智元康颗粒调控SorLA通路改善APP/PS1小鼠学习记忆能力的神经保护作用机制研究OA

Objective To investigate the neuroprotective effect of Zhiyuankang Granule(智 元 康 颗 粒,ZYK)on APP/PS1 mice and explore its mechanism of action in regulating sorting protein-related receptor with A-type repeats(SorLA)to inhibit abnormal hydrolysis of amyloid precursor protein(APP).Methods Learning and memory functions were assessed using the Morris water maze and novel object recognition tests.β-amyloid deposition was detected by Congo red staining,and tangles were examined by glycine silver staining.The expression levels of the SorLA pathway and its downstream molecules were measured via Western blot(WB)and RT-qPCR.Results Compared with the Control group,the Model group showed significant decline in learning and memory abilities and severe neural damage(P<0.01).The mRNA and protein expression levels of SorLA,ADAM10,and GGA3 in the hippocampus were decreased,while those of BACE1,TNF-α,and Iba1 were increased(P<0.01).The protein expression levels of PSD95 and SYN were decreased,and APP expression was increased(P<0.01).Compared with the Model group,both the ZYK group and the Donepezil hydrochloride group exhibited significantly improved learning and cognitive function.Congo red staining and glycine silver staining results indicated notable alleviation of Aβ and Tau pathology as well as neural damage(P<0.05,P<0.01).RT-qPCR and WB analysis revealed that the ZYK group had increased mRNA and protein expression levels of SorLA,ADAM10,and GGA3,decreased levels of BACE1,TNF-α,and Iba1,elevated protein expression of PSD95 and SYN,and reduced APP protein expression(P<0.05,P<0.01).In the Done-pezil group,the expression levels of PSD95,SYN,and GGA3 were increased,while those of APP,BACE1,TNF-α,and Iba1 were decreased(P<0.05,P<0.01);however,the expression levels of SorLA and ADAM10 showed no statistical significance(P>0.05).Conclusion ZYK can inhibit abnormal APP hydrolysis by regulating SorLA,thereby mitigating neuroinflammation and exerting a neuro-protective effect.