Resveratrol Inhibits Oxidative Stress and Regulates M1/M2-Type Polarization of Microglia via Mediation of the Nrf2/Shh Signaling Cascade after OGD/R Injury In Vitro

作者全名："Liu, Jie; Liao, Hongyan; Chen, Yue; Zhu, Huimin; Li, Xuemei; Liu, Jing; Xiang, Qin; Zeng, Fanling; Yang, Qin"

作者地址："[Liu, Jie; Liao, Hongyan; Chen, Yue; Zhu, Huimin; Li, Xuemei; Liu, Jing; Yang, Qin] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China; [Xiang, Qin] Longev Dist Peoples Hosp Chongqing, Dept Neurol, Chongqing 401220, Peoples R China; [Zeng, Fanling] Chongqing Med Univ, Affiliated Hosp 1, Hlth Management Ctr, Chongqing 400016, Peoples R China"

通信作者："Yang, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China.; Zeng, FL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Hlth Management Ctr, Chongqing 400016, Peoples R China."

来源：JOURNAL OF PERSONALIZED MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000901082000001

JCR分区：Q2

影响因子：3.4

年份：2022

卷号：12

期号：12

开始页：　

结束页：　

文献类型：Article

关键词：resveratrol; microglia; polarization; oxidative stress; Nrf2 signaling; Shh signaling; co-culture

摘要："Aims: Microglia are closely related to the occurrence and development of oxidative stress. Cerebral ischemia leads to abnormal activation of microglia. Resveratrol can regulate M1/M2-type microglia polarization, but the underlying mechanism is not well understood, although the Nrf2 and Shh signaling pathways may be involved. Given that resveratrol activates Shh, the present study examined whether this is mediated by Nrf2 signaling. Methods: N9 microglia were pretreated with drugs before oxygen-glucose deprivation/reoxygenation (OGD/R). HT22 neurons were also used for conditional co-culture with microglia. Cell viability was measured by CCK-8 assay. MDA levels and SOD activity in the supernatant were detected by TBA and WST-1, respectively. Immunofluorescence detected Nrf2 and Gli1 nuclear translocation. The levels of CD206, Arg1, iNOS, TNF-alpha, Nrf2, HO-1, NQO1, Shh, Ptc, Smo, Gli1 protein and mRNA were measured by Western blotting or RT-qPCR. Annexin V-FITC Flow Cytometric Analysis detected apoptosis. Results: Resveratrol and Nrf2 activator RTA-408 enhanced the viability of microglia, reduced oxidative stress, promoted M2-type microglia polarization and activated Nrf2 and Shh signaling. ML385, a selective inhibitor of Nrf2, decreased the viability of microglia, aggravated oxidative stress, promoted M1-type microglia polarization and inhibited Nrf2 and Shh signaling. Moreover, resveratrol and RTA-408-treated microglia can reduce the apoptosis and increase the viability of HT22 neurons, while ML385-treated microglia aggravated the apoptosis and weakened the viability of HT22 neurons. Conclusions: These results demonstrated that resveratrol may inhibit oxidative stress, regulate M1/M2-type polarization of microglia and decrease neuronal injury in conditional co-culture of neurons and microglia via the mediation of the Nrf2/Shh signaling cascade after OGD/R injury in vitro."

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