白介素-1受体拮抗剂对大鼠肠缺血/再灌注损伤的保护作用

Protective effect of interleukin-1 receptor antagonist on intestinal ischemia-reperfusion induced injury in rats

目的探究白介素^(-1)受体拮抗剂(interleukin^(-1) receptor antagonist,IL^(-1)Ra)对大鼠肠缺血/再灌注损伤的保护作用。方法将35只♂SD大鼠随机分为假手术(S)组、模型(I/R)组、不同剂量给药组(C1、C2、C3)。采用夹闭肠系膜上动脉法制备肠缺血/再灌注模型,缺血1 h后松开动脉夹再灌注1 h,给药组于再灌注前15 min尾静脉注射10、20、50mg·kg^(-1)的IL^(-1)Ra。结果缺血/再灌注2 h后,与S组相比,I/R组肠黏膜严重损伤,髓过氧化物酶(myeloperoxidase,MPO)和丙二醛(malondialdehyde,MDA)含量增高,超氧化物歧化酶(superoxide dismutase,SOD)活性降低,肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素^(-1)β(interleukin^(-1)β,IL^(-1)β)、白介素-6(interleukin-6,IL-6)大量释放,差异有显著性。给药组大鼠的肠黏膜病理损伤均明显改善,氧化应激和炎症反应指标有不同程度的改善。结论 IL^(-1)Ra通过缓解氧化应激反应和炎症反应,对肠缺血/再灌注损伤有明显的保护作用,有望用于临床上肠缺血/再灌注损伤的治疗。

Aim To explore the effects of interleukin^（-1） receptor antagonist（ IL^（-1） Ra） on intestinal ischemia-reperfusion（ I/R） induced injury in rats. Methods Thirty-five male SD rats were randomly divided into sham operation group（ S）,model group（ I/R）,different dosage drug groups（ C1,C2,C3）. Rat intestinal I/R model was established via clamping the superior mesenteric artery（ SMA）. After 1 h of ischemia,the arterial clamps were released for 1 h of reperfusion.10,20,50 mg·kg^（-1） of IL-Ra was injected via caudal vein 15 min before reperfusion. Results After 2 h of I/R,compared with S group,I/R group rats exhibited severe damage on the intestinal mucosa,increase in MDA content,decrease in SOD activity,and significant release of TNF-α, IL^（-1）β, IL-6. The results showed that,following the injection of IL^（-1） Ra afterclipping superior mesenteric artery,damage of the intestinal mucosa was obviously relieved in different dosage drug groups. Furthermore,there was different degree of relief on oxidative stress and inflammatory responses. Conclusion IL^（-1） Ra showed obvious protective effect on intestinal I/R induced injury by relieving oxidative stress and inflammatory response,and it may potentially be used in the clinical treatment of intestinal I/R injury.