Curcumin Protects against Ischemic Stroke by Titrating Microglia/Macrophage Polarization.
Curcumin Protects against Ischemic Stroke by Titrating Microglia/Macrophage Polarization.
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姜黄素通过滴定小胶质细胞/巨噬细胞极化来预防缺血性中风
DOI：
10.3389/fnagi.2017.00233
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发表时间：
2017
影响因子：
4.8
通讯作者：
Hu X
中科院分区：
文献类型：
--
作者：
Liu Z;Ran Y;Huang S;Wen S;Zhang W;Liu X;Ji Z;Geng X;Ji X;Du H;Leak RK;Hu X
中风是最常见的脑血管疾病，也是致残和死亡的主要原因。缺血性卒中约占所有卒中的80%。其余20%的中风是出血性中风。到目前为止，治疗急性缺血性中风的选择非常有限。最近的研究表明，将小胶质细胞表型从促炎的M1表型转变为抗炎和组织修复的M2表型可能是治疗缺血性中风的有效策略。膳食中的植物化学物质姜黄素在实验性中风模型中显示出了良好的前景，但它对中风后小胶质细胞极化和长期恢复的影响尚不清楚。在这里，我们通过使小鼠大脑中动脉远端闭塞(DMCAO)并在缺血后立即和24小时后腹腔注射姜黄素(150 mg/kg)来解决这些缺口。组织学研究显示，姜黄素治疗后可明显减轻dMCAO后3d的脑缺血损伤。在中风后3、5、7和10天，接受姜黄素治疗的小鼠的感觉运动功能(通过粘合剂去除试验和改良的Garcia评分来衡量)更好。RT-PCR检测显示，在dMCAO后3天，姜黄素治疗组小胶质细胞/巨噬细胞M2表型标记物增加，M1标记物减少。免疫荧光染色进一步显示，姜黄素治疗后10d显著增加CD206+Iba1+M2小胶质细胞/巨噬细胞数，减少CD16+Iba1+M1细胞数。体外实验证实，姜黄素能抑制脂多糖和干扰素-γ(干扰素-γ)诱导的M1极化。姜黄素治疗剂量依赖地减少促炎细胞因子的表达，包括肿瘤坏死因子-α、IL-6和IL-12p70，而对小胶质细胞的存活没有任何毒性影响。综上所述，我们证明姜黄素对小胶质细胞的反应有深刻的调节作用，促进M2小胶质细胞极化，抑制小胶质细胞介导的促炎反应。姜黄素后处理可减少缺血性卒中引起的脑损伤并改善功能结果，为姜黄素可能是一种有前途的卒中治疗策略提供了新的证据。
Stroke is the most common type of cerebrovascular disease and is a leading cause of disability and death. Ischemic stroke accounts for approximately 80% of all strokes. The remaining 20% of strokes are hemorrhagic in nature. To date, therapeutic options for acute ischemic stroke are very limited. Recent research suggests that shifting microglial phenotype from the pro-inflammatory M1 state toward the anti-inflammatory and tissue-reparative M2 phenotype may be an effective therapeutic strategy for ischemic stroke. The dietary phytochemical curcumin has shown promise in experimental stroke models, but its effects on microglial polarization and long-term recovery after stroke are unknown. Here we address these gaps by subjecting mice to distal middle cerebral artery occlusion (dMCAO) and administering curcumin intraperitoneally (150 mg/kg) immediately after ischemia and 24 h later. Histological studies revealed that curcumin post-treatment significantly reduced cerebral ischemic damage 3 days after dMCAO. Sensorimotor functions—as measured by the adhesive removal test and modified Garcia scores—were superior in curcumin-treated mice at 3, 5, 7 and 10 days after stroke. RT-PCR measurements revealed an elevation of M2 microglia/macrophage phenotypic markers and a reduction in M1 markers in curcumin-treated brains 3 days after dMCAO. Immunofluorescent staining further showed that curcumin treatment significantly increased the number of CD206+Iba1+ M2 microglia/macrophages and reduced the number of CD16+Iba1+ M1 cells 10 days after stroke. In vitro studies using the BV2 microglial cell line confirmed that curcumin inhibited lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-induced M1 polarization. Curcumin treatment concentration-dependently reduced the expression of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-12p70, in the absence of any toxic effect on microglial cell survival. In conclusion, we demonstrate that curcumin has a profound regulatory effect on microglial responses, promoting M2 microglial polarization and inhibiting microglia-mediated pro-inflammatory responses. Curcumin post-treatment reduces ischemic stroke-induced brain damage and improves functional outcomes, providing new evidence that curcumin might be a promising therapeutic strategy for stroke.
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影响因子：
--
作者：
Panda AK;Chakraborty D;Sarkar I;Khan T;Sa G
通讯作者：
Sa G
影响因子：
0.8
作者：
Altinay, Serdar;Cabalar, Murat;Gulcubuk, Ahmet
通讯作者：
Gulcubuk, Ahmet
影响因子：
1.9
作者：
Liu, Shuang;Cao, Yungang;Han, Zhao
通讯作者：
Han, Zhao
小胶质细胞和巨噬细胞在器官脑切片中由氧葡萄糖剥夺引起的脑损伤后调节细胞死亡。
影响因子：
6.2
作者：
Girard, Sylvie;Brough, David;Lopez-Castejon, Gloria;Giles, James;Rothwell, Nancy J.;Allan, Stuart M.
通讯作者：
Allan, Stuart M.
影响因子：
6.1
作者：
Lee, Jin Hwan;Wei, Zheng Z.;Cao, Wenyuan;Won, Soonmi;Gu, Xiaohuan;Winter, Megan;Dix, Thomas A.;Wei, Ling;Yu, Shan Ping
通讯作者：
Yu, Shan Ping