Yang Hui, Jin Yu, Wang Chun H, Tang Cheng W
Department of Gastroentrology, Nanjing Children's Hospital, Nanjing Medical University, 210008, China.
Regul Pept. 2013 Sep 10;186:36-42. doi: 10.1016/j.regpep.2013.06.014. Epub 2013 Jul 16.
Mesenteric lymph pathway serves as the primary route by which gut injury leads to systemic inflammation and distant organ injury. The inflammation of the intestinal tract is partially mediated by vasoactive intestinal peptide (VIP). Therefore, the aim of this study was to test whether exogenous VIP affects mesenteric lymph pathway during early intestinal ischemia-reperfusion (IIR) injury. Rats were randomized into control, control+VIP, IIR and IIR+VIP groups. The observation of mesenteric lymph flow was carried out by cannulation of mesenteric lymphatics. The distribution of in vivo lymphocyte trafficking was performed by (51)Cr labeled lymphocytes and was measured by γ-counter. Endotoxin concentration was assayed using the limulus test kit and TNF-α level was detected by ELISA. When IIR injury treated with VIP, the volumes of lymph flow increased by 80%, which caused the number of lymphocytes exiting in mesenteric lymphatic increased by 50% while the proportion of (51)Cr-lymphocytes in Peyer's patches, intestinal effector tissues, mesenteric nodes, large intestine, stomach decreased by 58%, 51%, 58%, 63%, 64% respectively at the 6th h after reperfusion following intestinal ischemia. Meanwhile, endotoxin and TNF-α levels in intestinal lymph decreased by 51% and 83%. These results suggest that exogenous VIP ameliorates IIR induced splanchnic organ damage via inhibition of toxic mediators reaching systemic circulation and reinforcement of the effective immune responses in gut-associated lymphoid tissues (GALT).
肠系膜淋巴途径是肠道损伤导致全身炎症和远处器官损伤的主要途径。肠道炎症部分由血管活性肠肽(VIP)介导。因此,本研究的目的是测试外源性VIP在早期肠道缺血再灌注(IIR)损伤期间是否影响肠系膜淋巴途径。将大鼠随机分为对照组、对照组+VIP组、IIR组和IIR+VIP组。通过肠系膜淋巴管插管观察肠系膜淋巴流量。采用(51)Cr标记淋巴细胞进行体内淋巴细胞转运分布,并通过γ计数器进行测量。使用鲎试剂检测内毒素浓度,通过ELISA检测TNF-α水平。当用VIP治疗IIR损伤时,淋巴流量增加80%,导致肠系膜淋巴中流出的淋巴细胞数量增加50%,而在肠道缺血再灌注后第6小时,派尔集合淋巴结、肠道效应组织、肠系膜淋巴结、大肠、胃中(51)Cr标记淋巴细胞的比例分别下降58%、51%、58%、63%、64%。同时,肠道淋巴中的内毒素和TNF-α水平分别下降51%和83%。这些结果表明,外源性VIP通过抑制有毒介质进入体循环和增强肠道相关淋巴组织(GALT)中的有效免疫反应,改善IIR诱导的内脏器官损伤。