二苯乙烯苷对鹅膏蕈氨酸致痴呆大鼠模型脑内胆碱能系统的影响

 目的研究何首乌有效成分二苯乙烯苷(2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷,简称TSG)对胆碱能损伤致痴呆大鼠的保护作用。方法采用鹅膏覃氨酸(IBO)基底前脑注射造成模型大鼠脑内胆碱能系统损伤,模拟老年性痴呆动物模型。实验分为假手术、模型、阳性对照药盐酸多奈哌齐(多奈哌齐1.2mg·kg^-1)、TSG小剂量(30mg·kg^-1)、中剂量(60mg·kg^-1)和大剂量(120mg·kg^-1)组,灌胃给药1个月后,取脑分区测定皮层和海马胆碱乙酰基转移酶、乙酰胆碱酯酶活性,M-胆碱能受体结合力。胆碱乙酰基转移酶活性测定用放射化学法,乙酰胆碱酯酶活性测定用羟胺比色法,M-胆碱能受体结合力测定用放射配基结合实验。结果IBO模型大鼠皮层和海马胆碱乙酰基转移酶活性降低,M-胆碱能受体结合力明显下降;皮层乙酰胆碱酯酶活性下降。TSG小剂量可提高模型大鼠皮层和海马胆碱乙酰基转移酶活性;对于M-胆碱能受体结合力的下降,TSG各剂量组均有明显的改善作用;对于皮层乙酰胆碱酯酶活性的下降,TSG中、大剂量组有一定提升作用。结论TSG可明显改善模型动物胆碱能系统的损伤,对于老年性痴呆的治疗有重要意义。

Effects of tetrahydroxystilbene glucoside on cholinergic system in dementia rats model induced by ibotenic acid

OBJECTIVE To investigate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-fl-glucoside (TSG), one of effective components in Polygonum multiflorum, on brain cholinergic function in rats suffered from Alzheimer's disease.METHODS Basal forebrain of rats were injured by 10 μg ibotenic acid (IBO) injection in each side. Rals were divided into six groups and treated with sham operation, blank control, positive control drug donepezil hydrochloride, TSG low dose (30 mg·kg^-1), medium dose (60 mg·kg^-1) and high dose (120 mg·kg^-1) respectively. The drugs were intragastrically administrated for 1 month after successful development of models. Choline-acetyl-transfer-tase(ChAT) in cortex and hippocampus was measured by radiochemical method. Acetylcholinesterase activity was measured by hydroxylamine colorimetry. M-cholinergic receptor binding was assayed by radio binding.RESULTS Choline-acetyl-transfertase activity and M-cholinergic receptor binding were inhibited in the hippocampus and cortex of model rats. TSG increased the ChAT activity at low dose and significantly improved M-cholinergic receptor binding at 3 doses in both cortex and hippocampus. The activity of acetylcholinesterase( AChE) decreased in cortex but no effect was on hippocampus. TSG at middle and high dose increased AchE activity in cortex and didn' t affect the AchE in hippocampus. CONCLUSION TSG significantly improved the cholinergic damage in model rats, and it may play an important role in Alzheimer's disease therapy.