Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria
Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria
复制标题
DOI：
10.4103/1673-5374.255972
复制
发表时间：
2019-09-01
影响因子：
6.1
通讯作者：
Gu, Zheng-Tao
中科院分区：
文献类型：
--
作者：
Li, Li;Tan, Hong-Ping;Gu, Zheng-Tao
聚胆碱被认为可以保护各种疾病中不同细胞类型的线粒体。线粒体功能障碍是外伤性脑损伤后继发性脑损伤的一个重要因素。为了研究多丹素对颅脑损伤的保护作用，建立了模拟颅脑损伤损伤的大鼠脑损伤模型。大鼠模型腹腔注射聚丁苷（30 mg/kg）或SIRT1激活剂SRT1720 （20 mg/kg，作为聚丁苷的阳性对照）。在创伤性脑损伤后6小时，采用western blot法检测损伤侧大脑皮层SIRT1、内质网应激相关蛋白和p38磷酸化的表达。流式细胞术检测神经元线粒体超氧化物、线粒体膜电位和线粒体通透性。透射电镜观察神经元线粒体超微结构损伤。我们的研究结果表明，经多胆碱处理后，神经元线粒体中活性氧的释放明显减少；线粒体肿胀减轻；线粒体膜电位维持；线粒体通透性过渡孔打开。内质网应激相关蛋白的激活也受到抑制，包括p-PERK、剪接的XBP-1和剪切的ATF6。SIRT1表达和活性升高；P38磷酸化和裂解caspase-9/3活化被抑制。与单纯创伤性脑损伤大鼠相比，治疗后大鼠神经学评分提高，死亡率降低。这些结果表明，多甙对大鼠创伤性脑损伤的影响具有保护作用，并对神经元线粒体具有保护作用。其机制可能与SIRT1表达和活性增加有关，SIRT1抑制p38磷酸化介导的线粒体凋亡途径。
Polydatin is thought to protect mitochondria in different cell types in various diseases. Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury. To investigate the protective effect of polydatin after traumatic brain injury, a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults. Rat models were intra-peritoneally injected with polydatin (30 mg/kg) or the SIRT1 activator SRT1720 (20 mg/kg, as a positive control to polydatin). At 6 hours post-traumatic brain injury insults, western blot assay was used to detect the expression of SIRT1, endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side. Flow cytometry was used to analyze neuronal mitochondrial superoxide, mitochondrial membrane potential and mitochondrial permeability transition pore opened. Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy. Our results showed that after treatment with polydatin, release of reactive oxygen species in neuronal mitochondria was markedly reduced; swelling of mitochondria was alleviated; mitochondrial membrane potential was maintained; mitochondrial permeability transition pore opened. Also endoplasmic reticulum stress related proteins were inhibited, including the activation of p-PERK, spliced XBP-1 and cleaved ATF6. SIRT1 expression and activity were increased; p38 phosphorylation and cleaved caspase-9/3 activation were inhibited. Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury. These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria. The mechanisms may be linked to increased SIRT1 expression and activity, which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway.