淫羊藿黄酮对慢性脑缺血低灌注致大鼠脑白质病变的影响

Epimedium flavonoids improve white matter lesions induced by chronic cerebral hypoperfusion in rats

目的研究淫羊藿黄酮(epimedium flavonoids,EF)对慢性脑缺血低灌注损伤模型大鼠脑白质病变的影响。方法采用双侧颈总动脉结扎(permanent bilateral common carotidartery occlusion,2VO)法制备慢性脑缺血低灌注大鼠模型,采用数字表法将大鼠随机分为5组:假手术组,模型组,EF中、高剂量(100、200 mg/kg)给药组,阳性对照药尼莫地平组,于2VO术后24 h开始灌胃给药,一天1次,连续给药6周。采用新物体识别实验评价各组大鼠认知功能的变化,磁共振观察各组大鼠脑白质损伤变化,坚牢蓝(luxol fast blue,LFB)染色观察各组大鼠胼胝体部位髓鞘结构变化。结果新物体实验结果中模型组大鼠分辨指数较假手术组大鼠显著降低,而与模型组相比,各给药组大鼠的分辨指数明显升高。磁共振结果显示模型组大鼠脑白质胼胝体及视束部位纤维束受损,EF给药能明显保护神经纤维的完整性,减轻2VO术后脑白质损伤。LFB染色结果显示,长期慢性脑缺血低灌注引起大鼠胼胝体部位髓鞘结构紊乱,而EF给药后可显著减轻髓鞘脱失现象。结论EF可减少2VO术后大鼠脑白质髓鞘结构异常,减轻脑白质损伤,进而改善模型大鼠认知功能障碍。

Objective To investigate the effects of epimedium flavonoids(EF)on white matter lesions induced by chronic cerebral hypoperfusion in rats.Methods Male SD rats were subjected to permanent bilateral common carotid artery ligation(2VO)surgery.All rats were randomly divided into 5 groups:sham group,model group,EF 100 mg/kg group,EF 200 mg/kg group and nimodipine group.Drugs were administered intragastrically at 24 h after surgery for 6 weeks.The new object recognition test was used to assess the spatial memory recognition ability of rats.Diffusion tensor imaging was used to detect the changes of microstructure and fractional anisotropy coefficient(FA),apparent diffusion coefficient(ADC),axial diffusion coefficient(AD)and radial diffusivity coefficient(RD)in corpus callosum and optic tract of white matter in 2VO model rats.White matter structure was also observed with luxol fast blue(LFB)staining.Results After 2VO surgery the discrimination index in the new object recognition test significantly decreased,the value of FA decreased,and the RD value increased,indicating the damage of white matter in 2VO rats.In addition,the grading score of LFB staining was significantly downregulated.While treatment with EF increased the discrimination index,reduced the microstructure damage of corpus callosum and optic tract,protected the integrity of nerve fibers,decreased the grading score of LFB staining in corpus callosum of 2VO model rats,alleviated the demyelination of myelin.Conclusion EF treatment could reduce the structural abnormalities of the myelin sheath in rats after 2VO operation,alleviate the lesion of white matter,and improve the learning and memory dysfunction in 2VO rats.