癫痫清颗粒通过调控NLRP3/Caspase-1通路对阿尔茨海默病小鼠Tau蛋白的影响  

Effects of Dianxianqing Granules on Tau protein in a mouse model of Alzheimer's disease via NLRP3/Caspase-1 pathway

作　　者：夏春鹏 齐越[1] 董笑博 房小楠 李纪彤 黄培池 贾冬[1] 明彩荣[1] XIA Chun-peng;QI Yue;DONG Xiao-bo;FANG Xiao-nan;LI Ji-tong;HUANG Pei-chi;JIA Dong;MING Cai-rong(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Department of General Internal Medicine,The First Hospital Affiliated to Ningbo University,Ningbo 315010,China;Department of Pharmaceutical Engineering,Xuzhou Pharmaceutical Vocational College of Jiangsu Province,Xuzhou 221116,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]宁波大学附属第一医院全科医学科,浙江宁波315010 [3]江苏省徐州医药高等职业学校药学技术系,江苏徐州221116

出　　处：《中成药》2024年第12期3968-3976,共9页Chinese Traditional Patent Medicine

基　　金：徐州市科技项目(KC22134);浙江省教育厅一般项目(ZX2021000605)。

摘　　要：目的 研究癫痫清颗粒对阿尔茨海默病小鼠Tau蛋白的影响。方法 将P301S突变Tau转基因小鼠随机分为模型组、 MCC950组(NLRP3抑制剂,10 mg/kg)、癫痫清颗粒组(12.48 g/kg)、 MCC950+癫痫清颗粒组,另以C57BL/6小鼠为对照组。给药5个月后,通过Y迷宫实验、 Morris水迷宫实验检测小鼠学习记忆能力;HE染色观察脑组织形态学改变;免疫组化法检测脑组织Caspase-1、 GSDMD蛋白表达;免疫荧光法检测脑组织Tau蛋白表达;Western blot法检测脑组织Tau、 p-Tau (ser202)、 p-Tau (thr205)、 NLRP3、 Caspase-1、 IL-1β、 IL-18蛋白表达。结果 与对照组比较,模型组小鼠自发交替反应率和穿越平台次数降低(P<0.05,P<0.01);脑组织海马区形态异常,神经元数目减少;脑组织Caspase-1、 GSDMD阳性表达增加(P<0.05),可见大量的棕黄色颗粒沉积在细胞质中;脑组织海马和皮质部位Tau、 p-Tau (ser202)、 p-Tau (thr205)及NLRP3、 Caspase-1、 IL-1β、 IL-18蛋白表达均升高(P<0.05,P<0.01)。与模型组比较,癫痫清颗粒组小鼠自发交替反应率和穿越平台次数均升高(P<0.05);脑组织结构完整,神经元细胞排列整齐有序;脑组织Caspase-1、 GSDMD阳性表达减少(P<0.05);脑组织Tau、 p-Tau (ser202)、 p-Tau(thr205)及NLRP3、 Caspase-1、 GSDMD、 IL-1β、 IL-18蛋白表达降低(P<0.05,P<0.01)。结论 癫痫清颗粒可能通过调控NLRP3/Caspase-1通路抑制阿尔茨海默病小鼠Tau蛋白表达。AIM To study the effects of Dianxianqing Granules on Tau protein in a mouse model of Alzheimer's disease(AD).METHODS The mice expressing P301S mutant Tau variant were randomly divided into the model group,the MCC950 group( NLRP3 inhibitor,10 mg/kg),the Dianxianqing Granules group(12.48 g/kg),the MCC950+Dianxianqing Granules group,in contrast to the C57BL/6 mice of the control group.After 5 months of administration,the mice had their learning and memory ability tested by Y maze test and Morris water maze test;their cerebral morphological changes observed by HE staining;their cerebral expressions of Caspase-1 and GSDMD proteins detected by immunohistochemical method;their expression of cerebral Tau protein detected by immunofluorescence;and their cerebral expressions of Tau,p-Tau( ser202),p-Tau( thr205),NLRP3,Caspase-1,IL-1β and IL-18 detected by Western blot.RESULTS Compared with the control group,the model group displayed decreased rate of spontaneous alternate reaction and times of crossing platform(P<0.05,P< 0.01);abnormal hippocampal morphology,decreased number of neurons,increased cerebral positive expressions of Caspase-1 and GSDMD(P<0.05);deposition of a large number of brown granules in cytoplasm,and increased protein expressions of Tau,p-Tau(ser202),p-Tau(thr205),NLRP3,Caspase-1,IL-1β and IL-18 in the hippocampus and the cortex(P<0.05,P<0.01).Compared with the model group,the group intervened with Dianxianqing Granules demonstrated both increased rate of spontaneous alternate reaction and times of crossing platform(P<0.05);complete and normal morphology of the brain,a diversity of fine neurons,reduced cerebral positive expressions of Caspase-1 and GSDMD(P< 0.05);and decreased protein expressions of Tau,p-Tau(ser202),p-Tau(thr205),NLRP3,Caspase-1,IL-1β and IL-18 in the hippocampus and the cortex(P<0.05,P<0.01).CONCLUSION Dianxianqing Granules may inhibit Tau protein expression in the mouse model of AD viaNLRP3/Caspase-1 pathway.

关 键 词：癫痫清颗粒 阿尔茨海默病 TAU蛋白 NLRP3/Caspase-1通路 

分 类 号：R285.5[医药卫生—中药学]