Tyagi Pradeep, Kadekawa Katsumi, Kashyap Mahendra, Pore Subrata, Yoshimura Naoki
Department of Urology, University of Pittsburgh, Pittsburgh, PA.
Department of Urology, University of Pittsburgh, Pittsburgh, PA.
Urology. 2016 Feb;88:57-65. doi: 10.1016/j.urology.2015.10.017. Epub 2015 Oct 30.
To investigate the time-dependent changes in expression of cytokines that characterizes the spontaneous recovery of reflex voiding after spinal cord injury (SCI). SCI is known to reorganize the neural circuitry of micturition reflex after injury.
Under isoflurane anesthesia, spinal cord of 18 adult female Sprague-Dawley rats was completely transected at the Th9-10 level. Awake cystometry was performed at each time point on controls and 6 SCI animals, and bladder was then harvested for analysis of 29 proteins Millipore kit or enzyme-linked immunosorbent assay. Prophylactic dose of ampicillin 100 mg/kg was administered periodically to all SCI animals.
Spontaneous recovery of voiding after SCI at 12 weeks was evident from increased intercontractile interval and voiding efficiency during cystometry. Expression of proinflammatory interleukins ([IL] IL-1α and IL-1β, IL-2, IL-5, IL-6, IL-18, tumor necrosis factor alpha [TNF-α]) and CXC chemokines (CXCL1, CXCL2, CXCL10), CX3CL1, and CCL2 showed significant elevation at 4 and at 8 weeks with slight decrease at 12 weeks. In contrast, expression of anti-inflammatory IL-10 and neuroprotective factors, CXCL-5, and leptin, was elevated at 8 and at 12 weeks (P < .05). In contrast, expression of CCL3, CCL5, and growth factors (vascular endothelial growth factor, nerve growth factor, epidermal growth factor, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor) did not show any significant temporal change after SCI.
Spontaneous recovery of reflex voiding at 12 weeks was marked by increased endogenous expression of anti-inflammatory cytokine IL-10 and neuroprotective factors, CXCL-5, and leptin, which suggests that pharmacological suppression of inflammation, can hasten the emergence of reflex voiding after SCI.
研究细胞因子表达的时间依赖性变化，这些变化表征了脊髓损伤（SCI）后反射性排尿的自发恢复情况。已知SCI会在损伤后重组排尿反射的神经回路。
在异氟烷麻醉下，将18只成年雌性Sprague-Dawley大鼠的脊髓在Th9-10水平完全横断。在每个时间点对对照组和6只SCI动物进行清醒膀胱测压，然后摘取膀胱，用Millipore试剂盒或酶联免疫吸附测定法分析29种蛋白质。定期给所有SCI动物施用100mg/kg的预防性剂量氨苄青霉素。
SCI后12周排尿的自发恢复表现为膀胱测压期间收缩间期和排尿效率增加。促炎白细胞介素（[IL]IL-1α和IL-1β、IL-2、IL-5、IL-6、IL-18、肿瘤坏死因子α[TNF-α]）和CXC趋化因子（CXCL1、CXCL2、CXCL10）、CX3CL1和CCL2的表达在4周和8周时显著升高，在12周时略有下降。相比之下，抗炎性IL-10和神经保护因子CXCL-5以及瘦素的表达在8周和12周时升高（P<.05）。相比之下，CCL3、CCL5和生长因子（血管内皮生长因子、神经生长因子、表皮生长因子、粒细胞集落刺激因子和粒细胞巨噬细胞集落刺激因子）的表达在SCI后未显示出任何显著的时间变化。
SCI后12周反射性排尿的自发恢复以抗炎细胞因子IL-10和神经保护因子CXCL-5以及瘦素的内源性表达增加为特征，这表明药理学上抑制炎症可加速SCI后反射性排尿的出现。
