Colak Tahsin, Ozturk Candan, Polat Ayse, Bagdatoglu Ozlen, Kanik Arzu, Turkmenoglu Ozgur, Aydin Suha
General Surgery.
Microbiology.
Curr Ther Res Clin Exp. 2003 Jun;64(6):355-66. doi: 10.1016/S0011-393X(03)00091-2.
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.
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.
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.
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.
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 A2, lipid peroxidation, proinflammatory cytokines, and stimulated prostacyclin. Future dose- and time-dependent studies will be helpful in revealing the effects of trapidil on BT.
肠道缺血再灌注可能是黏膜屏障受损、细胞因子表达和细菌易位（BT）的主要触发因素。曲匹地尔是一种磷酸二酯酶和血小板衍生生长因子抑制剂，可减少脂质过氧化并抑制细胞因子的产生。
本研究的目的是通过在实验性缺血/再灌注（I/R）大鼠模型中测试曲匹地尔对肠道屏障功能的影响，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道上皮屏障。
曲匹地尔用于肠道缺血40分钟后再灌注12小时所致肠道屏障功能障碍大鼠模型。为此，将大鼠随机分为4个治疗组中的1组，如下：（1）假手术并静脉注射生理盐水（1 mL）（假手术组）；（2）假手术并静脉注射曲匹地尔（8 mg/kg）（假手术+曲匹地尔组）；（3）I/R并静脉注射生理盐水（1 mL）（I/R组）；（4）I/R并静脉注射曲匹地尔（8 mg/kg）（I/R+曲匹地尔组）。通过组织病理学检查、血液丙二醛（MDA）水平和细菌易位评估肠道屏障功能。
与I/R组相比，I/R+曲匹地尔组肝脏中细菌易位的发生率显著降低，肠系膜淋巴结、肝脏、脾脏和腹膜中转位细菌的中位菌落数也低于I/R组。此外，平均血液MDA水平表明，与I/R组相比，I/R+曲匹地尔组脂质过氧化显著降低。组织病理学结果显示，再灌注前给予曲匹地尔可保持肠道黏膜完整性，并抑制炎症细胞向肠道浸润。
在本实验研究中，肠道屏障功能障碍与细菌易位之间似乎存在相关性。肠道屏障功能障碍可能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A2、脂质过氧化、促炎细胞因子和刺激前列环素产生来维持肠道屏障，从而抑制细菌易位。未来的剂量和时间依赖性研究将有助于揭示曲匹地尔对细菌易位的影响。
