Acacetin protects rats from cerebral ischemia-reperfusion injury by regulating TLR4/NLRP3 signaling pathway.
10.19540/j.cnki.cjcmm.20230719.401
- Author:
Lan-Ming LIN
1
;
Zheng-Yu SONG
2
;
Jin HU
2
Author Information
1. Graduate School of Hebei North University Zhangjiakou 075000, China.
2. the First Affiliated Hospital of Hebei North University Zhangjiakou 075000, China.
- Publication Type:Journal Article
- Keywords:
NOD-like receptor protein 3(NLRP3);
Toll-like receptor 4(TLR4);
acacetin;
cerebral ischemia-reperfusion injury;
protective effect
- MeSH:
Rats;
Animals;
NF-kappa B/metabolism*;
bcl-2-Associated X Protein;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*;
Tumor Necrosis Factor-alpha/metabolism*;
Rats, Sprague-Dawley;
Caspase 1/metabolism*;
Toll-Like Receptor 4/metabolism*;
Nimodipine/pharmacology*;
Interleukin-6;
Rats, Wistar;
Signal Transduction;
Infarction, Middle Cerebral Artery;
Reperfusion Injury/prevention & control*;
Superoxide Dismutase/metabolism*
- From:
China Journal of Chinese Materia Medica
2023;48(22):6107-6114
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to investigate the mechanism of acacetin in protecting rats from cerebral ischemia-reperfusion injury via the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. Wistar rats were randomized into sham, model, low-and high-dose acacetin, and nimodipine groups, with 10 rats in each group. The rat model of middle cerebral artery occlusion(MCAO) was established with the improved suture method in other groups except the sham group. The neurological deficit score and cerebral infarction volume of each group were evaluated 24 h after modeling. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), supe-roxide dismutase(SOD), and glutathione(GSH). Western blot was employed to determine the expression levels of B-cell lymphonoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and TLR4/NLRP3 signaling pathway-related proteins(TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β) in the rat brain tissue. Hematoxylin-eosin(HE) staining was employed to reveal the histopathological changes in the ischemic area. Compared with the sham group, the modeling of MCAO increased the neurological deficit score and cerebral infarction volume, elevated the IL-1β, IL-6, TNF-α, and MDA levels and lowered the SOD and GSH levels in the brain tissue(P<0.05). Compared with the MCAO model group, low-and high-dose acacetin and nimodipine decreased the neurological deficit score and cerebral infarction volume, lowered the IL-1β, IL-6, TNF-α, and MDA levels and elevated the SOD and GSH levels in the brain tissue(P<0.05). Compared with the sham group, the model group showed up-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and down-regulated protein level of Bcl-2 in the brain tissue(P<0.05). Compared with the MCAO model group, the acacetin and nimodipine groups showed down-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and up-regulated protein level of Bcl-2 in the brain tissue(P<0.05). In conclusion, acacetin regulates the TLR4/NLRP3 signaling pathway to inhibit neuroinflammatory response and oxidative stress, thus exerting the protective effect on cerebral ischemia-reperfusion injury in rats.
