知母-黄芪散复方通过TNF-α/JNK通路改善阿尔茨海默症大鼠认知障碍的研究  

Effects of Drug-couple Recipe of Zhimu-Huangqi Powder on Improving Cognitive Disorder of Alzheimer's Disease Rats by Regulating TNF-α/JNK Signaling Pathway

作　　者：刘静[1] 高颖[1] 杨利[1] 丁嘉华[1] 高英[1] 周欣欣[1] 李卫民[1] 

机构地区：[1]广州中医药大学中药学院,广东广州510006

出　　处：《中药新药与临床药理》2017年第3期320-326,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81373775;81473439;81273897)

摘　　要：目的研究知母-黄芪散复方通过TNF-α/JNK通路改善阿尔茨海默症大鼠认知障碍的作用机制及其药效初探。方法取雄性SD大鼠50只,根据基础血糖和体质量水平随机分为5组,每组10只,即正常组,模型组,知母组,黄芪散组,知母-黄芪散组;采用腹腔注射链脲佐菌素(STZ)联合喂食高脂饲料+AlCL_3灌胃的方法建立模型,连续灌胃20周。分别在给药第8、16周时,测定空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)水平;结合Barnes迷宫检测大鼠的认知状况;给药20周时,测定血浆TNF-α、P-JNK、Aβ_(1-42)蛋白及INS水平,结合Morris水迷宫检测大鼠的认知能力;给药20周结束,解剖保存大鼠脑组织、海马组织作病理形态学观察。结果给药8周、16周时,与正常组比较,模型组大鼠空腹血糖(FPG)、TC、TG水平均显著性升高(P<0.05,P<0.01);与模型组比较,知母-黄芪散组可有效降低模型大鼠FPG、TC、TG水平(P<0.05);给药20周,与正常组比较,模型组大鼠血浆TNF-α、P-JNK、Aβ_(1-42)水平也明显升高(P<0.01);与模型组比较,经连续给药后,知母组,知母-黄芪散组大鼠血浆TNF-α、P-JNK、Aβ1-42水平均显著降低(P<0.05,P<0.01);行为学实验结果显示,与模型组比较,知母-黄芪散组表现出较显著的改善记忆、认知行为的作用(P<0.05,P<0.01);组织形态学结果显示,正常组大鼠海马CAI区神经元排列整齐,形态规则,着色均匀;与模型组比较,知母组可有效改善大鼠海马组织神经元形态及细胞排列形态,修复神经损伤,大鼠胰腺病理形态改变与海马CAI区神经元病理改变具有一定正相关趋势。结论知母组及知母-黄芪散组不仅降糖效果明显,并且可以通过调节TNF-α/JNK通路改善STZ+高脂饲料+AlCL_3灌胃喂养诱导实验性阿尔茨海默症大鼠认知、记忆能力。Objective To study the effects of the drug-couple Zhimu-Huangqi Powder（Rhizoma Anemarrhenae and Radix Astragalipowder） on cognitive disorder of Alzheimer＇s disease （AD） rats by regulating TNF-α/JNK signaling pathway. Methods Fifty male SD rats were divided into normal group, model group, Zhimu Powder group, Huangqi Powder group, and Zhimu-Huangqi Powder group according to the blood glucose level and body mass. The AF rat model was established by intraperitoneal injection of streptozotocin （STZ） combined with feeding high-fat diet and intragastric administration of AlCl3. The rats were administered with the corresponding medicine for 20 continuous weeks. After administration for 8, 16 weeks, we detected the plasma levels of glucose（GLU）, total cholesterol（TC） and triglyceride （TG）. And Barnes maze was used for the observation of cognitive ability of rats in each group. After administration for 20 weeks, we detected the plasma levels of tumor necrosis factor alpha （TNF-α） , phosphorylated c-Jun N-terminal kinase（P-JNK）, amyloid [3-protein 1-42（A[31-42） and brain insulin（INS） level, and observed the cognitive ability of rats in each group with Morris maze. At the end of week 20, rat brain was isolated for the histopathological inspection of the hippocampus. Results After treatment for 8, 16 weeks, fast plasma glucose（FPG）, TC and TG levels of the model group were significantly increased as compared with the normal group （P 〈 0.05, P 〈 0.01） ; compared with the model group, FPG, TC and TG levels of Zhimu-Huangqi Powder group were significantly decreased （P 〈 0.05 ）. After administration for 20 weeks, the plasma TNF-α, P-JNK and Aβ1-42 levels of the model group were significantly increased as compared with the normal group （P 〈0.01） ; compared with the model group, TNF-α , P-JNK and Aβ1-42 levels of Zhimu Powder group and Zhimu-Huangqi Powder group were significantly decreased （P 〈 0.05, P 〈 0.01 ）. In respect for the behavioral changes, Z

关 键 词：知母 知母-黄芪散 阿尔茨海默病 3型糖尿病 AΒ1-42 TNF-Α P-JNK 

分 类 号：R285.5[医药卫生—中药学]