Shouwu is a traditional Chinese medicine(TCM)with neuroprotective effect.Shouwu Yizhi decoction(SYD)was designed based on TCM theory.However,little is known about the roles of SYD in Vascular dementia(Va D).The presen...Shouwu is a traditional Chinese medicine(TCM)with neuroprotective effect.Shouwu Yizhi decoction(SYD)was designed based on TCM theory.However,little is known about the roles of SYD in Vascular dementia(Va D).The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion(I/R)rat model to induce Va D.SYD administration(54 mg·kg^(-1))for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion(MCAO)rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test.Moreover,SYD decreased neuron damage-induced cell death and ameliorated the ultrastructure of endothelial cells in the MCAO rats,thereby alleviating Va D.Mechanistically,SYD caused increases in the expression of vascular endothelial growth factor(VEGF),CD34 and CD31,compared with the MCAO rats in coronal hippocampus.Simultaneously,the expression level of mi R-210 was elevated significantly after SYD administration,compared with the vehicle rats(P<0.01).The expression of Notch 4 at both m RNA and protein levels was upregulated remarkably along with the notably downregulated DLL4 expression under SYD administration compared with the vehicle rats(P<0.05).Overall,the above results indicated that SYD promoted angiogenesis by upregulating VEGF-induced mi R210 expression to activate Notch pathway,and further alleviated neuron damage and ameliorated the ultrastructure of endothelial cells in the MCAO rats,ultimately enhancing the cognition and memory of MCAO rats.Therefore,our findings preliminarily identified the effect and the mechanism of action for SYD on Va D in rats.SYD could be a potential candidate in treatment of Va D.展开更多
目的:通过观察醒神开窍针刺法配合益智饮对VD大鼠学习记忆能力和海马组织细胞凋亡相关因子表达的影响,以期从调控海马组织细胞凋亡角度揭示其作用机制。方法:将成年SD大鼠通过随机数字表分为假手术组、模型组、针刺组、中药组、针药结...目的:通过观察醒神开窍针刺法配合益智饮对VD大鼠学习记忆能力和海马组织细胞凋亡相关因子表达的影响,以期从调控海马组织细胞凋亡角度揭示其作用机制。方法:将成年SD大鼠通过随机数字表分为假手术组、模型组、针刺组、中药组、针药结合组和西药组,每组6只。采用线栓法制成大鼠大脑中动脉梗塞血管性痴呆模型。针刺组给予醒神开窍法针刺治疗,每日1次,每次30 min,共治疗8周;中药组给予中药益智饮灌胃治疗,每日1次,每次2 m L;针药结合组同时给予针刺和中药治疗,方法同前;西药组给予盐酸多奈哌齐口服,疗程同前。采用避暗法和穿梭箱法进行学习记忆能力测试;采用免疫组化方法观察大鼠海马神经元Bcl-2和Bax蛋白的表达。结果:避暗法和穿梭箱法结果表明,模型组大鼠潜伏期缩短,错误次数和电击时间增多,与假手术组相比具有显著差异(P<0.05);针刺组、中药组、针药组和西药组VD大鼠潜伏期有所延长,错误次数和电击时间也有所减少,与模型组相比,差异具有统计学意义(P<0.05)。针药组大鼠潜伏期显著延长,错误次数和电击次数均明显减少,与针刺组、中药组和西药组相比,疗效更加显著(P<0.05)。免疫组化检测结果显示,模型组Bax蛋白表达阳性细胞数增加,Bcl-2阳性细胞数降低,与假手术组比较具有显著差异(P<0.05)。与模型组相比,治疗后针刺组、中药组、针药组和药物组Bax的表达降低,Bcl-2的表达增加,差异显著(P<0.05)。与针刺组、中药组和药物组比较,治疗后针药组Bax的表达降低,Bcl-2的表达增加,差异显著(P<0.05)。结论:针刺配合益智饮治疗能够显著改善血管性痴呆大鼠学习认知功能,其作用机制可能是通过上调Bcl-2,下调Bax蛋白表达,从而抑制神经细胞凋亡发挥作用。展开更多
