Background:The diterpenoid cryptotanshinone (CTS) has wide biological functions, including inhibition of tumor growth, inflammation and apoptosis. The present study aimed to explore the possible effect of CTS on cerebral ischemia/reperfusion (I/R) injury and the underlying mechanisms. Methods:MaleC57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO) and murine microglia BV2 cells were challenged by Oxygen/glucose deprivation, to mimic I/R and ischemic/hypoxic and reperfusion (H/R) injury, respectively. CTS was administered 0.5 h (10 mg/kg) after the onset of MCAO or 2 h (20μM) post OGD. Infarct volume and neurological deficit were measured. Immunofluorescence, qPCR, and western blot, were performed to detect the expression of cytokines, apoptotic marker, and M1/M2 phenotype-specific genes. Flow cytometry was applied for M1/M2 subpopulation or Annexin V/PI apoptosis assessment. Results:CTS significantly reduced cerebral infarct volume, neurologic deficit scores, pro-inflammatory cytokine production (IL-6, TNF-α, and IL-1β), apoptotic protein expression (cleaved caspase-3) of mice after tMCAO challenge. Furthermore, CTS attenuated CD16 + M1-type and elevated CD206 + M2-type microglia in vivo or in vitro. Conclusions:We propose that the neuroprotective effect of CTS in the I/R or H/R context are explained modulation of microglial polarization, suggesting therapeutic potential for cerebral ischemic stroke.

中文翻译：

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隐丹参酮可降低脑缺血再灌注损伤引起的神经毒性，包括调节小胶质细胞极化

背景：二萜类隐丹参酮（CTS）具有广泛的生物学功能，包括抑制肿瘤生长、炎症和细胞凋亡。本研究旨在探讨 CTS 对脑缺血/再灌注 (I/R) 损伤的可能影响及其潜在机制。方法：MaleC57BL/6J 小鼠经历短暂的大脑中动脉闭塞 (tMCAO)，小鼠小胶质细胞 BV2 细胞受到氧/葡萄糖剥夺的挑战，分别模拟 I/R 和缺血/缺氧和再灌注 (H/R) 损伤。CTS 在 MCAO 发作后 0.5 小时 (10 mg/kg) 或 OGD 后 2 小时 (20μM) 给药。测量梗塞体积和神经功能缺损。进行免疫荧光、qPCR 和蛋白质印迹以检测细胞因子、凋亡标记和 M1/M2 表型特异性基因的表达。流式细胞术用于 M1/M2 亚群或膜联蛋白 V/PI 细胞凋亡评估。结果：CTS 显着降低了 tMCAO 攻击后小鼠的脑梗死体积、神经功能缺损评分、促炎细胞因子产生（IL-6、TNF-α 和 IL-1β）、凋亡蛋白表达（切割的 caspase-3）。此外，CTS 在体内或体外减弱 CD16 + M1 型和升高 CD206 + M2 型小胶质细胞。结论：我们提出 CTS 在 I/R 或 H/R 环境中的神经保护作用可以解释为对小胶质细胞极化的调节，这表明对脑缺血性卒中具有治疗潜力。tMCAO 攻击后小鼠的凋亡蛋白表达 (cleaved caspase-3)。此外，CTS 在体内或体外减弱 CD16 + M1 型和升高 CD206 + M2 型小胶质细胞。结论：我们提出 CTS 在 I/R 或 H/R 环境中的神经保护作用可以解释为对小胶质细胞极化的调节，这表明对脑缺血性卒中具有治疗潜力。tMCAO 攻击后小鼠的凋亡蛋白表达 (cleaved caspase-3)。此外，CTS 在体内或体外减弱 CD16 + M1 型和升高 CD206 + M2 型小胶质细胞。结论：我们提出 CTS 在 I/R 或 H/R 环境中的神经保护作用可以解释为对小胶质细胞极化的调节，这表明对脑缺血性卒中具有治疗潜力。