Inflammation of the rat prostate evokes release of macrophage migration inhibitory factor in the bladder: Evidence for a viscerovisceral reflex
Inflammation of the rat prostate evokes release of macrophage migration inhibitory factor in the bladder: Evidence for a viscerovisceral reflex
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DOI：
10.1097/01.ju.0000138055.01611.13
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发表时间：
2004-12-01
影响因子：
6.6
通讯作者：
Meyer-Siegler, KL
中科院分区：
文献类型：
--
作者：
Vera, PL;Meyer-Siegler, KL
目的：巨噬细胞迁移抑制因子（MIF）是一种促炎细胞因子，存在于膀胱上皮的预先形成的储存中。我们检查了前列腺炎症对排尿频率、膀胱组织学和膀胱 MIF 含量的影响，作为研究介导盆腔内脏炎症的内脏内脏反射的模型。材料和方法：在聚氨酯麻醉的雄性大鼠中进行膀胱测压。将福尔马林或盐水注射到前列腺腹叶以诱发炎症。注射后1小时继续进行膀胱测量。然后切除膀胱、前列腺腹叶和腰骶脊髓，检测MIF、环氧合酶-2（COX-2）和神经生长因子（NGF）的蛋白水平和基因表达。对膀胱和前列腺的水肿进行组织学验证。结果：前列腺内注射福尔马林几乎立即产生膀胱反射亢进，并在观察期间维持这种反射亢进。组织学检查时发现膀胱水肿。前列腺注射后，膀胱MIF蛋白量减少，而COX-2和NGF增加。膀胱MIF、COX-2和NGF mRNA增加。在接受前列腺内福尔马林的动物中，所有检查因素的腰骶脊髓蛋白质和 mRNA 量均增加。颈髓未观察到任何变化。注射与染料混合的福尔马林的大鼠显示染料对前列腺的限制。结论：大鼠的内脏反射可能由腰骶脊髓介导，产生膀胱反射亢进和膀胱水肿，并引起膀胱中的MIF释放和其他炎症介质的诱导。这支持了我们的假设，即 MIF 参与盆腔内脏的神经源性炎症，并且它可能代表一个有趣的治疗靶点。
Purpose: Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is found in preformed stores in bladder epithelium. We examined the effects of prostatic inflammation on micturition frequency, bladder histology and bladder MIF content as a model in which to study viscerovisceral reflexes mediating pelvic visceral inflammation.Materials and Methods: Cystometry was performed in urethane anesthetized male rats. Formalin or saline was injected into the ventral lobe of the prostate to induce inflammation. Cystometry continued 1 hour after injection. The bladder, ventral lobes of the prostates and lumbosacral spinal cord were then removed, and protein levels and gene expression of MIF, cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) were examined. Edema was verified histologically in the bladder and prostate.Results: Intraprostatic formalin produced almost immediate bladder hyperreflexia, which was maintained during the observation period. Bladder edema was noted during histological examination. Bladder MIF protein amounts decreased, while COX-2 and NGF increased after prostatic injection. Bladder MIF, COX-2 and NGF mRNA increased. In the lumbosacral spinal cord protein and mRNA amounts increased for all factors examined in animals that received intra-prostatic formalin. No changes were observed in the cervical cord. Rats injected with formalin mixed with dye showed restriction of the dye to the prostate.Conclusions: A viscerovisceral reflex in the rat, probably mediated by the lumbosacral spinal cord, produced bladder hyperreflexia and bladder edema, and evoked MIF release from the bladder and the induction of other inflammatory mediators. This supports our hypothesis that MIF is involved in neurogenic inflammation in the pelvic viscera and it may represent an interesting therapeutic target.