首页|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

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

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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鼠脑组织中SOD含量均明显增高(P均<0.05).结论 同仁牛黄清心丸能够提高血管性认知障碍大鼠的学习记忆能力,其可能通过改善胆碱能系统功能、抗氧化应激、减轻炎症反应而发挥脑保护作用.
Effects and Mechanism of Tongren Niuhuang Qingxin Pills on learning and memory ability of rats with vascular cognitive impairment
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 liga-ted.The remaining rats were used to establish vascular cognitive impairment models by ligating bilateral common carotid ar-teries.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 nimo-dipine 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 choliner-gic 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 significantly increased(both P<0.05),and the number of times crossed the original platform of the rats in the high-dose group of Tongren Niuhuang Qingxin Pill was signif-icantly increased(P<0.05).Compared with the sham operation group,the level of AD7c-NTP in cerebrospinal fluid and the contents of AchE,MDA,IL-6,TNF-α in brain tissue of the rats in the model group were significantly increased(all P<0.05),while the cotent of SOD in brain tissue was significantly decreased(P<0.05).Compared with the model group,the levels of AD7c-NTP in cerebrospinal fluid and the content of AchE in brain tissue of rats in the nimodipine group and high-dose group of Tongren Niuhuang Qingxin Pill,the level of AD7c-NTP in cerebrospinal fluid of rats in the low-dose group of Tongren Niuhuang Qingxin Pill,the content of AchE in brain tissue of rats in the medium dose group of Tongren Niuhuang Qingxin Pill,and the contents of MDA,IL-6,and TNF-α in brain tissue of rats in the nimodipine group and Ton-gren Niuhuang Qingxin Pill groups were significantly reduced(all P<0.05),while the contents of SOD in brain tissue of rats in the Nimodipine group and Tongren Niuhuang Qingxin Pill groups were significantly increased(all P<0.05).Con-clusion Tongren Niuhuang Qingxin Pills could improve the learning and memory abilities of rats with vascular cognitive im-pairment.It might play neuroprotective effects by improving cholinergic system function,antioxidant stress,and reducing inflammatory reactions.

Tongren Niuhuang Qingxin Pillsvascular cognitive impairmentinflammatory factorsoxidative stresscholinergic system

陈霞、张思玉、刘丹、朱晓光、李晋生

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北京同仁堂股份有限公司科学研究所,北京 100079

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

北京市中医药科技发展基金项目

BJZYYB-2023-51

2024

现代中西医结合杂志
中国中西医结合学会河北分会,中华中医药学会

现代中西医结合杂志

CSTPCD
影响因子:1.775
ISSN:1008-8849
年,卷(期):2024.33(15)