骨髓间充质干细胞治疗肾缺血再灌注损伤的旁分泌机制

背景：骨髓间充质干细胞已用于肾缺血再灌注损伤修复的实验动物研究。 目的：探讨骨髓间充质干细胞治疗肾缺血再灌注损伤的旁分泌机制。 方法：体外培养、纯化并体外DAPI标记大鼠骨髓间充质干细胞，经下腔静脉移植入肾缺血再灌注损伤模型大鼠体内，观察骨髓间充质干细胞对肾缺血再灌注损伤肾功能的保护作用以及在受体鼠体内的迁移情况，并应用免疫组织化学法检测骨髓间充质干细胞治疗后第2天缺血肾脏组织中血管内皮生长因子、肿瘤坏死因子α细胞因子的表达。 结果与结论：与注射生理盐水的对照组比较，细胞移植组大鼠血清肌酐和尿素氮水平在移植后第1、2天明显降低(P < 0.05)，但细胞移植组移植后第1、2天肾组织中均未见DAPI阳性细胞；第3、4天则逐渐可见DAPI阳性细胞。免疫组织化学染色结果显示，与对照组相比，移植后第2天肾组织中可见较多血管内皮生长因子阳性细胞，而肾组织中肿瘤坏死因子α阳性细胞明显减少。结果显示旁分泌机制参与了骨髓间充质干细胞治疗肾缺血再灌注损伤。

Bone marrow mesenchymal stem cells protect against renal ischemia reperfusion injury through paracrine mechanism

BACKGROUND:Bone marrow mesenchymal stem cells (BMSCs) can be used in the animal experiments of renal ischemia reperfusion injury. OBJECTIVE:To explore the paracrine mechamism of BMSCs in treatment of renal ischemia reperfusion injury. METHODS:Rat BMSCs were isolated by percoll density gradient centrifugation and labeled with 4,6-diamidino-2-pheny-lindole (DAPI). Male SD rats were subjected to clamping renal pedicles for 45 minutes and divided randomly into the transplanted group and the control group. DAPI-labeled MSCs or saline were transplanted into the rats by inferior vena cava. Immunohistochemical method was used to detect the expression of vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) in kidneys day 2 post-operation. RESULTS AND CONCLUSION:Compared with the control group, the serum creatinine and blood urine nitrogen in the transplanted group were significantly decreased at 1 and 2 days after operation (P < 0.05). At 3 days, the DAPI-positive cells could be found in the renal tissue in the transplanted group and significantly increased at 4 days(P < 0.05). The expression of VEGF was increased and the expression of TNF-α was decreased in kidneys in the transplanted group at 2 days by immunohistochemical method. BMSCs can protect against renal ischemia reperfusion injury through the paracrine mechamism.