姜黄素通过激活SIRT1调节脓毒症小鼠模型的认知功能障碍研究

Curcumin regulates cognitive dysfunction in sepsis mice by activating SIRT1

目的:探讨姜黄素对脓毒症小鼠模型认知功能障碍的作用及机制。方法:将小鼠随机分为假手术组,模型组,姜黄素低、中、高剂量组,地塞米松组,SIRT1抑制剂组,高剂量+抑制剂组,每组20只。通过盲肠结扎和穿刺(CLP)诱导小鼠脓毒症,并通过腹腔注射给药。通过旷场实验、莫里斯水迷宫检测小鼠活动探索及学习认知能力,HE染色检测脑损伤,流式细胞术检测神经细胞凋亡率,Elisa检测TNF-α、IL-6和IL-1β含量,试剂盒检测MDA、SOD和CAT水平,蛋白印迹法检测SIRT1、Ac-NF-κB、Ac-FOXO1和Ac-p53表达水平。结果:与模型组相比,姜黄素高剂量组小鼠存活率增加(P<0.01),总行驶距离、站立次数和梳理毛发次数及在目标象限时间和穿越区域的次数均增加(P<0.01),潜伏期时间减少(P<0.01),海马区病理损伤减轻,神经细胞凋亡率减少(P<0.01),IL-6、TNF-α、IL-1β、MDA含量均减少(P<0.01),SOD和CAT活性升高(P<0.01),SIRT1表达上调(P<0.01),Ac-FOXO1、Ac-NF-κB和Ac-p53表达均下调(P<0.01);加入SIRT1抑制剂EX-527逆转了姜黄素对脓毒症小鼠的作用。结论:姜黄素通过激活SIRT1调节脓毒症小鼠模型的认知功能障碍,这与FOXO1、p53和NF-κB的脱乙酰作用密切相关。

Objective:To investigate the effect and mechanism of curcumin on cognitive dysfunction in mouse model of sepsis.Methods:Mice were randomly divided into Sham group,Model group,Curcumin low,medium,high-dose group,dexamethasone group,SIRT1 inhibitor group,and high-dose+inhibitor group,20 rats in each group.Methods:Sepsis was induced by cecal ligation and puncture(CLP)in mice and administered by intraperitoneal injection.Then,the activity exploration and learning cognitive ability of mice were tested by open field experiments and Morris water maze,brain damage detected by HE staining,nerve cell apoptosis rate was detected by flow cytometry,the contents of TNF-α,IL-6 and IL-1βwere detected by Elisa test,MDA,SOD and CAT levels were tested with kits,the expression levels of SIRT1,Ac-NF-κB,Ac-FOXO1 and Ac-p53 were detected by Western blotting.Results:Compared with the Model group,the survival rate of the mice in the Curcumin high-dose group was increased(P<0.01),the total distance traveled,the number of standing and grooming times,and the number of times in the target quadrant and crossing the area were increased(P<0.01),the latency time was reduced(P<0.01),the pathological damage in the hippocampus was reduced,the neuronal apoptosis rate was reduced(P<0.01),TNF-α,IL-1β,MDA content were reduced(P<0.01),SOD and CAT activities were increased(P<0.01),SIRT1 expression was up-regulated(P<0.01),and Ac-FOXO1,Ac-NF-κB,and Ac-p53 expressions were down-regulated(P<0.01).The addition of SIRT1 inhibitor EX-527 reversed the effect of curcumin on sepsis mice.Conclusion:Curcumin regulates cognitive dysfunction in sepsis mice by activating SIRT1.This is related to FOXO1,P53 and NF-κB deacetylation.