银杏蜜环口服溶液对多发性脑梗死大鼠模型的影响

Effects of Yinxing Mihuan Oral Solution for Rat Models with Multiple Cerebral Infarction

目的:银杏蜜环口服溶液是由银杏叶和蜜环菌组合而成的上市药物,临床用于缺血性心脑血管疾病,本研究探讨该药对大鼠多发性脑梗死(Multiple Cerebral Infacrtion,MCI)模型的影响。方法:将大鼠随机分为假手术组,模型组,金纳多组(18 mg/kg),银杏叶提取物组(9 mg/kg),天麻蜜环菌素片组(600 mg/kg),天麻蜜环菌粉组(300 mg/kg),银杏蜜环口服溶液组(618 mg/kg),银杏蜜环口服溶液组(309 mg/kg)。从大鼠颈总动脉向大脑中动脉方向注射荧光微球混悬血清,致使大脑动脉多发性阻塞,造成大鼠多发性脑梗死模型。灌胃给药28 d,末次给药后观察药物对大鼠神经功能评分、抓力、血清TNF-α、脑内氨基酸类神经递质及脑组织形态学的影响。结果:MCI模型大鼠神经功能有显著障碍,抓力显著降低,脑组织内谷氨酸(Glu)和γ-氨基丁酸(GABA)水平显著升高,血清TNF-α水平升高,与假手术组大鼠比较,差异有统计学意义(P<0.05)。组织学检查显示,脑组织受损,有明显的梗死灶,神经细胞排列紊乱,炎性细胞浸润等病理改变,免疫组化显示CD34、GFAP有自修复的表达,Neu N低表达。给药28 d后,银杏蜜环口服溶液神经功能明显改善,抓力增加,脑内Glu和GABA显著降低,血清TNF-α水平显著下降,与模型组比较,差异有统计学意义(P<0.05~0.01);病理结果显示,银杏蜜环口服溶液可保护脑缺血,改善由此导致的神经缺损程度;免疫组化结果显示,银杏蜜环口服溶液可明显促进血管内皮细胞、胶质细胞及神经元修复。银杏蜜环口服溶液对神经功能的改善和脑内Glu、GABA水平的降低作用显著优于银杏叶提取物;增加抓力作用显著优于天麻蜜环菌;降低血清TNF-α水平程度则同时优于两者。结论:银杏蜜环口服溶液有保护脑缺血,改善神经功能的作用,复方优于单一组份,且有一定的协同增效的作用。

Objective： To investigate the effects of Yinxing Mihuan Oral Solution combined with Ginkgo Leaf Extracts and Armillariella Mellea Powders（ GLE/AMP Oral Solution）,a marketed drug for ischemic cardio-cerebrovascular diseases in rat models of multiple cerebral infarction（ MCI）. Methods： SD rats were randomly divided into sham group,model group,ginaton group（ 18 mg/kg）,Extract of Ginkgo Biloba（ EGB） group（ 9 mg/kg）,armillaria mellea Tablets group（ 600 mg/kg）,armillaria mellea Powder group（ 300 mg/kg）,and Yinxing Mihuan Oral Solution groups（ 618 mg/kg and 309 mg/kg）. The multiple cerebral infarction rat models were established by injection of fluorescent microsphere suspension serous into the direction of middle cerebral artery through arteria carotis communis. After intragastric administration for 28 days,the effects of each group were tested,including neurological function score,grasping force,concentration of serum TNF-α,level of amino acid neurotransmitters and pathomorphology in brain tissue were investigated. Results： Compared with the sham group,significant neurological function impairment was observed in the MCI model,with reduced grasping force,as well as higher level of Glutamate（ Glu） and γ-aminobutyric acid（ GABA） in the brain and TNF-α in the serum. Pathological observation showed brain damage with significant infarcts,disorganized neurons arrangement and inflammatory cell infiltration. The immunohistochemistry analysis indicated self-repair expression of CD34 and GFAP,and low expression of Neu N. After administration of Yinxing Mihuan Oral Solution for 28 days,the neurological function was improved,and the grasping force was increased. The level of Glu and GABA in the brain and TNF-α in the serum were decreased compared with those in the model group（ P〈0. 05 - 0. 01）. Pathological observation showed that the Yinxing Mihuan Oral Solution could improve the degree of neurological function impairment,and the immunohistochemistry analysis indicated the Yinxing Mihuan Oral Solution could significantly promote the repair of cerebrovascular endothelial cell,glia and neuron. Besides,the effects of Yinxing Mihuan Oral Solution on improvement of neurological function and reducing the level of Glu and GABA in the brain were superior than that in the EGB group; the effect of Yinxing Mihuan Oral Solution in grasping force was superior than that in the Armillaria Mellea Powder group; and the effect of GLE/AMP Oral Solution in reducing the level of TNF-α in the serum was superior to that in the EGB group and Armillaria Mellea Powder group. Conclusion： The Yinxing Mihuan Oral Solution could protect cerebral ischemia and improve neurological function impairment,and combination use of Ginkgo Leaf Extracts and Armillariella Mellea Powders was superior in single component,represented certain synergistic interaction effect.