α-硫辛酸对慢性脑低灌注大鼠脑单胺类神经递质和单胺氧化酶的影响

摘要

目的：观察α-硫辛酸(ALA)对慢性脑低灌注(CCH)血管性痴呆大鼠单胺类神经递质和单胺氧化酶的影响。方法健康成年雄性Wistar大鼠60只随机分为假手术组(SHAM组)、慢性脑低灌注组(CCH组)、低剂量治疗组(L-ALA组，50 mg/kg)和高剂量治疗组(H-ALA组，100 mg/kg)，每组15只。利用双侧颈动脉结扎术制备慢性脑低灌注模型，SHAM组手术步骤与CCH组相同但不结扎颈总动脉。从实验第29天起Morris水迷宫检测动物认知功能，水迷宫结束后取材，采用高效液相色谱仪检测去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)在大鼠前脑皮层的水平，分光光度计检测前脑皮层单胺氧化酶(MAO)的水平。结果与SHAM组比较，CCH组大鼠前脑皮层NE、DA和5-HT的含量均显著下降，MAO含量明显升高，差异均有统计学意义(P<0.05)；与CCH组比较，低剂量ALA和高剂量ALA治疗均能显著提高CCH大鼠前脑皮层组织的NE、DA和5-HT含量，降低MAO水平，差异均有统计学意义(P<0.05)。结论α-硫辛酸能够明显改善CCH大鼠的行为学异常，调节CCH大鼠脑内单胺类神经递质系统。%Objective To explore the effects of alpha-lipoic acid (ALA) on monoamine neurotransmitters and monoamine oxidase in rats with chronic cerebral hypoperfusion (CCH). Methods Sixty healthy adult male Wistar rats were randomly assigned into four groups: SHAM group, CCH group, low-dose ALA therapy group (50 mg/kg) and high-dose ALA therapy group (100 mg/kg). Bilateral common carotid arteries occlusion was used in healthy adult male Wistar rats to establish CCH model. Rats in SHAM group were operated similarly to CCH group without occlusion of common carotid arteries. Morris water maze was used to evaluate spacial learning and memory function. HPLC was used to detect the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in the forebrain cor-tex, and monoamine oxidase (MAO) was measured spectrophotometrically. Results Compared with SHAM group, the contents of NE, E, DA and 5-HT significantly decreased and MAO significantly increased in the CCH group, and the differences were statistically significant (P<0.05). Both low-dose ALA and high-dose ALA could significantly increase NE, DA and 5-HT levels, and significantly decrease MAO level in the CCH rats (P<0.05). Conclusion ALA could sig-nificantly improve behavioral alterations and restore central monoamine neurotransmitters system in rats with chronic cerebral hypoperfusion.