Pan Hui Q, Kerns James M, Lin Dan L, Sypert David, Steward James, Hoover Christopher R V, Zaszczurynski Paul, Butler Robert S, Damaser Margot S
Cleveland Clinic, 9500 Euclid Ave., ND20, Cleveland, OH 44195, USA.
Am J Physiol Renal Physiol. 2009 Feb;296(2):F277-83. doi: 10.1152/ajprenal.90602.2008. Epub 2008 Dec 17.
A dual childbirth injury model, including vaginal distension (VD) and pudendal nerve crush (PNC), may best represent the injuries seen clinically. The objective of this study was to investigate urethral function, anatomy, and neurotrophin expression after several simulated childbirth injuries. Groups of 140 rats underwent PNC, VD, PNC+VD, or neither (C). Four days after injury, all injury groups had significantly decreased leak-point pressure (LPP) compared with C rats. Ten days after injury, LPP in PNC and PNC+VD rats remained significantly lower than C rats. Three weeks after injury, LPP in all injury groups had recovered to C values. Histological evidence of injury was still evident in the external urethral sphincter (EUS) after VD and PNC+VD 10 days after injury. Three weeks after injury, the EUS of PNC+VD rats remained disrupted. One day after VD, brain-derived neurotrophic factor (BDNF) expression in the EUS was reduced, while neurotrophin-4 (NT-4) and nerve growth factor (NGF) expression was unchanged. BDNF, NT-4, and NGF expression was dramatically upregulated in the EUS after PNC. After PNC+VD, NGF expression was upregulated, and BDNF and NT-4 expression was upregulated somewhat but not to the same extent as after PNC. Ten days after injury, PNC+VD had the least number of normal nerve fascicles near the EUS, followed by PNC and VD. Twenty-one days after injury, all injury groups had fewer normal nerve fascicles, but without significant differences compared with C rats. PNC+VD therefore provides a more severe injury than PNC or VD alone.
一种双分娩损伤模型,包括阴道扩张(VD)和阴部神经挤压(PNC),可能最能代表临床上所见的损伤。本研究的目的是调查几种模拟分娩损伤后尿道功能、解剖结构和神经营养因子表达情况。将140只大鼠分为几组,分别接受PNC、VD、PNC + VD或不接受任何处理(C组)。损伤后4天,与C组大鼠相比,所有损伤组的漏点压力(LPP)均显著降低。损伤后10天,PNC组和PNC + VD组的LPP仍显著低于C组大鼠。损伤后3周,所有损伤组的LPP均恢复到C组水平。损伤后10天,VD组和PNC + VD组的尿道外括约肌(EUS)仍有明显的损伤组织学证据。损伤后3周,PNC + VD组大鼠的EUS仍有破坏。VD后1天,EUS中脑源性神经营养因子(BDNF)表达降低,而神经营养因子-4(NT-4)和神经生长因子(NGF)表达未改变。PNC后,EUS中BDNF、NT-4和NGF表达显著上调。PNC + VD后,NGF表达上调,BDNF和NT-4表达也有所上调,但程度不如PNC后。损伤后10天,PNC + VD组在EUS附近的正常神经束数量最少,其次是PNC组和VD组。损伤后21天,所有损伤组的正常神经束数量均减少,但与C组大鼠相比无显著差异。因此,PNC + VD造成的损伤比单独的PNC或VD更严重。