骨髓间充质干细胞对小鼠动脉粥样硬化炎性反应的影响  

Effect of mysenchymal stem cells on the inflammatory response of atherosclerosis in mice

作　　者：王治校[1] 郑晓新[1] 王崇全[2] 李晓艳[1] 冯高科[1] 朱红玲[1] 蒋学俊[1] 

机构地区：[1]武汉大学人民医院心血管内科,430060 [2] 湖北医药学院附属十堰市太和医院心内科

出　　处：《中华生物医学工程杂志》2015年第3期201-205,共5页Chinese Journal of Biomedical Engineering

基　　金：湖北省自然科学基金（2014CFC1108）

摘　　要：目的 研究骨髓间充质干细胞（MSC）对小鼠动脉粥样硬化炎性反应的影响.方法 分离培养载脂蛋白E基因敲除（ApoE-/-）小鼠的骨髓MSC并进行鉴定.36只小鼠随机数字法分为3组：阴性对照（Neg）组（n=12）,阳性对照（Pos）组（n=12）和MSC移植（MSC）组（n=12）,3组小鼠均予高脂饮食喂养12周制作动脉粥样硬化动物模型.Pos组和MSC组小鼠分别经尾静脉注入DMEM培养液和MSC,每3周注射1次,持续12周.实验结束时处死小鼠,取小鼠脾脏、主动脉根部淋巴结组织和外周血检测CD4＋CD25＋调节性T细胞百分比和功能,免疫荧光组织化学检测主动脉根部斑块组织淋巴细胞和巨噬细胞浸润.酶联免疫吸附法（ELISA）检测3组小鼠血清高敏C反应蛋白（hs-CRP）、基质金属蛋白酶1（MMP-1）、干扰素γ（IFN-γ）、转化生长因子β（TGF-β）和白细胞介素10（IL-10）水平.结果 与Neg组、Pos组比较,MSC组小鼠脾脏及淋巴结组织CD4＋CD25＋/CD4＋比例显著升高,且脾脏Foxp3＋CD25＋/CD4＋比例也显著增加（均P＜0.05）.MSC组调节性T细胞抑制效应性T细胞增殖的能力显著增加.与Neg组、Pos组比较,MSC组小鼠血清TGF-β和IL-10水平升高,而IFN-γ、hs-CRP和MMP-1水平显著降低（均P＜0.05）.免疫荧光组织化学检测显示各组小鼠斑块组织中淋巴细胞和巨噬细胞浸润无明显差异.结论 MSC对动脉粥样硬化炎性反应具有抑制作用.Objective To explore the effect of mysenchymal stem cells （MSCs） on the inflammatory reactions of atherosclerosis in mice.Methods The bone marrow MSCs of hypercholesterolemic apoliprotein E knock-out （ApoE-/-） mice were isolated,cultured and identified.Thirtysix ApoE-/-mice were randomly divided into three groups of twelve：the negative control （Neg） group,the positive control （Pos） group,and the MSCs group.The animal models of atherosclerosis were established in the three groups by feeding with high-fat diet for 12 weeks.For once every 3 weeks during the 12-week period,the mice in the Pos group were injected with DMEM culture solution,and those in the MSCs group with MSC,via the tail vein.All mice were executed at the end of study,the percentage and function of CD4＋ CD25 ＋ regulatory T cells in splenocytes,aortic root lymph nodes and peripheral blood were analyzed.The lymphocyte and macrophage infiltration at the aortic root plaques were determined by fluorescence immunohistochemistry.ELISA was used to determine the levels of serum high sensitive C-reactive protein （hsCRP）,matrix metalloproteinase-1 （MMP-1）,interferon-γ （IFN-γ）,transforming growth factor β （TGF-β）,and interleukin-10（IL-10） in the three groups.Results Compared with control animals,MSCs injection resulted in a significant increase in the ratio of CD4＋CD25＋/CD4＋ in spleen and lymphatic tissues,as well as increase in the ratio of Foxp3 ＋ CD25 ＋/CD4＋ in spleen （all P〈0.05）.In the MSC group,we observed remarkably enhanced suppression of effector T cell proliferation by regulatory T cells.Compared with Neg and Pos groups,the mice in MSC group had higher levels of serum TGF-β and IL-10,and lowered levels of IFN-γ,hs-CRP and MMP-1 （all P〈0.05）.Fluorescence immunohistochemistry did not show any difference in lymphocyte and macrophage infiltration of the plagues among three groups.Conclusion Mysenchymal stem cells plays an important role in anti-inflammatory response within the atherosc

关 键 词：间充质干细胞 动脉粥样硬化 调节性T细胞 炎症 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]