Baicalin Inhibits NLRP3 Inflammasome Activity Via the AMPK Signaling Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury
Baicalin Inhibits NLRP3 Inflammasome Activity Via the AMPK Signaling Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury
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黄芩苷通过 AMPK 信号通路抑制 NLRP3 炎症小体活性，减轻脑缺血再灌注损伤
DOI：
10.1007/s10753-021-01486-z
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发表时间：
2021-06-02
期刊：
影响因子：
5.1
通讯作者：
Cao，Xiao-Lu
中科院分区：
文献类型：
--
作者：
Zheng，Wen-Xia;He，Wen-Qi;Cao，Xiao-Lu
已有报道黄芩苷对神经诱导的缺氧缺血损伤有改善作用，但其在脑缺血再灌注时NLRP3炎症性炎症反应中的作用尚不清楚。为了探讨黄芩苷减轻脑缺血再灌注损伤的分子机制，我们研究了调节NLRP3炎症体活性的AMPK信号通路。SD大鼠大脑中动脉闭塞2 h再灌流24 h后，分别以100 mg/kg和200 mg/kg剂量给予黄芩苷治疗。MCAO/R治疗可明显增加脑梗塞体积，改变神经细胞超微结构，激活NLRP3炎性小体，表现为NLRP3、Asc、裂解半胱氨酸天冬氨酸蛋白酶-1、IL-1β和IL-18的表达显著增加。我们的结果表明，黄芩苷以剂量依赖的方式有效地逆转了这些现象。此外，抑制NLRP3的表达可促进黄芩苷对大脑皮层神经元的保护作用。此外，黄芩苷还能显著增加缺氧缺糖/再灌流(OGD/R)后p-AMPK的表达。当化合物C阻断AMPK通路时，NLRP3炎症体的表达也增加。综上所述，我们的研究结果表明，黄芩苷降低了NLRP3炎症体的活性，从而通过激活AMPK信号通路来抑制脑缺血再灌注损伤。
Baicalin has been reported to have ameliorative effects on nerve-induced hypoxic ischemia injury; however, its role in the NLRP3 inflammasome-dependent inflammatory response during cerebral ischemia-reperfusion remains unclear. To investigate the molecular mechanisms involved in baicalin alleviating cerebral ischemia-reperfusion injury, we investigated the AMPK signaling pathway which regulates NLRP3 inflammasome activity. SD rats were treated with baicalin at doses of 100 mg/kg and 200 mg/kg, respectively, after middle cerebral artery occlusion at 2 h and reperfusion for 24 h (MCAO/R). MCAO/R treatment significantly increased cerebral infarct volume, changed the ultrastructure of nerve cells, and activated the NLRP3 inflammasome, manifesting as significantly increased expression of NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18. Our results demonstrated that baicalin treatment effectively reversed these phenomena in a dose-dependent manner. Additionally, inhibition of NLRP3 expression was found to promote the neuroprotective effects of baicalin on cortical neurons. Furthermore, baicalin remarkably increased the expression of p-AMPK following oxygen glucose deprivation/reperfusion (OGD/R). The expression of the NLRP3 inflammasome was also increased when the AMPK pathway was blocked by compound C. Taken together, our findings reveal that baicalin reduces the activity of the NLRP3 inflammasome and consequently inhibits cerebral ischemia-reperfusion injury through activation of the AMPK signaling pathway.