炎症预激活骨髓间充质干细胞条件培养基调控急性辐射损伤小肠炎症反应的作用  

Conditioned medium derived from bone marrow mesenchymal stem cells with inflammatory activation regulates inflammatory response to acute radiation-induced intestinal injury

作　　者：郑跃 马发鑫 李金亮 卢铨 骆昱均 沙卫红 陈浩 Zheng Yue;Ma Faxin;Li Jinliang;Lu Quan;Luo Yujun;Sha Weihong;Sha Weihong(Second Clinical Medical College of Southern Medical University, Guangzhou 510280, Guangdong Province, China;Department of Gastroenterology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, Guangdong Province, China)

机构地区：[1]南方医科大学第二临床医学院,广东省广州市510280 [2]广东省人民医院(广东省医学科学院)消化内科,广东省广州市510080

出　　处：《中国组织工程研究》2019年第13期1969-1974,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81300279;81741067);项目负责人:陈浩;广东省自然科学基金(2016A030313815);项目负责人:沙卫红;广东省自然科学基金(2017A030313464);项目负责人:陈浩;广东省科技计划项目(2015A020212029);项目负责人:陈浩;广州市科技计划项目(201707010419);项目负责人:沙卫红;广州市科技计划项目(201804010050);项目负责人:陈浩~~

摘　　要：背景:骨髓间充质干细胞具有强大的免疫调节和抗炎能力。前期实验发现,炎症预激活骨髓间充质干细胞条件培养基可促进急性辐射小肠损伤结构和功能的修复,但其对急性辐射小肠损伤炎症反应的作用机制尚未完全明确。目的:探讨炎症预激活骨髓间充质干细胞条件培养基对急性辐射小肠损伤炎症反应的影响。方法:随机将80只SD大鼠(中山大学北校区实验中心提供)分为对照组、单纯辐射损伤组、辐射损伤+正常间充质干细胞条件培养基治疗组(IR+MSC-CM^(IEC-6(NOR))组)、辐射损伤+辐射炎症预激活间充质干细胞条件培养基治疗组(IR+MSC-CMIEC-6(IR)组),每组20只。使用尾静脉联合腹腔给药,辐射后第1, 3, 5, 7天,取小肠组织行苏木精-伊红染色观察小肠组织学变化,取小肠组织及血清采用ELISA检测炎症因子水平,辐射后第3天取小肠肠系膜淋巴结组织用流式细胞仪检测CD4^+Foxp3^+Treg细胞数量百分比。结果与结论:①与甲单纯辐射损伤组和正常间充质干细胞条件培养基治疗组相比,辐射炎症预激活间充质干细胞条件培养基组小肠上皮绒毛及隐窝结构明显改善;小肠组织中前炎症因子如白细胞介素1β、白细胞介素6和肿瘤坏死因子。水平显著减少,抗炎因子白细胞介素10水平显著升高;血清中前炎因子ActivinA、白细胞介素1β、白细胞介素6和肿瘤坏死因子α水平显著减少,抗炎因子白细胞介素10水平显著升高,以辐射后第3天最为明显;小肠肠系膜淋巴结中CD4^+Foxp3^+Treg细胞数量百分比显著升高,差异均有显著性意义;②上述结果表明,辐射炎症预激活间充质干细胞条件培养基能调控前炎因子和抗炎因子的平衡,增加小肠肠系膜淋巴结中CD4^+Foxp3^+Treg细胞数量,抑制急性辐射小肠损伤全身水平及小肠黏膜的炎症反应,促进小肠黏膜损伤的修复。BACKGROUND: Bone marrow mesenchymal stem cells(MSCs) have powerful anti-inflammatory and immunomodulatory properties. Our previous experiments have demonstrated that conditioned medium from bone marrow MSCs with inflammatory activation(MSC-CMIEC-6(IR))could improve the structural and functional repair of the small intestine after acute radiation-induced intestinal injury, but its effects on the inflammatory response to acute radiation-induced intestinal injury have not been elucidated.OBJECTIVE: To investigate the effects of MSC-CM on the inflammatory response to acute radiation-induced intestinal injury.METHODS: Eighty Sprague-Dawley rats(provided by the experimental center of the North Campus of Sun Yat-Sen University in China) were randomly divided into four groups(n=20/group): control group, irradiation(IR) group, irradiation+MSC-CMIEC-6(NOR) group(IR+MSC-CMIEC-6(NOR group) and irradiation+MSC-CMIEC-6(IR) group(IR+MSC-CMIEC-6(IR) group), followed by continuous administration via the tail vein and abdominal cavity. Intestinal tissue and serum samples were collected 1, 3, 5, 7 days after radiation for hematoxylin-eosin staining and analysis of the concentrations of inflammatory factors using ELISA. Mesenteric lymph nodes were collected 3 days after radiation for analysis of the percentage of CD4+Foxp3+Treg cells using flow cytometry.RESULTS AND CONCLUSION: Compared with the IR group and IR+MSC-CMIEC-6(NOR) group, the intestinal structure(small intestine epithelial villi and crypt) was significantly improved and the pro-inflammatory factors such as interleukin-1 β, interleukin-6 and tumor necrosis factor-a in the small intestine were significantly decreased in the IR+MSC-CMIEC-6(IR) group, whereas the level of anti-inflammatory factor interleukin-10 was significantly increased. Similarly, the levels of pro-inflammatory factors such as Activin A, interleukin-1β, interleukin-6 and tumor necrosis factor-a in the serum samples were significantly decreased and the level of anti-inflammatory factor IL-10 was signifi

关 键 词：骨髓间充质干细胞 条件培养基 细胞治疗 炎症 炎症反应 炎症因子 国家自然科学基金 间质干细胞 培养基 条件性 放射性 小肠 组织工程 

分 类 号：R459.9[医药卫生—治疗学] R394.2[医药卫生—临床医学]