白细胞介素-1β和白细胞介素-8在实验性结肠炎发病中的作用及白细胞介素-1受体拮抗剂治疗作用的探讨

来源 :中国医学科学院学报 | 被引量 : 0次 | 上传用户:syfounder
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目的研究白细胞介素1β(IL-1β)和白细胞介素8(IL-8)在结肠炎发病中的作用,观察白细胞介素-1受体拮抗剂(IL-1ra)对结肠炎的疗效。方法用30mg三硝基苯磺酸(TNBS)+0.25ml体积分数为50%乙醇制成大鼠慢性实验性结肠炎模型,然后于不同时间点尾静脉注入7mg/kgIL-1ra,进行实验性治疗,以静脉注入3mg氢化可的松琥珀酸钠作为治疗对照,同时观察治疗前后病变结肠组织学变化,测定结肠髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)活性改变,以原位杂交法观察结肠道组织IL-1β和IL-8mRNA表达水平。结果模型组大鼠结肠组织均出现粘膜下充血、水肿、出血及炎症细胞浸润、粘膜溃疡和隐窝脓肿,以致炎后3d为著,7d后减轻,21d基本恢复正常。模型组二次致炎后上述表现再次出现。整个炎症期均有IL-1βmRNA表达,而IL-8mRNA表达出现于致炎后3d。两种白细胞介素mRNA的表达部位均主要在粘膜固有层和粘膜下层的单核巨噬细胞,但在致炎后3d内,IL-1βmRNA在肠上皮细胞也有表达。IL-1ra治疗后3组大鼠结肠炎症均明显减轻,伴随相应的MPO下降和SOD上升,两种白细胞介素mRNA的表达均未? Objective To investigate the role of interleukin-1β (IL-1β) and interleukin-8 (IL-8) in the pathogenesis of colitis and to investigate the effect of interleukin-1 receptor antagonist (IL-1ra) on colitis. Methods Chronic experimental colitis model was induced in rats by adding 30mg trinitrobenzene sulfonic acid (TNBS) + 0.25ml volume fraction of 50% ethanol, then injecting 7mg / kg IL-1ra intravenously at different time points for experimental treatment , Intravenous infusion of 3mg hydrocortisone sodium succinate as a treatment control, and observed before and after treatment of lesions in the histological changes measured colonic myeloperoxidase (MPO) and superoxide dismutase (SOD) activity changes to the original The hybridization method was used to observe the expression of IL-1β and IL-8 mRNA in colon tissue. Results In the model group, submucosal congestion, edema, hemorrhage, infiltration of inflammatory cells, mucosal ulceration and crypt abscess occurred in the colon tissues of rats in the model group. The rats in the model group were on the 3d after the inflammation, relieved on the 7th day, and returned to normal on the 21st day. The model group after secondary inflammation of the above performance again. IL-1βmRNA expression was observed in the entire inflammatory phase, while IL-8mRNA expression appeared 3d after pro-inflammatory. Both IL-2 mRNA expression sites were mainly in monolayer and submucosal mononuclear macrophages, but IL-1β mRNA was also expressed in intestinal epithelial cells within 3d after pro-inflammatory. IL-1ra treatment of colitis in rats after 3 groups were significantly reduced, accompanied by a corresponding decline in MPO and SOD increased, the two interleukin mRNA expression were not?
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