骨髓间充质干细胞调节心脏移植大鼠的免疫功能

摘要

BACKGROUND:Heart transplantation is an effective method for treatment of end-stage heart failure, but immune rejection that seriously impact therapeutic effacicy is easy to occur after transplantation. OBJECTIVE:To investigate the regulatory effect of bone marrow mesenchymal stem cel s on the immune function of rats undergoiong heart transplantation. METHODS:Twenty Lewis rats were enrol ed as donors, and 20 Wistar rats as recipients. Heart transplantation models were established in the Wistar rats. These 20 model rats were randomized into cel transplantation and control group with 10 rats in each group. Forty-eight hours after heart transplantation, rats in the cel transplantation group were given bone marrow mesenchymal stem cel suspension (1 mL, 2×108 cel s/L) via the tail vein, while rats in the control group were given normal saline in the same dose. Then, the expression levels of serum interleukin-2, interleukin-10 and percentage of CD4+, CD8+, CD4+/CD8+, CD4+CD25high, CD4+CD25high Foxp3+T cel s in the venous blood were detected in the two groups at 7 days after cel transplantation. Additional y, rat myocardial tissues were taken and observed pathological y. RESULTS AND CONCLUSION:The survival time of the cel transplantation group was significantly longer than that of the control group (P<0.05). The expression level of interleukin-2 showed no significant difference between the two groups (P>0.05), but the level of interleukin-10 in the cel transplantation group was significantly higher than that in the control group (P<0.05). Compared with the control group, the percentage of CD4+/CD8+, CD4+CD25high, CD4+CD25high Foxp3+and CD4+T cel s was significantly higher, and the percentage of CD8+T cel s was significantly lower in the cel transplantation group (P<0.05). Histopathological findings showed that there were a smal amount of infiltrated lymphocytes in the cel transplantation group with the presence of slight bleeding and edema, and these inflammatory reactions were milder than those in the control group. These findings indicate that bone marrow mesenchymal stem cel transplantation can effectively reduce the rejection in rats undergoing heart transplantation.%背景：心脏移植是治疗终末期心力衰竭等疾病的有效手段，但移植后容易出现免疫排斥反应，严重影响到移植效果。　　目的：探讨骨髓间充质干细胞对心脏移植大鼠免疫功能的调节作用。　　方法：Lewis大鼠20只作为供体，Wistar大鼠20只作为受体，采用套管法建立大鼠颈部心脏移植模型。模型制备后，20只Wistar大鼠随机分为细胞移植组与空白对照组，每组10只。心脏移植后48 h，细胞移植组经尾静脉注射骨髓间充质干细胞悬液1 mL(细胞浓度为2×108 L-1)，空白对照组经尾静脉注射等量的生理盐水注射液。细胞移植后7 d，ELISA法检测血清白细胞介素2、白细胞介素10水平，流式细胞术检测大鼠静脉血中CD4+、CD8+、CD4+/CD8+、CD4+CD25high、CD4+CD25high Foxp3+T细胞百分含量，获取心肌组织进行病理学观察。　　结果与结论：①细胞移植组心脏存活时间显著长于空白对照组(P<0.05)；②两组血清白细胞介素2水平差异无显著性意义(P>0.05)，细胞移植组血清白细胞介素10水平显著高于空白对照组(P<0.05)；③细胞移植组CD4+、CD4+/CD8+、CD4+CD25high、CD4+CD25high Foxp3+T细胞占总淋巴细胞的比例均显著高于空白对照组(P<0.05)，CD8+T细胞占总淋巴细胞的比例显著低于空白对照组(P<0.05)；④细胞移植组心肌组织中有少量淋巴细胞浸润，心肌间质可观察到轻微出血和水肿，较空白对照组炎性反应程度较轻；⑤结果表明，对心脏移植大鼠实施骨髓间充质干细胞治疗可以有效减轻排斥反应。