Tongqiao Huoxue Decoction Improves Cognitive Function in Alzheimer's Disease Rats byRegulating Caspase-3/GSDME Pathway-Mediated Pyroptosis

doi:10.3870/j.issn.1672-0741.25.04.028

Abstract

Abstract: Objective To investigate the mechanism by which Tongqiao Huoxue decoction(TQHXD) regulates the Caspase-3/Gasdermin E(GSDME)pathway-mediated pyroptosis to improve cognitive function in a rat model of Alzheimer's disease(AD). Methods Rats were randomly divided into the following groups(n=12):Normal group,AD group,TQHXD low-dose group,TQHXD high-dose group,donepezil group,and TQHXD high-dose+Caspase-3 activator(Raptinal)group.Except for the normal group,rats in the other groups received bilateral hippocampal injection of β-amyloid 25-35(Aβ_25-35)to establish the AD model.After successful modeling,treatments were administered once daily for 4 weeks.Cognitive function was assessed using the Morris water maze test;HE staining was used to examine histopathological changes in the hippocampal CA1 region and assess neuropathological scores;the number of Gasdermin E N-terminal fragment(GSDME-N)-positive cells in the hippocampal CA1 region was determined by immunofluorescence staining;levels of interleukin-1β(IL-1β)and IL-18 in the hippocampal CA1 region were measured by ELISA;and the protein levels of cleaved Caspase-3 and GSDME-N in the hippocampal CA1 region were determined by Western blotting. Results Compared with the normal group,the AD group showed disordered neuronal arrangement,nuclear pyknosis,significant inflammatory cell infiltration,increased escape latency,decreased number of platform crossings,and increased neuropathological scores,number of GSDME-N-positive cells,and levels of IL-1β,IL-18,cleaved Caspase-3,and GSDME-N protein in the hippocampal CA1 region(all P<0.05).Compared with the AD group,the TQHXD low-dose group,TQHXD high-dose group,and donepezil group exhibited alleviated pathological damage in the hippocampal CA1 region,decreased escape latency,increased number of platform crossings,and decreased neuropathological scores,number of GSDME-N-positive cells,and levels of IL-1β,IL-18,cleaved Caspase-3,and GSDME-N protein in the hippocampal CA1 region(all P<0.05).Compared with the TQHXD high-dose group,the TQHXD high-dose+Raptinal group showed more severe pathological damage in the hippocampal CA1 region,increased escape latency,decreased number of platform crossings,and increased neuropathological scores,number of GSDME-N-positive cells,and levels of IL-1β,IL-18,cleaved Caspase-3,and GSDME-N protein(all P<0.05). Conclusion TQHXD may inhibit neuronal pyroptosis and neuroinflammation in AD rats by suppressing the Caspase-3/GSDME pathway,thereby improving cognitive function.

Key words: Tongqiao Huoxue decoction, Alzheimer's disease, neuronal pyroptosis, neuroinflammation, cognitive function

CLC Number:

Lei Ting, Cui Yinglin, Cheng Shuaifang et al. Tongqiao Huoxue Decoction Improves Cognitive Function in Alzheimer's Disease Rats byRegulating Caspase-3/GSDME Pathway-Mediated Pyroptosis[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(2): 214-219.

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