Fang Jiang, Zhu Yihao, Wang Handong, Cao Bailu, Fei Maoxing, Niu Wenhao, Zhou Yuan, Wang Xiaoliang, Li Xiang, Zhou Mengliang
Department of Neurosurgery, Jinling Hospital, Nanjing, China.
School of Medicine, Southeast University, Nanjing, China.
Front Neurosci. 2019 Jan 9;12:1006. doi: 10.3389/fnins.2018.01006. eCollection 2018.
Autophagy is associated with secondary injury following traumatic brain injury (TBI) and is expected to be a therapeutic target. Baicalin, a neuroprotective agent, has been proven to exert multi-functional bioactive effects in brain injury diseases. However, it is unknown if Baicalin influences autophagy after TBI. In the present study, we aimed to explore the effects that Baicalin had on TBI in a mice model, focusing on autophagy as a potential mechanism. We found that Baicalin administration significantly improved motor function, reduced cerebral edema, and alleviated disruption of the blood-brain barrier (BBB) after TBI in mice. Besides, TBI-induced apoptosis was reversed by Baicalin evidenced by Nissl staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and the level of cleaved caspase-3. More importantly, Baicalin enhanced autophagy by detecting the autophagy markers (LC3, Beclin 1, and p62) using western blot and LC3 immunofluorescence staining, ameliorating mitochondrial apoptotic pathway evidenced by restoration of the TBI-induced translocation of Bax and cytochrome C. However, simultaneous treatment with 3-MA inhibited Baicalin-induced autophagy and abolished its protective effects on mitochondrial apoptotic pathway. In conclusion, we demonstrated that Baicalin enhanced autophagy, ameliorated mitochondrial apoptosis and protected mice brain in TBI mice model.
自噬与创伤性脑损伤（TBI）后的继发性损伤相关，有望成为一个治疗靶点。黄芩苷作为一种神经保护剂，已被证明在脑损伤疾病中发挥多功能生物活性作用。然而，黄芩苷是否影响TBI后的自噬尚不清楚。在本研究中，我们旨在探讨黄芩苷对小鼠TBI模型的影响，重点关注自噬这一潜在机制。我们发现，给予黄芩苷可显著改善小鼠TBI后的运动功能，减轻脑水肿，并缓解血脑屏障（BBB）的破坏。此外，通过尼氏染色、末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）试验以及裂解的半胱天冬酶-3水平证明，黄芩苷可逆转TBI诱导的细胞凋亡。更重要的是，黄芩苷通过蛋白质免疫印迹法和LC3免疫荧光染色检测自噬标志物（LC3、Beclin 1和p62）来增强自噬，通过恢复TBI诱导的Bax和细胞色素C易位证明改善了线粒体凋亡途径。然而，与3-MA同时处理可抑制黄芩苷诱导的自噬，并消除其对线粒体凋亡途径的保护作用。总之，我们证明黄芩苷可增强自噬，改善线粒体凋亡，并保护TBI小鼠模型中的小鼠大脑。
