestinal epithelium was not intact,with some villi falling off,a thinned muscularis mucosa,and evident inflammatory cell infiltration.In the BMSC-Exos group,the intestinal tissue structure of mice was relatively intact,with almost no villi falling off and rare infiltration of inflammatory cells.On the first day after transplantation,the height of small intestinal villi in the model group was significantly lower than that in the normal group(P<0.05),but not significantly different from that in the BMSC-Exos group(P>0.05).On the fourth and seventh days after transplantation,the height of small intestinal

关 键 词：骨髓间充质干细胞源性外泌体 放射性肠损伤 炎症 凋亡 

分 类 号：R818.85[医药卫生—放射医学]