同仁牛黄清心丸对血管性认知障碍大鼠学习记忆能力的影响及机制  

Effects and Mechanism of Tongren Niuhuang Qingxin Pills on learning and memory ability of rats with vascular cognitive impairment

作　　者：陈霞[1] 张思玉[1] 刘丹[1] 朱晓光[1] 李晋生[1] CHEN Xia;ZHANG Siyu;LIU Dan;ZHU Xiaoguang;LI Jinsheng(Science Research Institute of Beijing TRT Limited Co Ltd.,Beijing 100079,China)

机构地区：[1]北京同仁堂股份有限公司科学研究所,北京100079

出　　处：《现代中西医结合杂志》2024年第15期2078-2082,2087,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：北京市中医药科技发展基金项目(BJZYYB-2023-51)。

摘　　要：目的探讨同仁牛黄清心丸对血管性认知障碍大鼠学习记忆能力的影响及可能作用机制。方法取雄性Wistar大鼠90只,随机取11只作为假手术组,暴露但不结扎双侧颈总动脉;其余大鼠均采用结扎双侧颈总动脉方法建立血管性认知障碍模型。将造模组大鼠随机分为模型组、尼莫地平组及同仁牛黄清心丸高、中、低剂量组,每组11只。尼莫地平组给予尼莫地平12 mg/kg灌胃,同仁牛黄清心丸高、中、低剂量组分别给予2.4 g/kg、1.2 g/kg、0.6 g/kg同仁牛黄清心丸灌胃,模型组和假手术组给予等体积纯化水灌胃,均1次/d。连续灌胃4周后,采用Morris水迷宫实验测试大鼠学习记忆能力(记录测试象限内游泳路径长度和穿越原平台次数);处死大鼠,测定脑脊液中阿尔茨海默相关神经丝蛋白(AD7c-NTP)水平和脑组织中胆碱能指标[乙酰胆碱酯酶(AchE)]、氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)]、炎症指标[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)]含量。结果与假手术组比较,模型组大鼠测试象限内游泳路径长度明显缩短(P<0.05),穿越原平台次数明显减少(P<0.05);与模型组比较,尼莫地平组和同仁牛黄清心丸高、低剂量组大鼠测试象限内游泳路径长度明显增加(P均<0.05),同仁牛黄清心丸高剂量组大鼠穿越原平台次数明显增多(P<0.05)。与假手术组比较,模型组大鼠脑脊液中AD7c-NTP含量和脑组织中AchE、MDA、IL-6、TNF-α含量均明显升高(P均<0.05),脑组织中SOD含量明显降低(P<0.05);与模型组比较,尼莫地平组和同仁牛黄清心丸高剂量组大鼠脑脊液中AD7c-NTP含量和脑组织中AchE含量、同仁牛黄清心丸低剂量组大鼠脑脊液中AD7c-NTP含量、同仁牛黄清心丸中剂量组大鼠脑组织中AchE含量及尼莫地平组和同仁牛黄清心丸各组大鼠脑组织中MDA、IL-6和TNF-α含量均明显降低(P均<0.05),尼莫地平组和同仁牛黄清心丸各组大Objective It is to explore the effect and mechanism of Tongren Niuhuang Qingxin Pills on the learning and memory abilities of rats with vascular cognitive impairment.Methods Ninety male Wistar rats were selected,in which 11 rats were randomly selected as the sham operation group,their bilateral common carotid arteries were exposed but not ligated.The remaining rats were used to establish vascular cognitive impairment models by ligating bilateral common carotid arteries.The modeled rats were randomly divided into model group,nifedipine group,and high,medium,and low dose groups of Tongren Niuhuang Qingxin Pill,with 11 rats in each group.The nimodipine group was given 12 mg/kg of nimodipine by gavage,while the high,medium,and low dose groups of Tongren Niuhuang Qingxin Pill were given 2.4 g/kg,1.2 g/kg,and 0.6 g/kg of Tongren Niuhuang Qingxin Pill by gavage,respectively.The model group and sham operation group were given equal volumes of purified water by gavage,all once daily.After continuous intragastric administration for 4 weeks,the learning and memory abilities of rats were tested by Morris water maze test(recording the length of swimming paths within the test quadrant and the number of times crossed the original platform).Then the rats were executed to detect the level of Alzheimer's associated neuronal thread protein(AD7c-NTP)in cerebrospinal fluid and the contents of cholinergic markers[acetylcholinesterase(AchE)],oxidative stress markers[superoxide dismutase(SOD),malondialdehyde(MDA)],inflammatory markers[tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6)]in brain tissue.Results Compared with the sham operation group,the swimming path length in the test quadrant of the rats in the model group was significantly shortened(P<0.05),and the number of times crossed the original platform was significantly reduced(P<0.05).Compared with the model group,the swimming path length in the test quadrant of the rats in the Nimodipine group and the high and low dose groups of Tongren Niuhuang Qingxin Pill were signific

关 键 词：同仁牛黄清心丸 血管性认知障碍 炎症因子 氧化应激 胆碱能系统 

分 类 号：R-332[医药卫生]