Neural control of substance P induced up-regulation and release of macrophage migration inhibitory factor in the rat bladder.
Neural control of substance P induced up-regulation and release of macrophage migration inhibitory factor in the rat bladder.
复制标题
P物质的神经控制诱导大鼠膀胱中巨噬细胞迁移抑制因子的上调和释放。
DOI：
10.1016/j.juro.2008.02.040
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Meyer-Siegler,KatherineL
中科院分区：
文献类型：
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作者：
Vera,PedroL;Wang,Xihai;Meyer-Siegler,KatherineL
目的观察实验性炎症后腔内液中巨噬细胞迁移抑制因子的升高及其对膀胱的促炎作用。我们研究了神经活动和特定神经递质系统对炎症期间巨噬细胞迁移抑制因子从膀胱释放的机制的贡献。材料与方法对Sprague-Dawley大鼠进行麻醉。排空膀胱并注入生理盐水。老鼠收到生理盐水作为对照(0.1毫升/ 100克体重)或P物质(σ®)(40μg / kg放入盐水中,0.1 ml / 100通用体重)皮下注射以及六甲铵(σ)(50毫克/公斤)在生理盐水腹腔内(0.1 ml / 100克体重),利多卡因(2%,0.3毫升)膀胱内的,阿托品(σ)(3毫克/公斤盐,0.1 ml / 100克体重)静脉注射,心得安(σ)(3毫克/公斤盐,0.1 ml / 100克体重)静脉注射或酚妥拉明(σ)(10毫克/公斤盐,0.1 ml/100克体重)静脉注射。1小时后，取出膀胱内积液，切除膀胱。采用酶联免疫吸附法和Western blotting检测腹腔内液中巨噬细胞迁移抑制因子水平。用逆转录-聚合酶链反应检测膀胱匀浆中mif的表达。结果静脉注射利多卡因或六甲溴铵阻断神经节可阻止P物质诱导的巨噬细胞迁移抑制因子的释放。此外，阿托品和酚妥拉明预处理对巨噬细胞迁移抑制因子的释放也有抑制作用，而心得安没有作用。P物质治疗增加了膀胱内的emifup调节，但只能通过膀胱内利多卡因来阻止。结论P物质诱导膀胱巨噬细胞迁移抑制因子释放是通过神经激活介导的。节后副交感神经（通过毒蕈碱受体）和交感神经（通过α-肾上腺素能受体）纤维介导巨噬细胞迁移抑制因子释放，而激活膀胱传入神经末梢上调mif。
PurposeMacrophage migration inhibitory factor is increased in intraluminal fluid after experimental inflammation and it mediates proinflammatory effects on the bladder. We examined the contribution of nerve activity and specific neurotransmitter systems to the mechanism of macrophage migration inhibitory factor release from the bladder during inflammation.Materials and MethodsMale Sprague-Dawley rats were anesthetized. The bladders were emptied and filled with saline. Rats received saline as a control (0.1 ml/100 gm body weight) or substance P (Sigma®) (40 μg/kg in saline, 0.1 ml/100 gm body weight) subcutaneously as well as hexamethonium (Sigma) (50 mg/kg) intraperitoneally in saline (0.1 ml/100 gm body weight), lidocaine (2%, 0.3 ml) intravesically, atropine (Sigma) (3 mg/kg in saline, 0.1 ml/100 gm body weight) intravenously, propranolol (Sigma) (3 mg/kg in saline, 0.1 ml/100 gm body weight) intravenously or phentolamine (Sigma) (10 mg/kg in saline, 0.1 ml/100 gm body weight) intravenously. After 1 hour the intravesical fluid was removed and the bladder was excised. Macrophage migration inhibitory factor levels in intraluminal fluid were measured by enzyme-linked immunosorbent assay and Western blotting.MIFexpression in bladder homogenates was examined using reverse transcriptase-polymerase chain reaction.ResultsIntravesical lidocaine or ganglionic blockage with hexamethonium prevented substance P induced macrophage migration inhibitory factor release. In addition, pretreatment with atropine and phentolamine but not propranolol also prevented macrophage migration inhibitory factor release. WhileMIFup-regulation in the bladder was increased with substance P treatment, it was only prevented by intravesical lidocaine.ConclusionsSubstance P induced macrophage migration inhibitory factor release in the bladder is mediated through nerve activation. Postganglionic parasympathetic (via muscarinic receptors) and sympathetic (via α-adrenergic receptors) fibers mediate macrophage migration inhibitory factor release, while activating bladder afferent nerve terminals up-regulatesMIF.