Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA.
Am J Physiol Regul Integr Comp Physiol. 2013 Jul 15;305(2):R147-56. doi: 10.1152/ajpregu.00089.2013. Epub 2013 May 8.
Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P ≤ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P ≤ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P ≤ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P ≤ 0.01) increased at all monofilament forces tested (0.1-4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P ≤ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity.
应激会加重人类下尿路功能性疾病的症状，包括间质性膀胱炎（IC）/膀胱疼痛综合征（BPS）和膀胱过度活动症（OAB），但其导致症状恶化的机制尚不清楚。这些研究使用雄性大鼠的应激动物模型，探讨了应激对排尿反射结构和功能的影响。大鼠接受了 7 天的重复变量应激（RVS）。RVS 后，采集并称重靶器官（膀胱、胸腺、肾上腺）组织。在 RVS 后，通过酶联免疫吸附试验（ELISA）测量膀胱中伊文思蓝（EB）浓度和组织胺、髓过氧化物酶（MPO）、神经生长因子（NGF）、脑源性神经营养因子（BDNF）和趋化因子 12（CXCL12）的蛋白含量。在 RVS 后，通过在清醒大鼠中连续、开放式膀胱内输注盐水来评估膀胱功能。RVS 第 5 天，体重增加明显（P ≤ 0.01）减少，肾上腺重量明显（P ≤ 0.05）增加。RVS 后，膀胱中组织胺、MPO、NGF 和 CXCL12 蛋白表达明显（P ≤ 0.01）增加。RVS 后，所有单丝力（0.1-4 g）测试的后足和骨盆区域的躯体敏感性明显（P ≤ 0.01）增加。RVS 后，收缩间期、输注量和排空量明显（P ≤ 0.01）减少。这些研究表明，RVS 后排尿频率、组织胺、MPO、NGF 和 CXCL12 膀胱含量和躯体敏感性增加，提示应激对膀胱功能和躯体敏感性的影响与炎症有关。
