Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Am J Physiol Renal Physiol. 2010 Mar;298(3):F589-600. doi: 10.1152/ajprenal.00628.2009. Epub 2009 Dec 23.
Chemokines, otherwise known as chemotactic cytokines, are proinflammatory mediators of the immune response and have been implicated in altered sensory processing, hyperalgesia, and central sensitization following tissue injury or inflammation. To address the role of CXCL12/CXCR4 signaling in normal micturition and inflammation-induced bladder hyperreflexia, bladder inflammation in adult female Wistar rats (175-250 g) was induced by injecting cyclophosphamide (CYP) intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every 3rd day for 10 days) time points. CXCL12, and its receptor, CXCR4, were examined in the whole urinary bladder of control and CYP-treated rats using enzyme-linked immunosorbent assays (ELISAs), quantitative PCR (qRT-PCR), and immunostaining techniques. ELISAs, qRT-PCR, and immunostaining experiments revealed a significant (P < or = 0.01) increase in CXCL12 and CXCR4 expression in the whole urinary bladder, and particularly in the urothelium, with CYP treatment. The functional role of CXCL12/CXCR4 signaling in micturition was evaluated using conscious cystometry with continuous instillation of saline and CXCR4 receptor antagonist (AMD-3100; 5 microM) administration in control and CYP (48 h)-treated rats. Receptor blockade of CXCR4 using AMD-3100 increased bladder capacity in control (no CYP) rats and reduced CYP-induced bladder hyperexcitability as demonstrated by significant (P < or = 0.01) increases in intercontraction interval, bladder capacity, and void volume. These results suggest a role for CXCL12/CXCR4 signaling in both normal micturition and with bladder hyperreflexia following bladder inflammation.
趋化因子，也称为趋化细胞因子，是免疫反应的促炎介质，已被牵连到组织损伤或炎症后感觉处理改变、痛觉过敏和中枢敏化。为了研究 CXCL12/CXCR4 信号在正常排尿和炎症诱导的膀胱反射亢进中的作用，通过腹腔内注射环磷酰胺 (CYP) 在成年雌性 Wistar 大鼠 (175-250 g) 中诱导膀胱炎症，急性 (150 mg/kg；4 h)、中间 (150 mg/kg；48 h) 和慢性 (75 mg/kg；每隔 3 天，共 10 天) 时间点。使用酶联免疫吸附测定 (ELISA)、定量 PCR (qRT-PCR) 和免疫染色技术检查对照和 CYP 处理大鼠整个膀胱中的 CXCL12 和其受体 CXCR4。ELISA、qRT-PCR 和免疫染色实验显示，CYP 处理后整个膀胱，特别是尿路上皮中，CXCL12 和 CXCR4 表达显著增加 (P < or = 0.01)。使用连续生理盐水灌注和 CXCR4 受体拮抗剂 (AMD-3100；5 microM) 给药的清醒膀胱测压法评估 CXCL12/CXCR4 信号在排尿中的功能作用，在对照和 CYP (48 h) 处理的大鼠中进行。使用 AMD-3100 阻断 CXCR4 受体增加了对照 (无 CYP) 大鼠的膀胱容量，并降低了 CYP 诱导的膀胱过度兴奋性，表现为明显的 (P < or = 0.01) 收缩间隔、膀胱容量和排空量增加。这些结果表明，CXCL12/CXCR4 信号在正常排尿和膀胱炎症后的膀胱反射亢进中均有作用。
