参麻益智胶囊对血管性痴呆大鼠体内过氧化状态的影响

背景血管性痴呆的发生和发展与氧自由基代谢的异常关系密切,在痴呆病的药效学实验中常以氧自由基的代谢作为主要指标.目的建立多发性脑梗死动物模型,测定大鼠血液与脑组织内的脂质过氧化物含量、超氧化物歧化酶及谷胱甘肽过氧化物酶的活性,从而分析参麻益智胶囊对血管性痴呆大鼠体内过氧化状态的影响.设计随机对照单一样本实验.单位辽宁省基础医学研究所药理研究室.材料实验于1997-07/1998-11在辽宁省基础医学研究所药理研究室完成.选取健康Wistar大鼠96只,随机分为6组,即正常对照组、模型对照组、阳性药对照组、参麻益智胶囊高剂量组、参麻益智胶囊中剂量组、参麻益智胶囊低剂量组,16只/组.参麻益智胶囊由人参、天麻等中药总提取物组成,每克药粉含生药2.7 g,由中国中医研究院西苑医院提供.方法除正常对照组外,其余各组均建立多发性脑梗死动物模型.正常对照组及模型对照组均灌胃给予生理盐水0.5 mL;参麻益智胶囊高、中、低剂量组分别灌胃给药3.2,1.6,0.8g/kg;阳性药对照组灌胃给予双氢麦角碱1 mg/Kg.各组于栓塞后1周开始给药,1次/d,连续6周.脂质过氧化物含量按荧光法测定,超氧化物歧化酶活性应用邻苯三酚自氧化法测定,谷胱甘肽过氧化物酶活性按Hafenam方法测定.主要观察指标各组大鼠血浆与脑组织中脂质过氧化物含量、谷胱甘肽过氧化物酶和超氧化物歧化酶活性的测定.结果实验纳入96只大鼠全部进入结果分析.①各组大鼠血浆中各项生化指标测定结果脂质过氧化物含量模型对照组及阳性药对照组明显高于正常对照组(16.0±1.6),(16.0±1.7),(13.4±1.0)μmol/L,t=4.20～10.58,P均＜0.01],参麻益智高、中、低剂量组显著高于模型对照组(13.1±1.5),(13.3±0.8),(13.9±1.0),(16.0±1.6)μmol/L,t=4.39～11.69,P均＜0.01];与正常对照组谷胱甘肽过氧化物酶活性比较,模型对照组、参麻益智高、中、低剂量组均明显降低(5.0±1.6),(3.6±0.8),(3.6±1.1),(3.6±0.8),(3.7±0.9)μmol/(g·s),P＜0.05,P＜0.05,P＜0.05,P＜0.01];与正常对照组超氧化物歧化酶活性比较,阳性药对照组明显升高(31.7±6.7),(38.4±8.4)μmol/(g·s),t=2.57～3.64,P＜0.05].②各组大鼠脑组织中各项生化指标测定结果脂质过氧化物含量模型对照组、阳性药对照组及参麻益智低剂量组均明显低于正常对照组(140.0±20.0),(130.0±20.0),(102.0±12.0),(83.0±21.0)μmol/L,P＜0.01,P＜0.01,P＜0.05],参麻益智高、中、低剂量组显著高于模型对照组(95.0±13.0),(96.0±32.0),(102.0±12.0),(140.0±20.0)μmol/L,t=4.28～11.87,P均＜0.01];与正常对照组谷胱甘肽过氧化物酶活性比较,模型对照组及阳性药对照组均明显降低(0.5±0.1),(0.3±0.1),(0.4±0.1)μmol/(g·s),P＜0.01,P＜0.05],参麻益智中、低剂量组显著高于模型对照组(0.5±0.2),(0.5±0.1),(0.3±0.1)μmol/(g·s),t=4.28～11.87,P均＜0.01];与正常对照组超氧化物歧化酶活性比较,模型对照组及阳性药对照组明显降低(23.4±3.3),(16.7±3.3)(16.7±3.3)μmol/(g·s),t=4.45～10.69,P均＜0.01],与模型对照组比较,参麻益智高、中、低剂量组均显著升高(16.7±3.3),(23.4±3.3),(21.7±6.7),(21.7±3.3)μmol/(g·s),t=4.28～11.87,P均＜0.01].结论血管性痴呆大鼠超氧化物歧化酶及谷胱甘肽过氧化物酶抗过氧化活性降低,体内过氧化反应增强.参麻益智胶囊通过提高超氧化物歧化酶和谷胱甘肽过氧化物酶活性而改善过氧化状态,对血管性痴呆具有治疗作用.

