受者同系骨髓间充质干细胞对大鼠心脏移植急性排斥反应的影响

Effects of bone marrow mesenchymal stem cells derived from recipients on acute rejection in rat cardiac transplantation models

摘要:

目的 观察受者同系骨髓间充质干细胞（MSC）对大鼠心脏移植急性排斥反应的影响, 并初步探讨其免疫调节机制。方法 成年雄性Wistar大鼠20只为受体, 随机分为空白对照组和MSC处理组, 每组10只, 行Lewis大鼠→Wistar大鼠颈部心脏移植。空白对照组手术后24 h, 经尾静脉注射3 ml 0.9%氯化钠注射液; MSC处理组手术后24 h, 经尾静脉注射MSC 2×106（悬浮在3 ml 0.9%氯化钠注射液中）。术后1周, 每组随机取4只大鼠, 进行组织学检查及下腔静脉血检测血清白介素（IL）-2及IL-10水平。其余6只用以继续观察移植物存活时间。结果 （1）空白对照组大鼠移植心脏存活（7.2±1.3）d, MSC处理组大鼠移植心脏存活（14.8±2.9）d, 差异显著（P＜0.01）。（2）血清IL-2空白对照组为（233.99±30.19）ng/L, MSC处理组为（249.11±20.34）n g/L, 两组无统计学差异（P＞0.05）; 血清IL-10空白对照组为（81.44±11.01）ng/L, MSC处理组为（158.39±18.70）ng/L, 差异显著（P＜0.01）。（3）病理学分级, 空白对照组3B级1例、4级3例, MSC处理组2级1例、3A级2例、3B级1例, MSC处理组病理分级总体较空白对照组低。结论 静脉注射受者同系骨髓MSC, 可以延长大鼠颈部移植心脏的存活时间, 减轻急性排斥反应的程度。

Abstract:

Objective To investigate the effects of mesenchymal stem cells(MSCs) derived from recipients’ bone marrow on the acute rejection in rat models of cardiac transplantation and to study the possible underlying mechanisms. Methods Twenty Wistar rats bearing transplanted heart from Lewis rats were divided randomly into control group and MSCs treatment group, with 10 in each group. The rats in control group received 3ml 0.9%NaCl solution injection through tail vein at 24h after heart transplantation. The rats in treatment group received 2×106 MSCs suspended in 3ml 0.9%NaCl solution instead. One week after transplantation, 4 rats selected randomly from each group were sacrificed for detection of interleukin(IL)-2 and IL-10 levels in inferior canal vein by ELISA and immunohistolochemical examination. The left 6 rats in each group were used for determination of the grafts survival time. Results The survival time of allografts was (7.2±1.3)d in control group and (14.8±2.9)d in MSCs treatment group respectively(P＜0.01). Serum IL-2 concentration was (233.99±30.19) ng/L in control group and (249.11±20.34) ng/L in MSCs treatment group(P＞0.1). Serum IL-10 concentration was (81.44±11.01) ng/L in control group and (158.39±18.70) ng/L in MSCs treatment group(P＜0.01). In control group, there was 1 case with pathological grade 3B and 3 cases with grade 4. In MSCs group, there was 1 case with grade 2, 2 cases with grade 3A, and 1 case with grade 3B. MSCs treatment group had comparatively lower pathological grade than control group. Conclusion Intravenous infusion of MSCs derived from recipients could prolong the survival time of transplanted heart and reduce the acute rejection.