Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University, College of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Department of Plastic surgery, Second Affiliated Hospital, Zhejiang University, College of Medicine, 1511 Jianghong Road, Hangzhou, 310009, Zhejiang, China.
Sci Rep. 2017 Sep 19;7(1):11883. doi: 10.1038/s41598-017-12160-6.
Early brain injury (EBI) is involved in the process of cerebral tissue damage caused by subarachnoid hemorrhage (SAH), and multiple mechanisms, such as apoptosis and inflammation, participate in its development. Mangiferin (MF), a natural C-glucoside xanthone, has been reported to exert beneficial effects against several types of organ injury by influencing various biological progresses. The current study aimed to investigate the potential of MF to protect against EBI following SAH via histological and biological assessments. A rat perforation model of SAH was established, and MF was subsequently administered via intraperitoneal injection at a low and a high dose. High-dose MF significantly lowered the mortality of SAH animals and ameliorated their neurological deficits and brain edema. MF also dose-relatedly attenuated SAH-induced oxidative stress and decreased cortical cell apoptosis by influencing mitochondria-apoptotic proteins. In addition, MF downregulated the activation of the NLRP3 inflammasome and NF-κB as well as the production of inflammatory cytokines, and the expression of Nrf2 and HO-1 was upregulated by MF. The abovementioned findings indicate that MF is neuroprotective against EBI after SAH and Nrf2/HO-1 cascade may play a key role in mediating its effect through regulation of the mitochondrial apoptosis pathway and activation of the NLRP3 inflammasome and NF-κB.
早期脑损伤（EBI）涉及蛛网膜下腔出血（SAH）引起的脑组织损伤过程，多种机制，如细胞凋亡和炎症，参与其发展。芒果苷（MF），一种天然的 C-葡萄糖苷紫檀烷，据报道通过影响各种生物学进展对几种类型的器官损伤具有有益的作用。本研究旨在通过组织学和生物学评估研究 MF 通过腹腔注射低剂量和高剂量保护 SAH 后 EBI 的潜力。建立了大鼠 SAH 穿孔模型，随后通过腹腔注射给予低剂量和高剂量 MF。高剂量 MF 显著降低了 SAH 动物的死亡率，并改善了它们的神经功能缺损和脑水肿。MF 还通过影响线粒体凋亡蛋白，剂量依赖性地减轻了 SAH 诱导的氧化应激和皮质细胞凋亡。此外，MF 下调 NLRP3 炎性小体和 NF-κB 的激活以及炎性细胞因子的产生，MF 上调 Nrf2 和 HO-1 的表达。上述结果表明，MF 对 SAH 后 EBI 具有神经保护作用，Nrf2/HO-1 级联可能通过调节线粒体凋亡途径和 NLRP3 炎性小体和 NF-κB 的激活来介导其作用。
