葡萄籽原花青素对脑缺血再灌注损伤的保护作用

Protective effects of grape seed proanthocyanidins extract on cerebral ischemical reperfusion injury

目的:观察不同剂量葡萄籽原花青素对大鼠局灶性脑缺血再灌注损伤的神经保护作用及其作用的不同途径。方法:实验于2004-10/2005-07在安徽医科大学神经生物实验室完成。取SD大鼠160只随机分成假手术组、模型组和葡萄籽原花青素50,100,200mg/kg组5组,每组32只。①缺血前30min模型组大鼠腹腔注射1mL生理盐水,葡萄籽原花青素50,100,200mg/kg组腹腔注射相应浓度的葡萄籽原花青素液1mL,6h后重复给药一次;假手术组不给药。②采用线栓法制备脑缺血再灌注大鼠模型,假手术组不栓塞动脉。各组随机取8只大鼠在再灌注12h断头处死测脑组织含水量;其余大鼠在再灌注24h断头处死取脑,分别检测脑梗死体积比、缺血侧脑组织超氧化物歧化酶活性和丙二醛含量。结果:160只大鼠全部进入结果分析。①脑梗死体积比:葡萄籽原花青素100,200mg/kg组显著低于模型组(0.3077±0.0206,0.2972±0.0248,0.4594±0.0399,P<0.01)。②脑含水量:葡萄籽原花青素50,100,200mg/kg组均低于模型组[(79.97±0.76)%,(79.63±0.92)%,(79.67±0.51)%,(81.41±1.28)%,P<0.01]。③超氧化物歧化酶活性:葡萄籽原花青素50,100,200mg/kg组均高于模型组[(64.35±2.29),(64.52±2.20),(64.43±2.38),(39.72±6.94)NU/mg,P<0.01]。④丙二醛含量:葡萄籽原花青素50,100,200mg/kg组均低于模型组[(1.15±0.07),(1.11±0.16),(1.01±0.13),(1.42±0.23)μmol/g,P<0.01]。结论:①葡萄籽原花青素≥100mg/kg时可使局灶性脑缺血大鼠脑梗死体积减小,发挥有效的脑保护作用。②≥50mg/kg时即能增强抗氧化酶活性,减轻脂质过氧化损伤,减轻脑水肿程度。

AIM： To study the neuroprotective effect and the mechanism of different dose of grape seed proanthocyanidin extract （GSPE） on the focal cerebral ischemia-reperfusion injuries in rats. METHODS： The experiment was conducted in the neurobiologic laboratory of Anhui Medical Univesity between October 2004 and July 2005. The 160 SD rats were selected and divided by random into 5 groups： sham operation group, model group. and 50,100 and 200 mg/kg GSPE groups with 32 rats in each group. （1） The rats in the model group were treated with 1 mL saline before ischemia for 30 minutes. The rats in the 50,100 and 200 mg/kg GSPE groups were injected with GSPE 1 mL at the matched concentration, and 6 hours later they were given the same dosage of drug once. The rats in the sham operation group were not given drug. （2） Cerebral ischemia/ reperfusion rat models were made with thread lock method. The rats in the sham operation group did not embolize the artery. Eight rats were gained from every group randomly and reperfused for 12 hour, and then were killed by hreaking the heads. Content of water of brain tissue was detected. Other rats were killed by cutting the heads after reperfusion for 24 hours to gain the brain. Volume of cerebral infarction, activity of superoxide dismutase （SOD） of ischemic side of brain tissue and content of malondialdehyde （MDA） were detected, respectively. RESULTS： 160 rats were all involved in the result analysis. （1） Volume of cerehral infarction： It was lower significantly in the 100 and 200 mg/kg GSPE group than that in the model group （0.3077±0.020 6,0.297 2±0.024 8, 0.459 4±0.0399,P〈0.01 ）. （2） Content of water in brain： It was lower in the 50, 100 and 200 mg/kg GSPE group than that in the model group [ （ 79.97±0.76 ）%, （ 79.63±0.92 ）%, （ 79.67±0.51 ）%, （ 81.41±1.28 ）%, P〈0.01 ]. （3） Activity of SOD： It was higher in the 50, 100 and 200 mg/kg GSPE group than that in the model group [（64.35±2.29）, （64.52±2.20）, （64.43±2.38）, （39.72±6.94）NU/mg,P〈0.01]. （2） Content of MDA： It was lower in the 50, 100 and 200 mg/kg GSPE group than that in the model group [（1.15±0.07）, （ 1.11±0.16 ）, （1.01±0.13）, （ 1.42±0.23 ）μmol/g,P〈0.01]. CONCLUSION： （1） GSPE 〉1100 mg/kg can reduce the volume of cerebral infaretion in focal ischemic rats and has a effectively neuroprotective effect. （2） GSPE 〉150 mg/kg can increase the activity of anti-oxidase, the decrease lesion of lipid peroxidation and reduce the level of cerebral edema.