Bladder function in a cannabinoid receptor type 1 knockout mouse
Bladder function in a cannabinoid receptor type 1 knockout mouse
复制标题
DOI：
10.1111/bju.12350
复制
发表时间：
2014-01-01
影响因子：
4.5
通讯作者：
Andersson, Karl-Erik
中科院分区：
文献类型：
--
作者：
Fuellhase, Claudius;Campeau, Lysanne;Andersson, Karl-Erik
目的通过器官浴（体外）和尿动力学（体内）实验评估大麻素1型（CB1）受体敲除（KO）小鼠模型的膀胱功能。材料与方法选用8周龄雌性野生型（WT）小鼠（C57BL/6） 20只和年龄匹配的CB1 KO小鼠20只。每组取6只小鼠进行脏器浴实验，分别观察氯巴酚暴露后膀胱组织条的收缩反应（氯巴酚浓度反应曲线[CCRC]；肌原性收缩）和电场刺激（EFS；神经原性收缩）。在不麻醉的情况下，每组14只小鼠进行膀胱测量实验，在膀胱导尿3天后评估标准尿动力学变量。结果CB1 KO小鼠膀胱条CCRCs与WT小鼠相似。然而，在电刺激过程中，CB1 KO小鼠膀胱条的收缩反应明显低于WT制剂，这表明CB1 KO小鼠膀胱收缩的神经元成分不同。在膀胱测量实验中，CB1 KO小鼠的排尿频率更高（平均[sem]排尿间隔较短，分别为3.24[0.29]和7.32 [0.5]min），膀胱容量较低（0.09[0.01]和0.18 [0.01]mL），排尿量较低（0.07[0.01]和0.14 [0.01]mL），膀胱依从性较低（0.007[0.001]和0.02 [0.002]mL/cmH（2)O），膀胱自发活动较高（5.1[0.5]和2.6 [0.6]cmH(2)O），均P < 0.05，学生t检验）。在WT小鼠中，全身给予利莫那班（SR141716），一种CB1受体拮抗剂，导致与CB1 KO小鼠相似的尿动力学变化。结论体外CB1 KO小鼠膀胱条对毒蕈碱受体刺激的反应与WT对照组相似，但对神经电刺激的反应较弱。在体内，CB1 KO小鼠比WT小鼠有更高的排尿频率和更多的自发活动。目前的研究结果表明，CB1受体参与外周神经和中枢神经对排尿的控制。
ObjectiveTo evaluate bladder function in an established cannabinoid type 1 (CB1) receptor knockout (KO) mouse model via organ-bath (in vitro) and urodynamic (cystometric; in vivo) experiments.Materials and MethodsIn all, 20 8-week-old female wildtype (WT) mice (C57BL/6) and 20 age-matched CB1 KO mice were used. Six mice from each group were used for the organ-bath experiments, where the contractile responses of bladder tissue strips after carbachol exposure (carbachol concentration response curve [CCRC]; myogenic contraction) and during electrical field stimulation (EFS; neurogenic contraction) were assessed. In all, 14 mice per group were used for cystometric experiments without any anaesthesia, in which standard urodynamic variables were assessed 3 days after bladder catheterisation.ResultsThe CCRCs of bladder strips from CB1 KO mice were similar to those of WT mice. However, during EFS the bladder strips from the CB1 KO mice had significantly lower contractile responses than WT preparations, indicating that in CB1 KO mice the neuronal component of bladder contraction was different. In cystometric experiments the CB1 KO mice had a higher micturition frequency (shorter mean [sem] inter-micturition interval of 3.24 [0.29] vs 7.32 [0.5] min), a lower bladder capacity (0.09 [0.01] vs 0.18 [0.01] mL) and micturition volume (0.07 [0.01] vs 0.14 [0.01] mL), a lower bladder compliance (0.007 [0.001] vs 0.02 [0.002] mL/cmH(2)O), and higher spontaneous bladder activity (5.1 [0.5] vs 2.6 [0.6] cmH(2)O) than WT mice (all P < 0.05, Student's t-test). In WT mice, systemic administration of rimonabant (SR141716), a CB1 receptor antagonist, resulted in urodynamic changes similar to those seen in the CB1 KO mice.ConclusionsIn vitro, bladder strips from CB1 KO mice responded to muscarinic receptor stimulation similarly as the WT controls, but were less responsive to electrical stimulation of nerves. In vivo, CB1 KO mice had a higher micturition frequency and more spontaneous activity than WT mice. The present findings suggest that CB1 receptors are involved in peripheral and central nervous control of micturition.