Effects of trapidil on intestinal mucosal barrier function and bacterial translocation after intestinal ischemia and reperfusion in an experimental rat model
Effects of trapidil on intestinal mucosal barrier function and bacterial translocation after intestinal ischemia and reperfusion in an experimental rat model
复制标题
DOI：
10.1016/s0011-393x(03)00091-2
复制
发表时间：
2003-06-01
影响因子：
1.9
通讯作者：
Aydin, S
中科院分区：
文献类型：
--
作者：
Colak, T;Ozturk, C;Aydin, S
背景资料：肠缺血和再灌注可能是粘膜屏障损伤、细胞因子表达和细菌移位（BT）的主要触发因素。曲匹地尔是一种磷酸二酯酶和血小板源性生长因子抑制剂，可减少脂质过氧化和抑制细胞因子的产生。目的：本研究的目的是通过检测曲匹地尔对实验性缺血/再灌注（I/R）大鼠模型肠屏障功能的影响，评估曲匹地尔是否可能通过抑制脂质过氧化和促炎细胞因子来保护肠上皮屏障。曲匹地尔用于肠缺血40分钟再灌注12小时引起的肠屏障功能障碍的大鼠模型。为此，将大鼠随机分为4个治疗组之一，如下：（1）假手术和盐水给药（1 mL IV）（2）假手术组和曲匹地尔组（3）I/R和生理盐水给药（ImL IV）（I/R组）;和（4）I/R和曲匹地尔给药（8 mg/kg IV）（I/R+T组）。肠屏障功能进行了评估，通过组织病理学检查，血液丙二醛（MDA）水平，和BT。结果：I/R+T组表现出显着减少BT的发病率与I/R组相比，在肝脏和肠系膜淋巴结，肝脏，脾脏，腹膜易位细菌的中位数菌落计数与I/R组相比。此外，平均血液MDA水平表明，脂质过氧化作用在I/R+T组与I/R组相比，显着降低。病理学结果显示，再灌注前曲匹地尔管理保存肠粘膜的完整性和抑制炎症细胞浸润到intestin.Conclusions：在这项实验研究中，相关性似乎存在肠屏障功能障碍和BT之间。肠道屏障功能障碍可能会使大量细菌从肠道进入远处器官。曲匹地尔治疗可能通过抑制血栓素A（2）、脂质过氧化、促炎细胞因子和刺激的前列环素来保护肠屏障，从而抑制BT。未来的剂量和时间依赖性研究将有助于揭示曲匹地尔对BT的影响。版权所有（C）2003 Excerpta Medica，Inc.
Background: Intestinal ischemia and reperfusion may be the primary triggers of mucosal barrier impairment, cytokine expression, and bacterial translocation (BT). Trapidil is a phosphodiesterase and platelet-derived growth factor inhibitor that reduces lipid peroxidation and inhibits the production of cytokines.Objective: The goal of this study was to assess whether trapidil might protect the intestinal epithelial barrier by inhibiting lipid peroxidation and proinflammatory cytokines by testing the effect of trapidil on intestinal barrier function in an experimental ischemia/reperfusion (I/R) rat model.Methods: Trapidil was used in a rat model of intestinal barrier dysfunction caused by intestinal ischemia for 40 minutes followed by reperfusion for 12 hours. To do this, the rats were randomized to 1 of 4 treatment groups, as follows: (1) sham surgery and saline administration (1 mL IV) (Sham group); (2) sham surgery and trapidil administration (8 mg/kg IV) (Sham+T group); (3) I/R and saline administration (1 mL IV) (I/R group); and (4) I/R and trapidil administration (8 mg/kg IV) (I/R+T group). Intestinal barrier function was assessed by histopathologic examination, blood malondialdehyde (MDA) level, and BT.Results: The I/R+T group showed significantly less incidence of BT compared with the I/R group in the liver and reduced median colony count of translocated bacteria in mesenteric lymph nodes, liver, spleen, and peritoneum compared with the I/R group. Furthermore, the mean blood MDA level demonstrated that lipid peroxidation was significantly decreased in the I/R+T group compared with the I/R group. Histopathologic findings revealed that trapidil administration before reperfusion preserved intestinal mucosal integrity and inhibited the infiltration of inflammatory cells into the intestines.Conclusions: In this experimental study, a correlation seemed to exist between intestinal barrier dysfunction and BT. Intestinal barrier dysfunction may allow a large amount of bacteria to pass from the gut to distant organs. Trapidil treatment may inhibit BT by preserving intestinal barrier by inhibiting thromboxane A(2), lipid peroxidation, proinflammatory cytokines, and stimulated prostacyclin. Future dose- and time-dependent studies will be helpful in revealing the effects of trapidil on BT. Copyright (C) 2003 Excerpta Medica, Inc.