Genistein Attenuates Acute Cerebral Ischemic Damage by Inhibiting the NLRP3 Inflammasome in Reproductively Senescent Mice
Genistein Attenuates Acute Cerebral Ischemic Damage by Inhibiting the NLRP3 Inflammasome in Reproductively Senescent Mice
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金雀异黄素通过抑制生殖衰老小鼠的 NLRP3 炎症小体减轻急性脑缺血损伤
DOI：
10.3389/fnagi.2020.00153
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发表时间：
2020
影响因子：
4.8
通讯作者：
Yang Qianzi
中科院分区：
文献类型：
--
作者：
Wang Shiquan;Wang Jin;Wei Haidong;Gu Tingting;Wang Jiajia;Wu Zhixin;Yang Qianzi
绝经后妇女脑卒中的发病率高于同龄男性，雌激素水平的高低被认为是造成这种差异的主要原因。然而，雌激素替代疗法用于预防绝经后卒中显示出有争议的结果，并且由于其长期给药后的严重副作用而受到广泛争议。染料木黄酮（Genistein，Gen）是一种副作用小的天然植物雌激素，对脑缺血损伤具有保护作用。然而，Gen是否能有效预防绝经后中风尚未阐明。在目前的研究中，生殖衰老小鼠在短暂脑缺血损伤之前用Gen（10 mg/kg）处理2周。再灌注24 h后评价神经学评分、梗死体积和细胞凋亡。同时检测炎性因子和炎症因子样受体蛋白3（NLRP 3）相关蛋白的水平。结果表明，Gen治疗减少了梗死体积，改善了神经评分，减弱了细胞凋亡，并减少了炎症因子的释放。小胶质细胞中NLRP 3炎性小体相关蛋白的表达被Gen下调。然而，小胶质细胞中NLRP 3的过表达消除了Gen诱导的炎症因子释放抑制，并逆转了Gen的神经保护作用。结果表明，Gen治疗可减轻生殖衰老小鼠脑缺血诱导的急性损伤，其机制可能是通过抑制NLRP 3炎性小体的表达，小胶质细胞，表明Gen可能是治疗绝经后妇女中风的候选药物。
Postmenopausal women have a higher incidence of stroke compared to the age-matched males, and the estrogen was thought to be the main cause of such difference. However, estrogen replacement therapy for the prevention of postmenopausal stroke shows controversial results and is widely disputed because of its serious side effects after chronic administration. Genistein (Gen), a natural phytestrogen with fewer side effects, has a protective effect against cerebral ischemia damage. However, whether Gen could effectively prevent postmenopausal stroke has not been elucidated. In the current study, reproductively senescent mice were treated with Gen (10 mg/kg) for 2 weeks before having transient cerebral ischemia insults. Neurological scores, infarct volumes, and cell apoptosis were evaluated 24 h after reperfusion. The levels of inflammatory factors and nod-like receptor protein 3 (NLRP3) inflammasome-related proteins were also examined. The results showed that Gen treatment reduced infarct volumes, improved neurological scores, attenuated apoptosis, and decreased inflammatory factor release. The expression of NLRP3 inflammasome-related proteins in microglia was downregulated by Gen. However, the overexpression of NLRP3 in microglia abrogated the Gen-induced inhibition of inflammatory factor release and reversed the neuroprotective effect of Gen. Taken together, the results suggest that Gen treatment could attenuate the acute injury induced by cerebral ischemia in reproductively senescent mice via the inhibition of the NLRP3 inflammasome in microglia, indicating that Gen could be a candidate drug for the treatment of stroke in postmenopausal women.