间充质干细胞移植对小鼠动脉粥样斑块形成的影响

Effects of MSCs on the progression of atherosclerosis plaque in ApoE-knock out mice

目的:研究间充质干细胞移植对ApoE-/-小鼠动脉粥样斑块形成的影响。方法:分离培养ApoE-/-小鼠骨髓间充质干细胞(MSCs),并进行鉴定。将30只ApoE-/-小鼠分为阴性对照组、阳性对照组、MSCs移植组,每组10只,阳性对照组和MSCs移植组从尾静脉注射MSCs。比较各组小鼠的斑块面积;分析各组小鼠不同组织中CD4+CD25+Treg细胞的数目和功能;利用ELISA法检测各组小鼠脾细胞炎性因子浓度。结果:与对照组比较,MSCs移植组小鼠斑块面积明显缩小(P<0.05),CD4+CD25+Treg细胞的数目显著增加(P<0.05),CD4+CD25+Treg细胞增殖反应下降;上清液中TGF-β和IL-10浓度显著升高,而IFN-γ浓度显著下降。结论:MSCs移植可能通过调控体内炎症反应而产生抗动脉粥样硬化作用。

AIM： To explore the effects of mesenchymal stem cells in the formation of atherosclerosis plaque in hypercholesterolemic apoliprotein（apo）E-/-mice.METHODS： ApoE-/-mice mesenchymal stem cells（MSCs） were isolated and identified.Thirty ApoE-/-mice were divided into negative control group（Neg,n=10）,positive control group（Pos,n=10） and MSCs group（n=10）.MSCs were injected through caudal vein into the body of Pos and MSCs groups.The plaque area of all subjects were compared,the percentage of CD4＋CD25＋ regulatory T cells in different tissues were analyzed by FACS,proliferation response of splenocytes to mesenchymal stem cells and cytokines in the supernatant were determined by ELISA.RESULTS： Compared with controls,MSCs resulted in a significant decrease of the atherosclerotic plaques size（P〈0.05）,and a significant increase of CD4＋CD25＋ regulatory T cells in spleen（P〈0.05）.Specific proliferation response of CD4＋CD25＋ regulatory T cells in splenocytes to MSCs was significantly suppressed.The supernatant levels of TGF-β and IL-10 in MSCs group were increased while IFN-γ decreased significantly.CONCLUSION： MSCs play an important role in regulating the inflammatory response and may significantly inhibit the formation of the atherosclerosis plaque in ApoE-/-mice.