Mechanism of Kaixin San inhibiting neuroinflammation in Alzheimer's disease mice by regulating NLRP3/Caspase-1/GSDMD signaling pathway
Objective:To explore the neuroprotective effect of Kaixin San on Alzheimer's disease(AD)mice and its effect on NLRP3/Caspase-1/GSDMD signaling pathway.Methods:Forty mice were randomly divided into 4 groups:normal group,model group,Kaixin San group and Donepezil group,with 10 mice in each group.After 3 months intervention,Morris water maze was used to test the learning and memory ability of mice,and ELISA was used to detect the expression levels of IL-18,IL-1 β and A β 1-42 in serum.Nissal and IHC were used to observe the pathological changes and the expression of IL-18 and IL-1 β in hippocampal CA1 region.The protein expression levels of NLRP3,Caspase-l,GSDMD,IL-1 β and IL-18 in hippocampus were detected by Western Blot.Results:Compared with the normal group,the escape latency of the model group mice was significantly prolonged,the number of crossing platforms and the target quadrant residence time were significantly reduced(P＜0.01),and the serum levels of A β 142,IL-18,IL-1 β significantly increased(P＜0.01);The number of Nissl bodies in the hippocampus decreased significantly,NLRP3,Caspase-1,GSDMD,IL-1 β,IL-18 protein expression significantly increased(P＜0.01);Compared with the model group,the escape latency of mice in the Donepezil and Kaixin San groups was significantly shortened,and the number of times they crossed the platform and the target quadrant residence time were significantly prolonged(P＜0.05,P＜0.01),the serum levels of A β 1-42,IL-18 and IL-1 β were significantly decreased(P＜0.05,P＜0.01),the number of Nissl bodies in the hippocampus was increased,and the expression of NLRP3,Caspase-1,GSDMD,IL-1 β and IL-18 was significantly decreased(P＜0.05,P＜0.01).Conclusion:Kaixin San may play a neuroprotective role by regulating NLRP3/Caspase-1/GSDMD signaling pathway to inhibit the activation of inflammasome and inhibit cell coke death.
Alzheimer's diseaseNLRP3 inflammatory corpusclePyroptosisKaixin San
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