肠血管活性多肽或生长抑素对多器官功能障碍综合征鼠肠黏膜MAdCAM-1表达的影响

Effects of vasoactive intestinal peptide or sonmtostatin on the expression of MADCAM-1 in the intestinal mucosa of rats with multiple organ dysfunction syndrome

目的探讨肠血管活性多肽（VIP）或生长抑素（SST）对多器官功能障碍综合征（MODS）大鼠小肠黏膜地址素黏附分子-1（MAdCAM-1）表达的影响及其对MODS防治的意义。方法36只雄性Wistar大鼠随机分为6组（每组6只），包括对照组（正常大鼠）、VIPI组和SST1组（分别经VIP和SST处置的正常大鼠）、MODS组（MODS大鼠）、VIP2组和SST2组（分别经VIP和SST处置的MODS大鼠）。采用肠缺血再灌注方法制作MODS大鼠（出现全身炎症反应，〉2个器官功能障碍）模型。VIP或SST以0．2ρmol·g^-1·h^-1静脉输入和0．25ρmol／g腹腔注入大鼠体内。各组收集的肠淋巴细胞用^51Cr标记后回输入大鼠体内，γ计数器测定其在肠相关淋巴组织（GALT）的数量分布；Western blot测定各组小肠黏膜MAdCAM-1的表达；组织化学法观察各组小肠黏膜组织学变化。数据采用t检验进行分析。结果VIP1组和SST1组小肠弥散淋巴组织MAdCAM-1表达的峰浓度值分别为（157．67±2．52）、（154．33±3．22），Peyer＇s结为（136．00±1．00）、（137．00±1．00），较对照组[（165．33±1．53）、（152．67±2．31）]无显著改变（P〉0．05）；归巢至小肠弥散淋巴组织^51Cr-细胞量占总^51Cr-细胞量的1．04％±0．59％、1．01％±0．83％，较对照组（1．07％±0．61％）无显著改变（P〉0．05）；Peyer＇s结为1．83％±0．90％、1．56％±0．64％，显著低于MODS组[（3．85％±2．02％），P〈0．05]。VIP2组和SST2组小肠弥散淋巴组织MAdCAM-1表达的峰浓度值分别为（158．00±2．65）、（154．33±1．53），Peyer＇s结为（156．33±1．53）、（151．33±2．31），较MODS组[（175．33±2．52）、（173．00±2．65），P〈0．05]；归巢至小肠弥散淋巴组织^51Cr-细胞量占总^51Cr-细胞量的1．58％±0．42％、1．45％±0．26％，Peyer＇s结为2．14％±1．49％、0．81％±0．35％，显著低于MODS组[（3．23％±1．69％）、（5．04％±1．23％），P〈0．05]，并伴有肠黏膜组织学损害的减轻。结论增加MODS大鼠血循环中的VIP或SST，可通过抑制肠黏膜MAdCAM-1表达，减少肠淋巴细胞归巢至GALT，减轻MODS时肠黏膜的炎性损伤。

Objective To investigate the effects of somatostatin （SST） or vasoactive intestinal peptide （VIP）on the expression of MAdCAM-1 in the intestinal mucosa of rats with multiple organ dysfunction syndrome （MODS） and its significance of prevention and treatment of MODS. Method Thirty six Wistar male rats were randomly divided into 6 groups （6 rats in each group）, including control group,VIP group 1 and SST groupl （rats treated with VIP and SST respectively）, MODS group （rats with MODS）, VIP group 2 and ssr group 2（MODS rats treated with VIP and SST respectively）. The rat model of MODS （system inflammnatory response syndrome, 〉 2 organs dysfunction） was established by occlusion of superior mesenteric arteries. 0.2 ρmol·g^-1· h^-1 VIP or SST by intravenous injection combined with 0.25 ρmol/g VIP or SST by intraperitoneal injection were injected into rats. In each group, intestinal lymphocytes from rats labeled with ^51Cr were infused into rat veins and were quantified with γcounter in GALT. The expression of MAdCAM-1 in the intestinal mucosa was measured by western blot. Inflammation in the intestinal mucosa was evaluated with histological sections. Student＇s t test was used to assess difference between the experiment group and the control group. Results In VIP group 1 and SST group 1, the peak values of MAdCAM-1 expression in diffusive lymphatic tissue of small intestinal were 157.67 ± 2.52 and 154.33 ± 3.22, and those in Peyer patches were 136.00 ± 1.00 and 137.00 ± 1.00. There were no significant difference when compared with control group （165.33 ± 1.53, 152.67 ± 2.31, P 〉 0.05 ）. The percentage of ^51Cr-lymphocytes in diffusive lymphatic tissue of small intestine（ 1.04% ± 0.59%, 1.01% ± 0.83%） showed no significant difference from control group （1.07% ± 0.61%, P 〉 0.05）, and those in Peyer patches （1.83% ± 0.90%, 1.56% ± 0.64% ） were significantly less than control group （3.85% ± 2.02%, P 〈 0.05）. In VIP group 2 and SST group 2, the peak values of MAdCAM-1 expression in diffusive lymphatic tissue of small intestinal （ 158.00 ± 2.65,154.33± 1.53） and Peyer patches （156.33 ± 1.53, 151.33 ± 2.31） were significantly less than MODS group （175.33 ± 2.52, 173.00 ± 2.65, P 〈 0.05）. The percentage of ^51Cr-lymphocytes in diffusive lymphatic tissue of small intestine （ 1.58 % ± 0. 42 %, 1.45 % ± 0. 26 % ） and Peyer patches （2. 14 % ± 1.49 %, 0. 81% ± 0.35%） were significantly less than MODS group （3.23% ± 1.69%, 5.04% ± 1.23%, P 〈0.05） and the severe histopathological damage in intestine was relieved. Conclusions VIP or SST reduced intestinal lymphocytes homing to GALT in rats with MODS through suppressing the expression of MAdCAM-1, and attenuated the inflammatory injure in the intestinal mucosa.