ZDY102对拟痴呆大鼠脑M受体的影响

The effect of ZDY102 on brain M receptor in dementia model rats

目的 观察知母活性成分ZMS的异构体ZDY10 2对拟痴呆大鼠脑M受体及学习记忆功能的影响。方法 大鼠单侧脑基底核部位定位注射 β 淀粉样肽 (2 5～ 35 )和鹅蕈膏酸造成拟痴呆模型 ,设立不同剂量ZDY10 2治疗组、模型组和对照组 (注射生理盐水 ) ,分别用Y 迷宫测定学习记忆能力及放射配基结合分析法测定注射同侧脑内M胆碱受体密度。结果 拟痴呆模型大鼠学习和记忆成绩和脑M受体密度明显低于对照组。连续两个月喂服ZDY10 2的模型大鼠学习和记忆能力显著好于对照组 ,脑M受体密度也显著提高 ,而且脑M受体密度与动物的学习记忆能力呈显著正相关。结论 ZDY10 2能明显改善拟痴呆大鼠的学习记忆能力 ,同时能显著提高脑内M受体密度 ,从两者的显著正相关来看 ,提高脑M受体密度可能是ZDY10 2改善拟痴呆模型学习记忆的重要机制。和以往对知母活性成分的研究结果相比较可以看出 ,2

Aim To observe the effect of ZDY102, a C25 stereo-isomer of ZMS, the active component of Zhimu, on brain M receptor density of dementia model animals and the correlation with its effect on learning/memory ability. Methods The rats were randomly divided into five groups: control group, model group, model given orally for 2 months with 3.6 mg·kg -1·d -1 of ZDY102 treatment, model treated with 9.0 mg·kg -1·d -1 of ZDY102, and model treated with 18.0 mg·kg -1·d -1 of ZDY102. Dementia model was produced by single unilateral injection of 4 μl of normal saline containing 4 μg of β-amyloid (25～35) and 1 μg of ibotenic acid into right basal ganglion region with the aid of a stereotaxic equipment. The brain muscarinic receptor density was analyzed with single-site binding assay using 3H-quinuclidinyl benzilae(QNB). The learning/memory ability was measured by Y-maze performance. Results Two months after model production, the learning and memory ability as well as the density of muscarinic receptor in brain were significantly decreased in model rats compared with those in control rats. Parallel models treated with daily oral administration of ZDY102 for two months improved in learning and memory ability and their muscarinic receptor density was significantly increased when compared with model rats. The correlation coefficient between total M receptor densities and the learning/memory ability was significant when examined with linear regression. Conclusion ZDY102 can significantly improve the learning and memory ability and increase the brain muscarinic receptor density of the model. Since brain muscarinic receptors are closely correlated to learning and memory, up-regulation of M receptor density might play a very important role in the therapeutic effect of ZDY102.