基金supported by the National Natural Science Foundation of China(Nos.81302940,81373670 and 30873323)the Natural Science Foundation of Shandong Province(ZR2015PH046,Y2005C43)+3 种基金Science and Technology Development Grant of the State Administration of TCM of Shandong(2011-192,2015-286,2013-216)Family Planning Committee of Shandong Province([2014]14)the Primary Research&Development Plan of Shandong Province(2016GSF202016)the Innovation Project of Shandong Academy of Medical Sciences
文摘Shouwu is a traditional Chinese medicine(TCM)with neuroprotective effect.Shouwu Yizhi decoction(SYD)was designed based on TCM theory.However,little is known about the roles of SYD in Vascular dementia(Va D).The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion(I/R)rat model to induce Va D.SYD administration(54 mg·kg^(-1))for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion(MCAO)rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test.Moreover,SYD decreased neuron damage-induced cell death and ameliorated the ultrastructure of endothelial cells in the MCAO rats,thereby alleviating Va D.Mechanistically,SYD caused increases in the expression of vascular endothelial growth factor(VEGF),CD34 and CD31,compared with the MCAO rats in coronal hippocampus.Simultaneously,the expression level of mi R-210 was elevated significantly after SYD administration,compared with the vehicle rats(P<0.01).The expression of Notch 4 at both m RNA and protein levels was upregulated remarkably along with the notably downregulated DLL4 expression under SYD administration compared with the vehicle rats(P<0.05).Overall,the above results indicated that SYD promoted angiogenesis by upregulating VEGF-induced mi R210 expression to activate Notch pathway,and further alleviated neuron damage and ameliorated the ultrastructure of endothelial cells in the MCAO rats,ultimately enhancing the cognition and memory of MCAO rats.Therefore,our findings preliminarily identified the effect and the mechanism of action for SYD on Va D in rats.SYD could be a potential candidate in treatment of Va D.
文摘目的:通过观察醒神开窍针刺法配合益智饮对VD大鼠学习记忆能力和海马组织细胞凋亡相关因子表达的影响,以期从调控海马组织细胞凋亡角度揭示其作用机制。方法:将成年SD大鼠通过随机数字表分为假手术组、模型组、针刺组、中药组、针药结合组和西药组,每组6只。采用线栓法制成大鼠大脑中动脉梗塞血管性痴呆模型。针刺组给予醒神开窍法针刺治疗,每日1次,每次30 min,共治疗8周;中药组给予中药益智饮灌胃治疗,每日1次,每次2 m L;针药结合组同时给予针刺和中药治疗,方法同前;西药组给予盐酸多奈哌齐口服,疗程同前。采用避暗法和穿梭箱法进行学习记忆能力测试;采用免疫组化方法观察大鼠海马神经元Bcl-2和Bax蛋白的表达。结果:避暗法和穿梭箱法结果表明,模型组大鼠潜伏期缩短,错误次数和电击时间增多,与假手术组相比具有显著差异(P<0.05);针刺组、中药组、针药组和西药组VD大鼠潜伏期有所延长,错误次数和电击时间也有所减少,与模型组相比,差异具有统计学意义(P<0.05)。针药组大鼠潜伏期显著延长,错误次数和电击次数均明显减少,与针刺组、中药组和西药组相比,疗效更加显著(P<0.05)。免疫组化检测结果显示,模型组Bax蛋白表达阳性细胞数增加,Bcl-2阳性细胞数降低,与假手术组比较具有显著差异(P<0.05)。与模型组相比,治疗后针刺组、中药组、针药组和药物组Bax的表达降低,Bcl-2的表达增加,差异显著(P<0.05)。与针刺组、中药组和药物组比较,治疗后针药组Bax的表达降低,Bcl-2的表达增加,差异显著(P<0.05)。结论:针刺配合益智饮治疗能够显著改善血管性痴呆大鼠学习认知功能,其作用机制可能是通过上调Bcl-2,下调Bax蛋白表达,从而抑制神经细胞凋亡发挥作用。
