Department of Physiology, Faculty of Medicine, Adnan Menderes University, Aydin 09100, Turkey.
Dig Dis Sci. 2010 Feb;55(2):245-52. doi: 10.1007/s10620-009-0737-0. Epub 2009 Feb 20.
The aim of this study was to investigate the possible protective effects of leflunomide, which has antioxidant and anti-inflammatory properties, against intestinal IR injury in rats.
Forty female Wistar albino rats were divided into six groups: control (n = 5), drug control (n = 7), sham operated (n = 7), IR alone (n = 7), IR plus vehicle (IR + vehicle, n = 7) and IR plus 20 mg/kg leflunomide (IR + Leflunomide, n = 7). While rats were pretreated intragastrically with leflunomide (20 mg/kg) and vehicle in three doses prior to the experiment, respectively, in the IR + Leflunomide and IR + vehicle groups, no additional application was done in the IR alone group. Intestines were exteriorized, and the superior mesenteric artery was occluded for 45 min ischemia, and then the clamp was removed for 120 min reperfusion. After the experiment, the intestines were removed for biochemical and histological examinations. Additionally, blood samples were taken for measurements of antioxidant parameters.
The intestinal IR significantly increased the MDA level and MPO activity; however, treatment with leflunomide reversed those findings (P < 0.05). The CAT activity of the IR + Leflunomide group was significantly higher than in the IR groups (P < 0.05). The SOD activity was increased in the intestinal IR group, and leflunomide treatment reversed that, too (P <0.05). The light microscopic findings showed that IR caused mucosal necrosis and leflunomide treatment reduced the morphological alterations associated with IR (P < 0.05).
Intestinal IR injury may be reversed by the anti-inflammatory and antioxidant actions of leflunomide.
本研究旨在探讨具有抗氧化和抗炎特性的来氟米特对大鼠肠道缺血再灌注 (IR) 损伤的可能保护作用。
将 40 只雌性 Wistar 白化大鼠分为六组:对照组 (n = 5)、药物对照组 (n = 7)、假手术组 (n = 7)、IR 组 (n = 7)、IR 加载体组 (IR + 载体组,n = 7) 和 IR 加 20mg/kg 来氟米特组 (IR + 来氟米特组,n = 7)。在实验前,分别用来氟米特 (20mg/kg) 和载体对 IR + 来氟米特和 IR + 载体组中的大鼠进行 3 次胃内预处理,而在 IR 组中不进行额外的应用。将肠系膜上动脉夹闭 45 分钟以造成肠道缺血,然后松开夹闭恢复再灌注 120 分钟。实验结束后,取出肠道进行生化和组织学检查。此外,采集血液样本以测量抗氧化参数。
肠道 IR 显著增加 MDA 水平和 MPO 活性;然而,来氟米特治疗逆转了这些发现 (P < 0.05)。IR + 来氟米特组的 CAT 活性明显高于 IR 组 (P < 0.05)。IR 组的 SOD 活性增加,来氟米特治疗也逆转了这一现象 (P < 0.05)。光镜检查结果显示,IR 导致黏膜坏死,来氟米特治疗减轻了与 IR 相关的形态改变 (P < 0.05)。
来氟米特的抗炎和抗氧化作用可能逆转肠道 IR 损伤。