Affiliated Union Hospital, Fujian Medical University, Fujian, 350001, China.
Exp Biol Med (Maywood). 2013 Jun;238(6):687-95. doi: 10.1177/1535370213490629.
The aim of this study was to preliminarily investigate the effect of bone marrow mesenchymal stem cells (MSCs) on structural change of capillary endothelial barrier and expression variation of aquaporin 1 (AQP1) in kidney at the onset of renal injury caused by severe acute pancreatitis (SAP). Ninety male Sprague-Dawley (SD) rats were divided into the control group, the SAP group in which animals received induction of SAP and the MSCs-treated group in which SAP-induced animals were injected with MSCs. They were further subdivided according to the time point that the animals were killed; 6 h, 12 h and 24 h after the closure of the incision, serum, pancreatic and renal samples were collected, respectively. The level of serum amylase (AMY), creatinine (Cr) and blood urea nitrogen (BUN) were analysed, the change of pancreatic histology was assessed, the structural change of the renal interstitial capillaries was evaluated using the transmission electron microscope (TEM) and the location and expression of AQP1 in kidney were analysed using immunohistochemistry, quantitative polymerase chain reaction and Western blot. The outcomes showed that the level of serum AMY, Cr, BUN elevated, the damage of pancreatic tissue and renal capillary endothelial barrier was aggravated and the expression of AQP1 was reduced significantly after induced pancreatitis. But after treatments with MSCs, the elevation of AMY, Cr and BUN was inhibited, the damage of pancreatic tissue and renal interstitial capillary barrier was alleviated and the down-regulation of AQP1 was reversed. In summary, the MSCs therapy could alleviate renal injury in rats with SAP, the mechanism of which might be related to reduction of the damage to renal interstitial capillary endothelial barrier, and up-expression of AQP1 in kidney.
本研究旨在初步探讨骨髓间充质干细胞(MSCs)对重症急性胰腺炎(SAP)所致肾损伤时毛细血管内皮屏障结构变化和水通道蛋白 1(AQP1)表达变化的影响。90 只雄性 Sprague-Dawley(SD)大鼠分为对照组、SAP 组(接受 SAP 诱导)和 MSCs 治疗组(SAP 诱导后注射 MSCs)。根据处死动物的时间点进一步分为 6 h、12 h 和 24 h 后,分别收集血清、胰腺和肾脏样本。分析血清淀粉酶(AMY)、肌酐(Cr)和血尿素氮(BUN)水平,评估胰腺组织变化,用透射电镜(TEM)评估肾间质毛细血管结构变化,用免疫组织化学、定量聚合酶链反应和 Western blot 分析 AQP1 在肾脏中的定位和表达。结果显示,诱导胰腺炎后,血清 AMY、Cr、BUN 水平升高,胰腺组织和肾毛细血管内皮屏障损伤加重,AQP1 表达明显降低。但经 MSCs 治疗后,AMY、Cr 和 BUN 升高受到抑制,胰腺组织和肾间质毛细血管屏障损伤减轻,AQP1 下调得到逆转。综上所述,MSCs 治疗可减轻 SAP 大鼠的肾损伤,其机制可能与减轻肾间质毛细血管内皮屏障损伤和上调肾脏 AQP1 表达有关。