目的 評價丹皮酚與銀杏葉提取物1:1組合物對大鼠腦缺血再灌注損傷的保護(hù)作用。方法 尼莫地平(10.8 mg/kg)組、丹皮酚(37.5 mg/kg)組、銀杏葉提取物(37.5 mg/kg)組以及丹皮酚銀杏葉提取物1:1組合物(75.0 mg/kg)組大鼠灌胃給予相應(yīng)藥物,給藥容積10 mL/kg,ig給藥6 d后大腦中動脈栓塞造模,腦缺血再灌注后4、24 h進(jìn)行觀察,計算行為學(xué)評分;動物取腦,測定腦梗死面積,計算腦梗死率;大鼠腦缺血再灌注后24 h后,測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)水平和腦組織中基質(zhì)金屬蛋白酶-9(MMP-9)、GABA、Glu含量。結(jié)果 與模型組比較,腦缺血再灌注22 h后,各組大鼠行為學(xué)評分均有降低趨勢,其中組合物組的降低作用的差異具有顯著性(P< 0.05);與模型組比較,腦缺血再灌注24 h后,銀杏葉提取物、丹皮酚、組合物組大鼠腦梗死率均明顯降低,差異具有顯著性(P< 0.01);與模型組比較,組合物組大鼠血清中SOD水平、丹皮酚和組合物組血清中GABA水平顯著升高(P< 0.05),銀杏葉提取物、丹皮酚、組合物組大鼠血清中MDA水平、組合物組血清中Glu水平顯著降低(P< 0.01、0.05);丹皮酚和組合物組大鼠腦組織中MMP-9、Glu含量顯著降低(P< 0.01、0.05),組合物組腦組織中GABA含量顯著升高(P< 0.01)。結(jié)論 丹皮酚銀杏葉提取物組合物對大鼠腦缺血再灌注損傷具有保護(hù)作用,其作用機(jī)制可能是通過抗氧化損傷、平衡興奮性氨基酸與抑制性氨基酸濃度、調(diào)節(jié)MMP-9表達(dá)量有關(guān)。

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 of Ginkgo 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 of Ginkgo 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.

國家重大新藥創(chuàng)制科技重大專項(2013ZX09402203)