Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway
| Autor: | Niu Xiaoshan, Zhang Yanjun, Yi Zhu, Zhang Xiaoling, Zhang Hui, Bu Juan, Wu Weidong, Zhi Ma, Shi Shen, Zhao Zongfeng, Wang Huiqin |
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| Rok vydání: | 2019 |
| Předmět: |
signaling pathway
0301 basic medicine nerve regeneration acacetin cerebral ischemia-reperfusion injury microglia NLRP3 inflammasome inflammatory factor infarct volume nuclear factor-κB neuroprotection neural regeneration Ischemia Inflammation Pharmacology Neuroprotection lcsh:RC346-429 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Developmental Neuroscience medicine Hippocampus (mythology) lcsh:Neurology. Diseases of the nervous system Acacetin business.industry Cerebral infarction medicine.disease 030104 developmental biology chemistry Tumor necrosis factor alpha medicine.symptom business Reperfusion injury 030217 neurology & neurosurgery Research Article |
| Zdroj: | Neural Regeneration Research, Vol 14, Iss 4, Pp 605-612 (2019) Neural Regeneration Research |
| ISSN: | 1673-5374 |
| Popis: | Acacetin (5,7-dihydroxy-4'-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3 (NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin (acacetin group) or an equal volume of saline (0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1 (Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1β, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1β and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1β, and interleukin-1β were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway. |
| Databáze: | OpenAIRE |
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