Effect of Modified Shuyuwan on Neuroinflammation in APP/PS1 Dementia Mice Based on Nlrp3/ASC/Caspase-1 Signaling Pathway
10.13422/j.cnki.syfjx.20210339
- VernacularTitle:基于Nlrp3/ASC/Caspase-1通路探讨加减薯蓣丸对APP/PS1痴呆小鼠神经炎症的影响
- Author:
Xiao-yan WANG
1
;
Zi-hu TAN
1
;
Xiao-ming YU
1
;
Wei WANG
1
;
He YU
1
;
Qi TANG
1
;
Min XIAO
1
Author Information
1. Hubei University of Chinese Medicine，Wuhan 430065，China
- Publication Type:Research Article
- Keywords:
Modified Shuyuwan;
amyloid precursor protein/presenilin 1（APP/PS1）;
NOD-like receptor 3（Nlrp3）;
inflammation;
microglia
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(3):8-14
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of modified Shuyuwan in amyloid precursor protein/ presenilin 1 （APP/PS1） dementia mice on cognitive and memory impairment and to explore its mechanism. Method:The 40 APP/PS1 mice were divided into model group （given Physiological saline）， low and high-dose modified Shuyuwan （14，64 g·kg-1）group， and donepezil group （1 mg·kg-1） and 10 wild mice were set as the blank control group （given Physiological saline）. All of the mice were administered intragastrically for 35 days. The memory and space exploration ability of mice was detected by Morris water maze， the morphology of mouse hippocampal neurons were observed by Nissl staining. The deposition of β amyloid 1-42（Aβ1-42） in mouse hippocampus was detected by immunohistochemistry， and the expression of ionized calcium-binding adapter molecule 1（Iba1）， a marker of hippocampal microglia （MG） and Nitric oxide synthase（iNOS）， a marker of actived MG， were detected by immunofluorescence. The protein expression of NLR family pyrin domain containing 3（Nlrp3）， Apoptosis-associated speck-like protein containing a Caspase-recruitment domain （ASC）， cysteine protease-1（Caspase-1）and interleukin-1 beta （IL-1β） were detected by Western blot， and the expression of IL-1β， tumor necrosis factor-α（TNF-α）and interleukin-18 （IL-18） mRNA were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the blank control group， the memory and space exploration ability of the model group were significantly reduced （P<0.05）， the number of hippocampal neurons decreased， the deposition of Aβ1-42 increased， the markers of actived MG Iba1，iNOS increased， the protein expression of Nlrp3， ASC， Caspase-1， IL-1β increased significantly （P<0.05）， and the mRNA expression of IL-1β， IL-18， and TNF-α increased significantly （P<0.05）. Compared with model group， the Chinese medicine group can improve the APP/PS1 mice's space exploration ability and memory ability （P<0.05）， increase the number of hippocampal neurons， reduce Aβ1-42 deposition， reduce the activation of MG， and reduce the protein expression of Nlrp3， ASC， Caspase-1 and IL-1β （P<0.05）， and reduced the expression of IL-1β mRNA （P<0.05）. Conclusion:Modified Shuyuwan can reduce the expression of IL-1β and other inflammatory factors in the hippocampus of APP/PS1 mice by inhibiting the Nlrp3/ASC/Caspase-1 pathway， and relieve nerve inflammation and pathological injury of AD.
