Urinary Bladder Function and Somatic Sensitivity in Vasoactive Intestinal Polypeptide (VIP)-/- Mice

Urinary Bladder Function and Somatic Sensitivity in Vasoactive Intestinal Polypeptide (VIP)-/- Mice
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DOI:
10.1007/s12031-008-9100-8
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发表时间:
2008-11-01
影响因子:
3.1
通讯作者:
Vizzard, Margaret A.
Vizzard, Margaret A.
中科院分区:
医学4区
文献类型:
--
作者:
Studeny, Simon;Cheppudira, Bopaiah P.;Vizzard, Margaret A.

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血管活性肠多肽(VIP)是一种广泛分布于调节排尿的神经通路中的免疫调节神经肽。 VIP 也是一种内源性抗炎剂,已被建议用于开发炎症性疾病的疗法。在本研究中,我们检查了 VIP-/- 和同窝野生型 (WT) 对照的膀胱功能以及后爪和骨盆敏感性。我们证明 VIP-/小鼠的膀胱质量增加,滤纸上的尿斑更少但更大。在意识清醒、不受约束的小鼠中使用膀胱测压法,VIP-/-小鼠通过连续膀胱内输注盐水表现出增加的空隙体积和更短的收缩间隔。 VIP-/和 WT 小鼠之间的跨上皮阻力或水渗透性没有差异;然而,VIP-/-小鼠的尿素渗透性增加。通过急性给予环磷酰胺诱导膀胱炎症,在 VIP-/小鼠中表现出过度或延长的膀胱反射亢进以及后爪和骨盆敏感性。 VIP-/-小鼠膀胱反射亢进和躯体敏感性的变化可能反映了膀胱中神经营养因子和/或促炎细胞因子表达的增加。因此,这些变化可能进一步调节排尿的神经控制。
Vasoactive intestinal polypeptide ( VIP) is an immunomodulatory neuropeptide widely distributed in neural pathways that regulate micturition. VIP is also an endogenous anti- inflammatory agent that has been suggested for the development of therapies for inflammatory disorders. In the present study, we examined urinary bladder function and hindpaw and pelvic sensitivity in VIP-/- and littermate wildtype ( WT) controls. We demonstrated increased bladder mass and fewer but larger urine spots on filter paper in VIP-/mice. Using cystometry in conscious, unrestrained mice, VIP-/- mice exhibited increased void volumes and shorter intercontraction intervals with continuous intravesical infusion of saline. No differences in transepithelial resistance or water permeability were demonstrated between VIP-/and WT mice; however, an increase in urea permeability was demonstrated in VIP-/- mice. With the induction of bladder inflammation by acute administration of cyclophosphamide, an exaggerated or prolonged bladder hyperreflexia and hindpaw and pelvic sensitivity were demonstrated in VIP-/mice. The changes in bladder hyperreflexia and somatic sensitivity in VIP-/- mice may reflect increased expression of neurotrophins and/ or proinflammatory cytokines in the urinary bladder. Thus, these changes may further regulate the neural control of micturition.