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移动抑制因子介导脊髓蛛网膜下腔注射半抗原诱发的大鼠结肠炎

吴星宇, 潘慧, 梅林

北京大学医学部生理学与病理生理学系.北京 100083

摘要

近年来有观点认为溃疡性结肠炎(ulcerative colitis, UC)是一种神经源性炎症。作者实验室不久前报道，以脊髓蛛网膜下腔(intrathecal, ith)注射半抗原二硝基氯苯(2,4--dinitrochlorobenzene, DNCB)的方法，在致敏大鼠建立了结肠炎模型。该研究拟进一步探讨此结肠炎过程中神经免疫介导物移动抑制因子(migration inhibitory factor, MIF)是否参与其发病机制。选用7---9周龄健康雄性Sprague--Dawley大鼠，用免疫荧光双染法分别测定ith注射DNCB后肠壁神经组织和脊髓组织MIF蛋白的表达。以MIF抗体ith预处理方法，观察对ith注射DNCB后大鼠的疾病活动指数(disease active index, DAI)评分和结肠组织病理变化的影响。结果表明：ith DNCB组大鼠的结肠神经组织和脊髓组织MIF蛋白的荧光强度显著高于ith 乙醇(对照)组；MIF抗体(1:10，1:5)预处理能够显著减轻由ith 注射DNCB引起的DAI高评分和结肠病理变化。上述结果提示，肠和脊髓神经组织MIF活性升高或/和释放增多是ith注射DNCB后结肠炎发生的一个重要原因，神经免疫机制参与了ith注射DNCB引起的大鼠结肠炎过程。

关键词： 结肠炎; 移动抑制因子; 脊髓蛛网膜下腔注射; 二硝基氯苯; 大鼠

Migration inhibitory factor is involved in experimental colitis induced by intrathecal injection of haptten to rat

Wu Xingyu, Pan Hui, Mei Lin

Department of Physiology and Pathophysiology,Peking University Health Science Center.Beijing 100083

Abstract

In recent years, there has emerged academic tendency towards the neurogenic mechanism of ulcerative colitis (UC). As one of the supporting to the hypothesis of UC being a neurogenic inflammation, we have built a colitis model by intrathecal (ith) injection of a haptten 2,4-dinitrochlorobenzene (DNCB) to DNCB sensitized rats. In order to explore further the neuroimmune mechanism of this colitis model, we here focused on a pro-inflammatory cytokine, migration inhibitory factor (MIF), to observe its expression in rat colon nervous tissue and spinal cord in the colitis induced by ith injection of DNCB. At the same time we also observed the effect of MIF antibody pretreatment on the disease active index (DAI) score and the colon pathology of HE staining in the colitis rats. The results obtained showed that the immunofluorescence staining of MIF protein in colon nervous tissue and spinal cord were increased in 0.8% and 1.6% DNCB-induced colitis groups than that in the control (60% ethanol) group. Both the colon pathology and the DAI score were significantly reduced by MIF antibody ith pretreatment. Ith injection of 0.8% DNCB after MIF antibody (1:10, 1:5) pretreatments could only induce lower DAI score (P<0.01 as compared, respectively, to the IgG pretreatment group). The colon pathological changes in ith 0.8% DNCB rats were mild, even little after MIF antibody (1:10, 1:5) pretreatments. These results suggest that MIF in spinal cord and enteric nervous system is possibly involved in the rat colitis induced by ith injection of DNCB, which reflects a neuroimmune mechanism underlying this kind of colitis. MIF is possibly one of the important neurochemical factors in this experimental colitis, even in the UC.

Key words: colitis;migration inhibitory factor;Intrathecal injection;dinitrochlorobenzene;rat

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引用本文：

吴星宇, 潘慧, 梅林. 移动抑制因子介导脊髓蛛网膜下腔注射半抗原诱发的大鼠结肠炎[J]. 生理学报 2008; 60 (3): 419-424.

Wu Xingyu, Pan Hui, Mei Lin. Migration inhibitory factor is involved in experimental colitis induced by intrathecal injection of haptten to rat. Acta Physiol Sin 2008; 60 (3): 419-424 (in Chinese with English abstract).