摘要
目的 研究参枣健脑口服液(SZJN)对阿尔茨海默病(AD)模型小鼠的神经保护作用及机制。方法 将小鼠随机分为假手术组、模型组、盐酸多奈哌齐片组(0.65 mg/kg)和SZJN低、中、高剂量组(0.3、1.5、7.5 g/kg,以生药量计),每组12只,雌雄各半。各组小鼠灌胃相应药物(假手术组和模型组小鼠灌胃等体积水),每日2次,连续28 d。在给药第15天时,采用侧脑室注射β-淀粉样蛋白1-42(Aβ1-42)联合腹腔注射氢溴酸东莨菪碱复制AD小鼠模型。采用Morris水迷宫实验检测小鼠的学习记忆能力;采用HE染色和Nissl染色检测小鼠脑组织病理学变化;检测小鼠脑组织中丙二醛(MDA)和超氧化物歧化酶(SOD)的水平;采用Western blot法检测小鼠海马组织中环磷酸腺苷反应元件结合蛋白(CREB)的磷酸化水平和脑源性神经营养因子(BDNF)的蛋白表达水平。结果 与假手术组比较,模型组小鼠逃避潜伏期显著延长,穿越平台次数和目标象限停留时间百分比显著减少(P<0.01);脑组织中SOD水平以及海马组织中CREB蛋白磷酸化水平和BDNF蛋白表达水平均显著降低(P<0.01),MDA水平显著升高(P<0.01);海马CA1区和皮层组织中神经细胞数量明显减少、排列杂乱且间隙大,细胞核形状不规则且深染,尼氏体模糊不清、排列疏松、数量减少。与模型组比较,SZJN各剂量组小鼠逃避潜伏期显著缩短,穿越平台次数和目标象限停留时间百分比显著增加(P<0.01);SZJN高剂量组小鼠脑组织中上述指标水平均显著逆转(P<0.01),脑组织病理损伤均得到改善。结论 SZJN可显著改善AD模型小鼠的学习记忆能力,减轻脑组织病理损伤和氧化应激,其作用机制可能与激活CREB/BDNF信号通路有关。
OBJECTIVE To study the neuroprotective effects of Shenzao jiannao oral liquid(SZJN)on Alzheimer’s disease(AD)model mice and its mechanism. METHODS The mice were randomly divided into sham operation group,model group,Donepezil hydrochloride tablet group(0.65 mg/kg),SZJN low-dose,medium-dose and high-dose groups(0.3,1.5 and 7.5 g/kg,calculated by crude drug quantity),with 12 mice in each group,half male and half female. Each group was given relevant medicine(intragastric administration of water at constant volume in sham operation group and model group),twice a day,for consecutive 28 d. On the 15th day of administration,intracerebroventricular injection of β-amyloid 1-42(A β1-42)combined with intraperitoneal injection of scopolamine hydrobromide were used to induce AD model. Morris water maze was used to detect the learning and memory ability of mice. HE staining and Nissl staining were used to evaluate the pathological changes of brain tissue in mice. The levels of MDA and SOD in brain tissue of mice were detected. The phosphorylation level of cyclic adenosine monophosphate response element binding protein(CREB) and expression of brain-derived neurotrophic factor(BDNF) in hippocampal tissues were detected by Western blot. RESULTS Compared with sham operation group,the escape latency of the model group was significantly prolonged,and the number of crossing the platform and the percentage of residence time in the target quadrant were significantly reduced(P<0.01). The level of SOD in brain tissue,the phosphorylation level of CREB and the expression level of BDNF in hippocampus decreased significantly(P<0.01),while the level of MDA increased significantly(P<0.01). In hippocampal CA1 area and cortical tissue,nerve cells showed significantly decreased number,the disordered arrangement and large gap;the shape of nucleus was irregular and deeply stained,and Nissl body was blurred,loosely arranged and the number decreased. Compared with model group,the escape latency of mice in each dose group of SZJN was significantly shortened,and the times of crossing the platform and the percentage of residence time in the target quadrant were significantly increased(P<0.01). Above indexes of brain tissue in mice were reversed significantly in SZJN high-dose group(P<0.01),and pathological damage of brain tissue was improved. CONCLUSIONS SZJN can significantly improve the learning and memory ability of AD model mice,and alleviate the pathological injury and oxidative stress of brain tissue,which may be related to the activation of CREB/BDNF signaling pathway.
作者
金衔
陈吉聪
辛玉英
肖洪贺
李妍
邓艳
杨静娴
JIN Xian;CHEN Jicong;XIN Yuying;XIAO Honghe;LI Yan;DENG Yan;YANG Jingxian(Dept.of Rehabilitation,Dalian Central Hospital,Liaoning Dalian 116000,China;School of Pharmacy,Liaoning University of Traditional Chinese Medicine,Liaoning Dalian 116600,China)
出处
《中国药房》
CAS
北大核心
2022年第7期836-841,847,共7页
China Pharmacy
基金
大连市科技创新基金项目(No.2018J13SN126)。