Effects of Cenma Yizhi Capsule on peroxidative status in viva in rats with vascular dementia

BACKGROUND: The incidence and progress of vascular dementia (VD)is closely related to the abnormal metabolism of oxygen-derived free radicals, whose metabolism is often the main index in pharmacodynamic experiments on dementia.OBJECTIVE: To establish the animal model of multiple cerebral infarction and determine the content of lipid peroxide and the activity of superoxide dismutase and glutathione peroxidase in the blood and cerebral tissues so as to analyze the effects of Cenma Yizhi Capsule on the oxidative status in vivo in VD rats.DESIGN: Randomized controlled single sample trial.SETTING: Department of Pharmacology, Institute of Basic Medicine of Liaoning Province.MATERIALS: This experiment was conducted in the Department of Pharmacology, Institute of Basic Medicine of Liaoning Province, between July 1997 and November 1998. Totally 96 healthy Wistar rats were recruited and randomized into 6 groups: normal control group, model control group ,positive drug control group, Cenma Yizhi Capsule high-dose group, Cenna Yizhi Capsule medium-dose group, and Cenma Yizhi Capsule low-dose group with 16 rats in each group. Cenma Yizhi Capsules, the compound of the total extract of ginseng, Tianma and other Chinese herbal medicine (each gram contained 2.7 g drug), were provided by Xiyuan Hospital of the Chinese Academy of Traditional Chinese Medicine.METHODS: The animal model of multiple cerebral infarction was established in all the groups except normal control group. Normal saline of 0.5 mL was gastrically perfused into the rats in Cenma Yizhi Capsule high-, medium- and low-dose groups; dihydroergotamine mesylate of 1mg/kg was gastrically perfused into the rats in positive drug control group. Rats in each group were given the drug 1 week after embolism, once a day for 6 consecutive weeks. The content of lipid peroxide was determined with fluorescence method, and the activity of superoxide dismutaseand glutathione peroxidase was determined with self-oxidation method of pyrognllol and Hafenam method, respectively.MAIN OUTCOME MEASURES: The content of lipid peroxide, and the activity of glutathione peroxidase and superoxide dismutase in the blood and cerebral tissues of the rats in each group.results of biochemical indexes in the blood of the rats: The content of lipid peroxide was significantly higher in model control group and positive drug control group than in normal control group (16.0±1.6), (16.0±1.7),(13.4±1.0)μmol/L, t=4.20-10.58, all P ＜ 0.01]; it was significantly higher in Cenma Yizhi Capsule high-, medium- and low-dose groups than in model control group (13.1±1.5), (13.3±0.8), (13.9±1.0), (16.0±1.6)μmol/L,t=4.39-11.69, all P ＜ 0.01]. The activity of glutathione peroxidase in model control group, and Cenma Yizhi Capsule high-, medium- and low-dose groups was significantly low compared with that in normal control group P ＜ 0.05, P ＜ 0.05, P ＜ 0.01]. The activity of superoxide dismutase in positive control group was significantly higher than that in normal control termination results of biochemical indexes in the cerebral tissues of the rats in each group: The content of lipid peroxide in model control group,positive drug control group and Cenma Yizhi Capsule low-dose group was significantly lower than that in normal control group (140.0 ±20.0),(130.0±20.0), (102.0±12.0), (83.0±21.0)μmol/L, P ＜ 0.01, P ＜ 0.01, P ＜ 0.05];it was significantly higher in Cenma Yizhi high-, medium- and low-dose groups than in model control group (95.0±13.0), (96.0±32.0), (102.0±12.0),(140.0±20.0)μmol/L, t=4.28-11.87, all P ＜ 0.01]. The activity of glutathione peroxidase in model control group and positive drug control group was significantly lower than that in normal control group (0.5±0.1),higher in Cenma Yizhi medium- and low-dose groups than in model con P ＜ 0.01]. The activity of superoxide dismutase in model control group and positive drug control group was significantly lower than that in normal conP ＜ 0.01]. It was significantly increased in Cenma Yizhi high-, medium- and low- dose groups compared with that in model control group (16.7±3.3),CONCLUSION: Anti-oxidative activities of superoxide dismutase and glutathione peroxidase in rats with vascular dementia were decreased, and the oxidative reaction in vivo was enhanced. Cenma Yizhi Capsule can improve the oxidative status through enhancing the activities of superoxide dismutase and glutathione peroxidase, and has therapeutic effects on vascular dementia.