Central muscarinic mechanisms of bladder overactivity associated with Alzheimer type senile dementia.

目的：探讨清醒阿尔茨海默型老年性痴呆大鼠神经源性膀胱过度活动的机制。方法：将雄性Wistar大鼠置于立体定向仪中，采用鹅膏油酸(IA)(每只大鼠7.5μg/只)损毁双侧基底前脑(BF组)。对照组(假手术组，SO组)注射磷酸盐缓冲盐水(PBS)。注射IA/PBS后7~10d行膀胱测压(CMG)。记录CMG后，检测额叶皮质胆碱-乙酰转移酶(CAT)活性，以评估基底前脑向额叶皮质胆碱能神经元投射的损害。在清醒的BF大鼠上，观察侧脑室注射M受体激动剂奥曲莫林M或M_1受体拮抗剂哌仑西平的影响。在BF大鼠上也观察了哌仑西平的拮抗作用。奥曲莫林M或…的疗效观察在乌拉坦麻醉下，更多的吡伦西平被直接注入桥脑排尿中心。结果：膀胱容量明显小于注射IA前。注射IA后7~10天，膀胱容量约为SO大鼠的43%。BF大鼠额叶皮质CAT活性降低。奥曲莫林M增加BF大鼠的膀胱容量，而减少SO大鼠的膀胱容量。吡伦西平显著增加BF和SO大鼠的膀胱容量，并拮抗奥托莫林M的作用。在BF和SO大鼠的PMC内直接注射奥托莫林M可降低BF和SO大鼠的膀胱容量，而注射吡伦西平对CMG无影响。结论：大脑皮层M1 M系统对排尿反射通路有抑制作用。这种抑制机制的下调在阿尔茨海默型痴呆的膀胱过度活动中起着重要作用。脑干M2系统可能对排尿反射通路产生兴奋性影响。较少

OBJECTS : To investigate the mechanisms of neurogenic bladder overactivity in Alzheimer type senile dementia in a conscious rat model.METHODS : Male Wistar rats were placed in a stereotaxic apparatus, and subjected to bilateral lesion of the basal forebrain by means of ibotenic acid (IA) injection (7.5 μg/rat on each side)(BF rats). Phosphate buffered saline (PBS) was injected to control rats (sham operated rats ; SO rats). Cystometrograms (CMG) were obtained 7 to 10 days after IA/PBS injection. After CMG recording, choline-acetyltransferase (CAT) activities in the frontal cortices were assayed to assess the damage to cholinergic neuronal projections from basal forebrain to frontal cortices. The influences of intracerebroventricular administration of Oxotremorine M, muscarinic receptor agonist, or pirenzepine, M1 muscarinic receptor antagonist were investigated in conscious BF or SO rats. Antagonized effects of pirenzepine were also examined in BF rats. The effects of oxotremorine M or … More pirensepine directly injected into the PMC (pontine micturition center) were examined under urethane anesthesia.RESULTS : Bladder capacity become significantly smaller than before IA injection. Seven to 10 days after IA injection, bladder capacity was approximately 43% of SO rats. CAT activity in the frontal cortices was reduced in BF rats. Oxotremorine M increased bladder capacity in BF rats, while decreased in SO rats. Pirensepine significantly increased bladder capacity both in BF and SO rats, and antagonised the effect of oxotremorine M. Direct injection of oxotremorine M into the PMC decreased bladder capacity in BF and SO rats, while injection of pirensepine had no effects on CMG.CONCLUSIONS : These results indicate that M1 muscarinic system in the cerebral cortex has inhibitory influence to micturition reflex pathway. Down-regulation of this inhibitory mechanism plays an important role on overactive bladder in Alzheimer type dementia. M2 muscarinic system in the brainstem is likely to have excitatory influence on micturition reflex pathway. Less