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丹参酮IIA通过调节小胶质细胞的激活和极化及NF-κB信号通路来保护脑缺血再灌注损伤。

Tanshinone IIA Protects Against Cerebral Ischemia Reperfusion Injury by Regulating Microglial Activation and Polarization NF-κB Pathway.

作者信息

Song Zhibing, Feng Jingjing, Zhang Qian, Deng Shanshan, Yu Dahai, Zhang Yuefan, Li Tiejun

机构信息

Department of Pharmacy, Punan Hospital, Pudong New District, Shanghai, China.

College of Pharmacology, Anhui University of Chinese Medicine, Hefei, China.

出版信息

Front Pharmacol. 2021 Apr 19;12:641848. doi: 10.3389/fphar.2021.641848. eCollection 2021.

Abstract

Tanshinone IIA, a fat-soluble diterpenoid isolated from Salvia miltiorrhiza Bunge, has been shown to attenuate the cerebral ischemic injury. The aim of this study was to examine the effects on neuroprotection and microglia activation of Tanshinone IIA. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). We found that Tanshinone IIA significantly reduced infarction volume, alleviated neuronal injuries, reduced the release of TNF-α, IL-1β, and IL-6, increased SOD activity, and decrease the content of MDA in MCAO rats. Hematoxylin and eosin staining, Nissl staining, TUNEL staining and immunofluorescence staining showed that Tanshinone IIA improved the distribution and morphology of neurons in brain tissues and reduced apoptosis. In addition, Co-immunofluorescence staining of rat brain tissues and the mRNA expression levels of CD11b, CD32, iNOS, and Arg-1, CD206, IL-10 in BV2 cells indicated that Tanshinone IIA can downregulate M1 microglia and upregulate M2 microglia in MCAO rats. Further, BV2 microglial cells were subjected to oxygen-glucose deprivation, the protein expression levels were detected by western blot. Tanshinone IIA inhibited the expression levels of NF-κB signaling pathway related proteins. Taken together, this study suggested that Tanshinone IIA modulated microglial M1/M2 polarization the NF-κB signaling pathway to confer anti-neuroinflammatory effects.

摘要

丹参酮IIA是从丹参中分离出的一种脂溶性二萜类化合物,已被证明可减轻脑缺血损伤。本研究的目的是探讨丹参酮IIA对神经保护和小胶质细胞活化的影响。将雄性Sprague-Dawley大鼠进行大脑中动脉闭塞(MCAO)手术。我们发现,丹参酮IIA可显著减小梗死体积,减轻神经元损伤,减少TNF-α、IL-1β和IL-6的释放,增加超氧化物歧化酶(SOD)活性,并降低MCAO大鼠丙二醛(MDA)含量。苏木精-伊红染色、尼氏染色、TUNEL染色和免疫荧光染色显示,丹参酮IIA改善了脑组织中神经元的分布和形态,并减少了细胞凋亡。此外,大鼠脑组织的共免疫荧光染色以及BV2细胞中CD11b、CD32、诱导型一氧化氮合酶(iNOS)和精氨酸酶-1(Arg-1)、CD206、白细胞介素-10(IL-10)的mRNA表达水平表明,丹参酮IIA可下调MCAO大鼠M1小胶质细胞并上调M2小胶质细胞。进一步地,对BV2小胶质细胞进行氧糖剥夺处理,通过蛋白质免疫印迹法检测蛋白质表达水平。丹参酮IIA抑制了核因子κB(NF-κB)信号通路相关蛋白的表达水平。综上所述,本研究表明丹参酮IIA通过调节小胶质细胞M1/M2极化和NF-κB信号通路发挥抗神经炎症作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d4/8090935/af0968ec5743/fphar-12-641848-g001.jpg

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