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Effects of Doxycycline on Intestinal Ischemia Reperfusion Injury Induced by Abdominal Compartment Syndrome in a Rat Model

机译:强力霉素对大鼠腹部隔室综合征所致肠缺血再灌注损伤的影响

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BACKGROUND: Abdominal compartment syndrome (ACS) refers to organ dysfunction and ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut results in the triggering of a systemic inflammatory response by releasing cytokines which, in turn, causes capillary leakage leading to bowel edema, further increasing intra-abdominal pressure and resulting in a morbid cycle of ischemia and edema.OBJECTIVE: The aim of this study was to determine the effects of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of ACS.METHODS: Sprague-Dawley rats were divided into 5 equal groups. In groups 1 and 2, saline (1 cc IP) was administered during induction of ACS and intestinal samples were removed at 1 and 24 hours, respectively, after decompression. In groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS and, similarly, intestinal samples were removed at 1 and 24 hours after decompression. In the control group (group 5), intestinal samples were collected without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-a, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 were studied and the apoptotic cells were enumerated histopathologically. Apoptosis and beta-cell lymphoma 2 (pcl-2) expression were assessed immunohistochemically.RESULTS: Thirty-five rats were evenly divided into 5 groups of 7 rats each. MDA, IL-1beta, IL-6, TNF-alpha, and MMP-2 levels were significantly higher in group 1 one hour after the reperfusion period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P < 0.001, and P < 0.01, respectively). The same parameters were significantly lower in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05). The mean (SD) number of apoptotic cells and the expression of Pcl-2 was highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9 [5.0], respectively) and significantly greater than that in group 4 (P < 0.001 and P < 0.05, respectively).CONCLUSION: Doxycycline was associated with protective effects against I/R injury through decreasing apoptosis via attenuating the response of proinflammatory cytokines and inhibiting the activity of MMP-2 in this rat model.
机译:背景:腹腔室综合征(ACS)是指由腹内高压(IAH)引起的器官功能障碍和局部缺血。肠缺血可通过释放细胞因子触发全身性炎症反应,进而引起毛细血管渗漏,导致肠水肿,进一步增加腹腔内压力,并导致缺血和水肿的病态循环。本研究的目的是确定强力霉素对ACS大鼠模型的肠缺血再灌注(I / R)损伤的影响。方法:将Sprague-Dawley大鼠分为5组,每组相等。在第1组和第2组中,在ACS诱导过程中给予生理盐水(1 cc IP),减压后分别在1和24小时取出肠样品。在第3组和第4组中,在ACS诱导过程中注射强力霉素(10 mg / kg IP),并且相似地,减压后1和24小时取出肠样品。在对照组(第5组)中,收集肠样品而不诱导ACS。研究了丙二醛(MDA),白介素(IL)-1beta,IL-6,肿瘤坏死因子(TNF)-a,基质金属蛋白酶2(MMP-2)和金属蛋白酶-1的组织抑制剂,并研究了凋亡细胞进行了组织病理学计数。结果:将35只大鼠平均分为5组,每组7只。每组5只,每组7只。再灌注后1小时,第1组的MDA,IL-1beta,IL-6,TNF-α和MMP-2水平明显高于对照组(P <0.001,P <0.001,P <0.05,P <0.001和P <0.01)。施用强力霉素的第3组的相同参数明显低于第1组(分别为P <0.001,P <0.05,P <0.05,P <0.001和P <0.01)。但是,第2组和第4组之间在第24小时之间没有显着差异(全部,P> 0.05)。再灌注后24小时,第2组中凋亡细胞的平均数(SD)和Pcl-2的表达最高(分别为92.5 [11.4]和35.9 [5.0]),并显着高于第4组(结论:强力霉素可通过减轻促炎细胞因子的应答并抑制MMP-2的活性来减少细胞凋亡,从而具有抗I / R损伤的作用。

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