LPS+TNF-α致休克大鼠胃肠运动及屏障功能的改变

Alterations of gastrointestinal motility and mucosal barrier in shock rat model induced by endotoxin plus TNF α

目的观察内毒素和肿瘤坏死因子（ＴＮＦ）联合致休克模型大鼠胃肠运动功能改变及粘膜损伤的程度．方法采用Ｗｉｓｔａｒ♂大鼠，用内毒素和人重组ＴＮＦα联合致休克模型；将电极埋置在胃、十二指肠、空肠的浆膜面，记录大鼠的胃肠电活动，给大鼠灌胃碳末，测量碳末的推进速度，计数大鼠胃肠电快波频率（Ｆ）、振幅指数（ＡＩ）及碳末推进速度；取制膜后２ｈ的肠系膜淋巴结、心、肝、脾、肺、肾和血进行细菌培养，观察肠道细菌的移位情况；制膜１ｈ后给大鼠灌胃乳果糖／甘露醇混悬液，收集大鼠６ｈ尿液，用高压液相技术测定尿中乳果糖和甘露醇含量，计算它们排出率之比，测定肠粘膜的通透性．用χ２检验比较各组器官细菌感染率的不同，用ｔ检验统计各组间其他各指标的差异，Ｐ＜００５有显著性差异．结果①制模大鼠胃肠运动的改变：模型大鼠胃肠电活动明显抑制，快波的频率［Ｆｒｅ：胃电（１３２±０３０），十二指肠电（４４７±０７６），空肠电（４０７±１２５）次／ｍｉｎ］及振幅指数［ＡＩ：胃电（１３７０±３２３），十二指肠电（４３０６±８００），空肠电（３０７９±７４９）μＶ／ｍｉｎ］明显低于制模前［Ｆｒｅ：胃电（２９１±０１７），十二指肠电?

AIM To study gut motility and mucosal barrier in a shock model induced by endotoxin and recombinant TNF α in rats. METHODS Male Wistar rats weighing 250g - 300g , were intravenously injected with endotoxin plus recombinant human TNF α to lower the systemic arterial pressure. Bipolar electromyograms were recorded from electrodes chronically implanted on the serosa of stomach, duodenum and jejunum, and the frequency and amplitude index of spiking activity were calculated. Oral carbon power was used to observe the function of intestinal propulsion. Two hours after the administration of drugs, mesenteric lymph node, liver, spleen, heart, kidney and blood samples were taken aseptically, and were homogenized in saline, and plated on McConkey's agar for culture at 37℃ for 24 hours. The prevalence of bacteria translocation and the number of bacteria in these tissues were calculated. Concentrations of endothelin, NO, nitric oxide syntheses, motilin, SOD, MDA, diamine oxidase (DAO)activity in blood and DAO in small intestine mucosa were measured. Six-hour urinary excretion of orally administered mannitol and lactulose was measured with high-performance liquid chromatography. RESULTS The gastrointestinal electric activity was inhibited markedly (30 minutes after shock vs before shock; Fre: gastric electric activity 1 32±0 30 vs 2 91±0 17,duodenal 4 47±0 76 vs 17 52±2 43,jejunal 4 07±1 25 vs 22 32±3 35min;AI: gastric 13 70±3 23 vs 26 18±3 45,duodenal 43 06±8 00 vs 158 48±65 92,jejunal 30 79±7 49 vs 149 12± 27 52μV/min and the rate of intestinal propulsion (shock group vs normal group:30 7%±3 6% vs 72 8%±3 92%, P <0 05) was slowed significantly. The damage of epithelial villi of the mucosa, the increased intestinal permeability of lactulose (the rate of the excretion of lactulose and mannitol in shock vs normal rats:12 2±1 2 vs 0 06±0 01, P <0 05),a decrease of diamine oxidase activity (shock rat vs normal rat:0 04±0 04 vs 0 56± 0 04U/g )in gut and the gut bacteria translocation (shock rat vs normal rat:100% vs 0%)showed the impairment of gut barrier function. CONCLUSION The gastrointestinal motility is inhibited and the intestinal permeability is increased in endotoxin and recombinant human tumor necrosis factor α induced shock rats.