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

目的：探讨阿尔茨海默型老年痴呆大鼠神经源性膀胱过度活动的机制。方法：将雄性Wistar大鼠置于立体定向装置中，双侧基底前脑损伤处注射伊博tenic acid (IA)（每侧7.5 μg/大鼠）（BF大鼠）。对照大鼠（假手术大鼠；SO大鼠）注射磷酸缓冲盐水（PBS）。注射IA/PBS后7 ~ 10天获得膀胱造影（CMG）。CMG记录后，测定脑额皮质胆碱乙酰转移酶（CAT）活性，评估基底前脑向额皮质胆碱能神经元投射的损伤。对有意识BF或SO大鼠脑室内给予氧tremorine M、毒蕈碱受体激动剂或匹伦西平、M1毒蕈碱受体拮抗剂的影响进行了研究。在BF大鼠中也检测了吡仑西平的拮抗作用。在氨基甲酸乙酯麻醉下，观察直接向脑桥排尿中心（PMC）注射多剂量丙烯血平对脑桥排尿中心的影响。结果：膀胱容量明显小于注射前。注射IA后7 ~ 10天，膀胱容量约为SO大鼠的43%。BF大鼠额皮质CAT活性降低。氧tremorine M增加BF大鼠膀胱容量，而降低SO大鼠膀胱容量。在BF大鼠和SO大鼠中，直接在PMC中注射氧tremorine M可降低膀胱容量，而在CMG大鼠中注射丙烯氨苄对CMG无影响。结论：提示大脑皮层M1毒蕈碱系统对排尿反射通路具有抑制作用。这种抑制机制的下调在阿尔茨海默型痴呆患者膀胱过度活动中起重要作用。脑干M2毒蕈碱系统可能对排尿反射通路有兴奋性影响。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