Lu Fengchun, Wang Feng, Chen Zhiyao, Huang Heguang
General Surgery Department, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
Stem Cell Res Ther. 2017 Jan 23;8(1):12. doi: 10.1186/s13287-017-0471-z.
Acute necrotizing pancreatitis (ANP) is often complicated by multiple organ failure. The small intestine is frequently damaged during ANP. Capillary leakage in multiple organs during ANP is one of the most important causes of multiple organ dysfunction. Damage to the capillary endothelial barrier and impaired water transportation could lead to capillary leakage in ANP.
Sprague-Dawley (SD) rats were randomized into a control group, the ANP group, the culture media-treated group, or the bone marrow-derived mesenchymal stem cell (BMSC)-treated group (30 rats in each group). Ten rats in each group were sacrificed at 6, 12, and 24 h after induction of experimental models. Serum, ascites, pancreatic, and small intestinal samples were collected. The levels of serum and ascites albumin and amylases were measured, pancreatic histology was assessed, and the connection changes between vessel endothelial cells were evaluated using scanning electron microscopy (SEM). Capillary leakage in small intestinal tissue was observed visually by tracking fluorescein isothiocyanate (FITC)-albumin, and was measured by the Evans blue extravasation method. The location and expression of aquaporin 1 (AQP1) in the small intestine was analyzed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blot.
The outcomes showed that the level of serum and ascites amylase is elevated. Conversely, the level of serum albumin is decreased while ascites albumin is elevated. There is damage to pancreatic tissue, and the small intestinal capillary endothelial barrier was aggravated. Furthermore, the expression of AQP1 was reduced significantly after induced ANP. Following treatment with MSCs, the elevation of amylase and the decrease of serum albumin were inhibited, the damage to pancreatic tissue and the level of small intestinal capillary leakage was alleviated, and the downregulation of AQP1 was reversed.
In conclusion, MSC therapy could alleviate small intestinal injury in rats with ANP, the mechanism of which might be related to reduction of damage to the small intestinal capillary endothelial barrier, and increased expression of AQP1 in the small intestine.
急性坏死性胰腺炎(ANP)常并发多器官功能衰竭。在ANP期间小肠常受到损伤。ANP期间多器官的毛细血管渗漏是多器官功能障碍的最重要原因之一。ANP中毛细血管内皮屏障受损和水运输受损可导致毛细血管渗漏。
将Sprague-Dawley(SD)大鼠随机分为对照组、ANP组、培养基处理组或骨髓间充质干细胞(BMSC)处理组(每组30只大鼠)。在诱导实验模型后6、12和24小时处死每组中的10只大鼠。收集血清、腹水、胰腺和小肠样本。测量血清和腹水白蛋白及淀粉酶水平,评估胰腺组织学,并使用扫描电子显微镜(SEM)评估血管内皮细胞之间的连接变化。通过追踪异硫氰酸荧光素(FITC)-白蛋白肉眼观察小肠组织中的毛细血管渗漏,并通过伊文思蓝外渗法进行测量。使用免疫组织化学、实时聚合酶链反应(PCR)和蛋白质印迹分析水通道蛋白1(AQP1)在小肠中的定位和表达。
结果显示血清和腹水淀粉酶水平升高。相反,血清白蛋白水平降低而腹水白蛋白水平升高。胰腺组织有损伤,小肠毛细血管内皮屏障加重。此外,诱导ANP后AQP1的表达显著降低。用间充质干细胞治疗后,淀粉酶的升高和血清白蛋白的降低受到抑制,胰腺组织损伤和小肠毛细血管渗漏水平得到缓解,AQP1的下调得到逆转。
总之,间充质干细胞治疗可减轻ANP大鼠的小肠损伤,其机制可能与减少小肠毛细血管内皮屏障损伤及增加小肠中AQP1的表达有关。