水飞蓟宾对阿尔茨海默病模型小鼠炎症反应及NF-κB/NLRP3/Caspase-1通路的影响  

The effect of silibinin on inflammatory response and NF-κB/NLRP3/Caspase-1 signaling pathway in Alzheimer’s disease model mice

作　　者：王瑶[1] 肖东芳 冯超 WANG Yao;XIAO Dong-fang;FENG Chao(Department of Neurology,Tieling Central Hospital,Tieling 112001;Department of Neurology,General Hospital of the Northern Theater Command,Shenyang 110016,China)

机构地区：[1]铁岭市中心医院神经内科,辽宁铁岭112001 [2]北部战区总医院神经内科,辽宁沈阳110016

出　　处：《解剖科学进展》2021年第6期727-731,共5页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(2019-MS-034)。

摘　　要：目的探讨水飞蓟宾对APP/PS1转基因小鼠神经炎症及对NF-κB/NLRP3/Caspase-1信号通路的影响。方法将7月龄APP/PS1小鼠40只,随机分为模型组(model)、水飞蓟宾低剂量组(100 mg/kg)、水飞蓟宾高剂量组(200 mg/kg)及盐酸多奈哌齐组(10 mg/kg),每组10只;另取同龄C57BL/6小鼠作为对照组(control)。Morris水迷宫检测各组小鼠的学习与记忆能力;免疫荧光染色检测各组小鼠海马区GFAP及IBA-1阳性细胞表达情况;ELISA检测各组小鼠海马区IL-6,TNF-α及IL-1β水平;Western blot检测iNOS,COX-2,NF-κB,NLRP3,Caspase-1及IL-1β蛋白表达。结果与模型组相比,水飞蓟宾组小鼠逃避潜伏期明显缩短,单位时间内在原目标象限停留时间延长,穿越平台次数增加,GFAP及IBA-1阳性细胞数量显著降低,IL-6,TNF-α及IL-1β水平明显降低,海马区iNOS及COX-2蛋白表达明显降低,水飞蓟宾显著降低小鼠海马区NF-κB,NLRP3, Caspase-1及IL-1β蛋白的表达(P<0.05)。结论水飞蓟宾抑制APP/PS1转基因小鼠海马区炎症反应,改善学习记忆能力,与调控NF-κB/NLRP3/Caspase-1信号通路相关。Objective To investigate the effects of silibinin on neuroinflammation and NF-κ B/NLRP3/Caspase-1 signaling pathway in APP/PS1 transgenic mice. Methods Forty seven-month-old APP/PS1 mice were randomly averagely divided into model group, silibinin low-dose group(100 mg/kg) group, and a silibinin high-dose group(200 mg/kg) and donepezil hydrochloride group(10 mg/kg DH), the same age C57 BL/6 mice were used as the control group. Morris water maze was used to detect the learning and memory ability, the expression of GFAP and IBA-1 positive cells were detected by immunofluorescence staining. ELISA was used to detect IL-6, TNF-α and IL-1β levels in hippocampus. The expressions of iNOS, COX-2, NF-κB, NLRP3, Caspase-1 and IL-1β were detected by Western blot.Results Compared with the model group, silibinin decreased the escape latency, extended the residence time in the original target quadrant, increased the number of crossing platforms, downregulated the number of GFAP and IBA-1 positive cells and the levels of IL-6, TNF-α, IL-1β, iNOS and COX-2 in hippocampus, Silibinin also significantly reduced the expression levels of NF-κB, NLRP3, Caspase-1 and IL-1β in the hippocampus(P<0.05). Conclusion Silibinin inhibits the inflammatory response in hippocampus of APP/PS1 transgenic mice and improved the ability of learning and memory,which is related to the regulation of NF-κB/NLRP3/caspase-1 signaling pathway.

关 键 词：水飞蓟宾 阿尔茨海默病 炎症反应 NF-B/NLRP3/Caspase-1信号通路 APP/PS1转基因小鼠 

分 类 号：R749.16[医药卫生—神经病学与精神病学]