丹参川芎嗪注射液对阿尔茨海默症小鼠学习记忆能力及脑内炎性因子、Tau蛋白表达的影响  

Effects of Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection on learning/memory abilities and the expression of inflammatory factors and Tau protein in brain tissue of Alzheimer’s mice

作　　者：姜冉 李慧明 李赞 陈晓燕 丁嘉科 陈永衡[1] JIANG Ran;LI Huiming;LI Zan;CHEN Xiaoyan;DING Jiake;CHEN Yongheng(Changsha Medical College, Changsha 410219, Hunan, China)

机构地区：[1]长沙医学院,湖南长沙410219

出　　处：《现代中西医结合杂志》2022年第6期737-742,779,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：2019年国家级大学生创新创业训练计划项目(201910823055)。

摘　　要：目的探究不同浓度的丹参川芎嗪注射液对阿尔茨海默症(AD)小鼠学习记忆能力及脑组织内炎性因子、Tau蛋白表达的影响。方法采用随机数字表将48只小鼠随机分为空白组、模型组、盐酸多奈哌齐组及丹参川芎嗪低、中、高剂量组,每组8只。除空白组外,其余组均采用单侧海马CA1区注射Aβ25-35方法构建AD模型。建模7d后,盐酸多奈哌齐组给予盐酸多奈哌齐1.3 mL/kg腹腔注射,丹参川芎嗪低、中、高剂量组分别给予丹参川芎嗪注射液0.7 mL/kg、1.3 mL/kg、2.6 mL/kg腹腔注射,空白组、模型组给予生理盐水腹腔注射,均1次/d,连续4周。采用Morris水迷宫实验和新物体识别实验检测小鼠学习记忆和识别记忆能力,HE染色观察小鼠海马组织病理变化,ELISA法检测小鼠脑组织中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)表达水平,免疫组化法和Western blot法检测脑组织中磷酸化Tau蛋白(p-Tau)情况。结果定向航行实验:模型组小鼠第2~5天的逃避潜伏期均明显长于空白组(P均<0.05),盐酸多奈哌齐组和丹参川芎嗪高剂量组均明显短于模型组(P均<0.05)。空间探索实验:模型组小鼠穿越平台次数明显少于空白组(P<0.05),目标象限停留时间明显短于空白组(P<0.05);盐酸多奈哌齐组和丹参川芎嗪中、高剂量组穿越平台次数均明显多于模型组(P均<0.05),目标象限停留时间均明显长于模型组(P均<0.05)。与空白组比较,模型组小鼠新异物体识别实验中探索时间明显延长(P<0.05),偏爱指数明显降低(P<0.05);与模型组比较,盐酸多奈哌齐组和丹参川芎嗪中、高剂量组探索时间均明显缩短(P均<0.05),偏爱指数明显均明显增高(P均<0.05)。与空白组比较,模型组小鼠海马区神经元数量明显减少(P<0.05),脑组织中IL-1β、TNF-α表达量和p-Tau蛋白表达IOD值、p-Tau蛋白相对表达量均明显增高(P均<0.05);与模型组比较,盐酸多奈哌齐组和丹参川芎Objective It is to explore the effects of different concentrations of Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection(SLI)on the learning and memory ability of Alzheimer’s disease(AD)mice and the expression of inflammatory factors and Tau protein in brain tissue.Methods A total of 48 mice were randomly divided into blank group,model group,dopezil hydrochloride group and SLI low,medium and high dose groups by a random number table,with 8 mice in each group.Except for the blank group,AD models were constructed by unilateral injection of Aβ25-35 in the CA1 region of the hippocampus in the other groups.After 7 days of modeling,the dopezil hydrochloride group was given intraperitoneal injection of dopezil hydrochloride 1.3 mL/kg,and the low-dose,medium-dose and high-dose SLI groups were respectively given 0.7 mL/kg,1.3 mL/kg and 2.6 mL/kg SLI by intraperitoneal injection,the blank group and model group were intraperitoneally injected with normal saline,all once per day,continuously treated for 4 weeks.The learning and memory ability and recognition and memory ability of the mice were detected by Morris water maze test and novel object recognition test.The pathological changes of mouse hippocampus was observed by HE staining.The expression level of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)in cerebral tissue was detected by ELISA method,the expression of phosphorylated Tau protein(p-Tau)in brain tissue was detected by immunohistochemistry and Western blot.Results Directional navigation experiment:the escape latency of the mice in the model group on the 2nd to 5th day was significantly longer than that in the blank group(all P<0.05),and the dopezil hydrochloride group and the high-dose SLI group were significantly shorter than the model group(all P<0.05).Space exploration experiment:the times of crossing the platform of the mice in the model group was significantly less than that in the blank group(P<0.05),and the staying time in the target quadrant was significantly shorter than that in

关 键 词：阿尔茨海默症 丹参川芎嗪注射液 炎性反应 小鼠 TAU蛋白 

分 类 号：R-332[医药卫生]