1. Tongqiao Yizhi granule 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.
- Author
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Yanjiao LI, Linyao H, Shuangyang LI, Yanqi L, Juan W, Raoqiong W, and Xue B
- Subjects
- Animals, Rats, Male, Rats, Sprague-Dawley, Humans, Signal Transduction drug effects, Pyroptosis drug effects, Hippocampus drug effects, Hippocampus metabolism, Dementia, Vascular drug therapy, Dementia, Vascular metabolism, Dementia, Vascular genetics, Caspase 1 metabolism, Caspase 1 genetics, Drugs, Chinese Herbal administration & dosage, Drugs, Chinese Herbal pharmacology, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, NLR Family, Pyrin Domain-Containing 3 Protein genetics, NF-kappa B metabolism, NF-kappa B genetics
- Abstract
Objective: To explore the mechanism by which Tongqiao Yizhi granule (, 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.- Published
- 2024
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