丹皮酚银杏叶提取物组合物对大鼠脑缺血再灌注损伤的保护作用研究

Protection of combination of paeonol and Ginkgo biloba extracts on cerebral ischemia reperfusion injury in rats

目的评价丹皮酚与银杏叶提取物1∶1组合物对大鼠脑缺血再灌注损伤的保护作用。方法尼莫地平(10.8 mg/kg)组、丹皮酚(37.5 mg/kg)组、银杏叶提取物(37.5 mg/kg)组以及丹皮酚银杏叶提取物1∶1组合物(75.0 mg/kg)组大鼠灌胃给予相应药物,给药容积10 m L/kg,ig给药6 d后大脑中动脉栓塞造模,脑缺血再灌注后4、24 h进行观察,计算行为学评分;动物取脑,测定脑梗死面积,计算脑梗死率;大鼠脑缺血再灌注后24 h后,测定血清中自由基超氧化物歧化酶(SOD)、丙二醛(MDA)、γ-氨基丁酸(GABA)、谷氨酸(Glu)水平和脑组织中基质金属蛋白酶-9(MMP-9)、GABA、Glu含量。结果与模型组比较,脑缺血再灌注22 h后,各组大鼠行为学评分均有降低趋势,其中组合物组的降低作用的差异具有显著性(P<0.05);与模型组比较,脑缺血再灌注24 h后,银杏叶提取物、丹皮酚、组合物组大鼠脑梗死率均明显降低,差异具有显著性(P<0.01);与模型组比较,组合物组大鼠血清中SOD水平、丹皮酚和组合物组血清中GABA水平显著升高(P<0.05),银杏叶提取物、丹皮酚、组合物组大鼠血清中MDA水平、组合物组血清中Glu水平显著降低(P<0.01、0.05);丹皮酚和组合物组大鼠脑组织中MMP-9、Glu含量显著降低(P<0.01、0.05),组合物组脑组织中GABA含量显著升高(P<0.01)。结论丹皮酚银杏叶提取物组合物对大鼠脑缺血再灌注损伤具有保护作用,其作用机制可能是通过抗氧化损伤、平衡兴奋性氨基酸与抑制性氨基酸浓度、调节MMP-9表达量有关。

Objective To evaluate the protective effects of combination of paeonol and Ginkgo biloba extracts （1∶1） on cerebral ischemia reperfusion injury in rats.Methods Rats in nimodipine （10.8 mg/kg） group, Ginkgo biloba extracts （37.5 mg/kg） group, paeonol （37.5 mg/kg） group, and combination of paeonol and Ginkgo biloba extracts （1∶1） （75.0 mg/kg） group were ig administered with according drugs for 6 d, drug volumes were 10 mL/kg, and then were established middle cerebral artery occlusion models. Rats with cerebral ischemia reperfusion after 4 and 24 h were observed, and behavior scores were calculated. Animal brains were obtained, cerebral infarction areas were determined, and cerebral infarction rates were calculated. Cerebral ischemia reperfusion after 24 h, levels of free radicals, such as SOD, MDA, GABA, and Glu levels in serum, and contents of MMP-9, GABA, and Glu in brain tissues were determined.Results Compared with model group 22 h after cerebral ischemia reperfusion, behavior scores of rats in all experiment groups decreased, and there was significant difference on behavior score in combination group （P 〈 0.05）. Compared with model group 24 h after cerebral ischemia reperfusion, cerebral infarction rates ofGinkgo biloba extracts group, paeonol group, and combination group were obviously decreased, with significant differences between two groups （P 〈 0.01）. Compared with model group, SOD level in serum of combination group, and GABA levels in serum of paeonol group and combination group were significantly increased （P 〈 0.05）; MDA levels in serum ofGinkgo biloba extracts group, paeonol group, and combination group, and Glu level in serum of combination group were obviously decreased （P 〈 0.01, 0.05）; MMP-9 and Glu contents in brain tissues of paeonol group and combination group were significantly decreased （P 〈 0.01, 0.05）; GABA content in brain tissue of combination group was significantly increased （P 〈 0.01）.Conclusion Combination of paeonol and Ginkgo biloba extracts has a good effect in the cerebral ischemia reperfusion injury, which is related to anti-oxidant damage, concentration balance of excitatory amino acids and inhibitory amino acids, and regulation of MMP-9 expression.