莪术二酮对脑缺血再灌注损伤小鼠认知功能及神经功能的保护作用研究

Protective effects of curdione on cognitive and neurological function in mice with cerebral ischemia-reperfusion injury

目的探讨莪术二酮对脑缺血再灌注损伤小鼠认知功能、神经功能及作用机制。方法使用线栓法建立小鼠脑缺血再灌注损伤模型,低分子肝素钠组、莪术二酮低、高剂量组和造模后分别灌胃给药1 mg/(kg·d),20 mg/(kg·d),60 mg/(kg·d),观察各组小鼠Morris水迷宫实验、行为学评分、脑梗死率、脑组织水含量,测定血清6-keto-PGF1α和6-keto-PGF1α/TXB2比值,脑组织匀浆c AMP和p-CREB的表达水平。结果与假手术组比较,模型组小鼠逃避潜伏期明显延长,站台穿越次数明显减少(P<0.01),行为学评分、脑梗死率、脑组织水含量、血清TXB2含量明显升高(P<0.01),血清6-keto-PGF1α、6-keto-PGF1α/TXB2比值、脑组织匀浆c AMP、p-CREB明显降低(P<0.01);与模型组比较,莪术二酮给药组逃避潜伏期明显缩短(P<0.05),站台穿越次数明显增加(P<0.05),行为学评分、脑梗死率和脑组织水含量明显降低(P<0.05),血清TXB2含量明显降低(P<0.01),血清6-keto-PGF1α、6-keto-PGF1α/TXB2比值、脑组织匀浆c AMP、p-CREB明显升高(P<0.05),且呈剂量依赖性。结论莪术二酮对脑缺血再灌注损伤小鼠认知功能及神经功能有较好的保护作用,其机制可能改善微循环障碍以及激活c AMP/CREB/BDNF信号通路有关。

Objective To investigate the protective effects of curdione on cognitive and neurological function in mice with cerebral ischemia-reperfusion injury.Methods A middle cerebral artery occlusion mouse model was developed using middle cerebral artery embolization(equivalent normal saline;model group;20).Mice received the following treatments:low-molecular-weight heparin sodium[1 mg/(kg·d);HS group;20],low-dose curdione[20 mg/(kg·d);CD-L group;20]or high-dose curdione[60 mg/(kg·d);CD-H group;20].We observed changes in behavioral evaluation,Morris water maze,cerebral infarction volume and cerebral water content,and measured the content of 6-keto prostaglandin F1α(6-keto PGF1α),thromboxane B2(TXB2),6-keto-PGF1α/TXB2 in serum,and c AMP and p-CREB in brain homogenates.Results Compared with the sham operation group,the escape latency in the model group was significantly increased.Number of passes through the platform was obviously reduced(P<0.01).Behavioral evaluation,cerebral infarction volume,and content of cerebral water(%)and TXB2(pg/m L)were obviously increased.The content of6-keto-PGF1α,6-keto-PGF1α/TXB2 ratios,c AMP and p-CREB were all significantly decreased(P<0.01).Compared with the model group,the escape latency in the CD-L and CD-H group was significantly decreased.The numbers of passing through the platform were obviously increased(P<0.05).Behavioral evaluation,cerebral infarction volume,the content of cerebral water and TXB2 were obviously decreased.The content of 6-keto-PGF1α,6-keto-PGF1α/TXB2 ratios,c AMP and p-CREB were significantly decreased(P<0.05),and appeared dose-dependent.Conclusions Curdione had a protective effect on cognitive function and neurological function in mice with cerebral ischemia-reperfusion injury.Its mechanism may be related to the reduction of TXB2,the increment of 6-keto-PGF1α,6-keto-PGF1α/TXB2 ratio,c AMP and p-CREB,thereby improving microcirculation disorders in cerebral ischemia reperfusion injury in a manner involving activation of the c AMP/CREB/BDNF signaling pathway.