Original articles

Tongqiao Yizhi granule (通窍益智颗粒) repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats

  • Yanjiao LI ,
  • Linyao HAO ,
  • Shuangyang LI ,
  • Yanqi LUO ,
  • Juan WANG ,
  • Raoqiong WANG ,
  • Xue BAI
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  • 1 College of Integrative Medicine, Southwest Medical University, Luzhou 646600, China
    2 Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China
    3 Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, China

Received date: 2023-03-22

  Accepted date: 2023-07-24

  Online published: 2024-05-15

Supported by

Sichuan Provincial Science and Technology Department Applied Basic Research Project: a Dynamic Contrast Enhanced Magnetic Resonance Imaging-based Study on the Effect of Eind Medicine Kaixuan Method on Blood-brain Barrier Function and Prognosis in Patients with Small to Medium Volume Cerebral Hemorrhage(2020YJ0437);Sichuan Provincial Administration of Traditional Chinese Medicine Science and Technology Special: Study on the Mechanism of Shexiang Huayu Xingnao Granules Reducing Nerve Injury in Cerebral Hemorrhage Model Rats by Regulating Microglia Polarization through Peroxisome Proliferator-activated Receptor γ(2021MS506);Luzhou Basic Application Project: the Mechanism of Tongqiao Yizhi Granules in the Treatment of Vascular Dementia by Regulating Gasdermin D-Mediated Pyroptosis(2020-JYJ-57)

Abstract

OBJECTIVE: To explore the mechanism by which Tongqiao Yizhi granule (通窍益智颗粒, TQYZKL) intervenes pyroptosis to treat vascular dementia (VaD) in a rat model.

METHODS: The rat model of VaD was established by two-vessel occlusion (2VO). The rats were randomly divided into Sham group, Model group, Nimodipine group, TQYZKL (6.2 g·kg-1·d-1), TQYZKL (12.4 g·kg-1·d-1), TQYZKL (24.8 g·kg-1·d-1). The Morris water maze (MWM) test was carried out to test the learning and memory function; Hematoxylin-eosin staining and transmission electron microscopy (TEM) to observe the pathological damage in the hippocampus; Tunel fluorescence staining to detect neuronal pyroptosis in the hippocampus. The expression levels of pyroptosis-related proteins, namely Golgi peripheral membrane protein p65 (P65), nucleotide oligomerization domain-like receptors 3 (NLRP3), caspase-1 and Gasdermin D (GSDMD), were detected using Western blotting and reverse transcription polymerase chain reaction. Moreover, the serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were determined through the enzyme-linked immunosorbent assay.

RESULTS: The study revealed that TQYZKL effectively improved the ability of VaD ratsto learn and memorize, relieved the pathological damage in the hippocampus, restored neuronal morphology, and reduced the expression of pyroptosis-related proteins P65, NLRP3, caspase-1, GSDMD-N, IL-18 and IL-1β (P < 0.05).

CONCLUSION: TQYZKL inhibits neuronal pyroptosis in the hippocampus of VaD rats by regulating nuclear factor kappa-B/NLRP3/caspase-1 signaling pathway, thus exerting a therapeutic effect on VaD in the rats.

Cite this article

Yanjiao LI , Linyao HAO , Shuangyang LI , Yanqi LUO , Juan WANG , Raoqiong WANG , Xue BAI . Tongqiao Yizhi granule (通窍益智颗粒) repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats[J]. Journal of Traditional Chinese Medicine, 2024 , 44(4) : 680 -687 . DOI: 10.19852/j.cnki.jtcm.20240515.005

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