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| 1 | SIRT1 plays a neuroprotective role in traumatic brain injury in rats via inhibiting the p38 MAPK pathway显示文摘创伤的大脑损害(TBI ) 在经历创伤的损害的病人是残疾和死亡的一个主要原因。Mitochondrial 机能障碍是处于联系 TBI 的大脑损坏贡献第二等的损害的主要因素之一。在 TBI 以后的损害 mitochondrial 功能的证据是,但是位于 TBI 的致病下面的分子的机制不是理解的井。沉默信息管理者家庭蛋白质 1 (SIRT1 ) , NAD +-dependent 蛋白质 deacetylases 的一个成员,被显示了在各种各样的病理的动物模型展出 neuroprotective 活动包括 ischemic 大脑损害, subarachnoid 出血和几 neurodegenerative 疾病。在这研究,我们调查了是否 SIRT1 也施加 neuroprotective 效果 post-TBI,并且推进探索了涉及 TBI 的可能的规章的机制致病。一个侧面的液体敲打(LFP ) 大脑损害模型在老鼠被建立模仿 TBI 的侮辱。SIRT1, p-p38,劈开的 caspase-9 和劈开的 caspase-3 的表示层次都显著地在 12 h post-TBI 被增加并且到达最大值。另外, mitochondrial 功能被损害,由肿、不规则地塑造的线粒体的存在证实了与破坏了并且糟糕定义 cristae, neuronal ATP 内容的有低 m 的神经原的百分比的相对增加, mPTP 的开始,和减少,特别在 12 h post-TBI。有 SIRT1 禁止者 sirtinol 的预告的处理(10 mg/kg, ip ) 导致了 p-p38 激活,加重了 mitochondrial 损坏,并且支持了 mitochondrial apoptosis 小径的激活。相反,有 p38 禁止者 SB203580 的预告的处理(200 g/kg, ip ) 两个的显著地稀释的 post-TBI-induced 表示劈开 caspase-9 并且劈开 caspase-3 和 mitochondrial 损坏,而它没在 SIRT1 上有效果表示。一起,这些结果表明在 TBI 以后的 12 h 可以是第二等的损坏在发生的一关键时间;SIRT1 表示的激活和 p38 MAPK 小径的抑制可以在阻止第二等的损坏 post-TBI 起一个 neuroprotective 作用。为这个原因, SIRT1 和 p38 是可能的是重要目标阻止第二等的损坏 post-TBI。 | Hong YANG Zheng-tao GU Li LI Mac MAEGELE Bi-ying ZHOU Feng LI Ming ZHAO Ke-sen ZHAO | 2017 | Acta Pharmacologica Sinica2017，38，2： | 13 |
| 2 | Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria显示文摘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 intraperitoneally 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.This study was approved by the Animal Care and Use Committee of the Southern Medical University,China(approval number:L2016113)on January 1,2016. | Li Li Hong-Ping Tan Cheng-Yong Liu Lin-Tao Yu Da-Nian Wei Zi-Chen Zhang Kui Lu Ke-Sen Zhao Marc Maegele Dao-Zhang Cai Zheng-Tao Gu | 2019 | Neural Regeneration Research2019，14，9： | 12 |
| 3 | Updated concepts on the pathophysiology and the clinical management of trauma hemorrhage and coagulopathy显示文摘 | Marc Maegele Zheng-Tao Gu Qiao-Bing Huang Hong Yang | 2017 | Chinese Journal of Traumatology2017，20，3： | 7 |
| 4 | Prehospital care for multiple trauma patients in Germany显示文摘 | Marc Maegele | 2015 | Chinese Journal of Traumatology2015，18，3： | 6 |
| 5 | Acute traumatic coagulopathy:Incidence, risk stratification and therapeutic options显示文摘 | Marc Maegele | 2010 | World Journal of Emergency Medicine2010，1，1： | 3 |
| 6 | Plexiform vasculopathy of severe pulmonary arterial hypertension and microRNA expression显示文摘 | Bockmeyer CL Maegel L Janciauskiene S | 2012 | J Heart Lung Transplant2012，31，7： | 1 |
| 7 | The acute coagulopathy of trauma: mechanisms and tools for risk stratification显示文摘 | Maegele M Spinella PCiSchochH | 2012 | Shock2012，38，5： | 1 |
| 8 | Characterization of a new rat model of experimental combined neurotrauma 显示文摘 | Maegele M Riess P Hess S | 2005 | Shock2005，23，5： | 1 |
| 9 | Early rehabilitation model shows positive effects on neural degeneration and recovery from neuromo- tor deficits following traumatic brain injury显示文摘 | Lippert-Gruner M Maegele M Pokorny J et ol | 2007 | Physiol Res2007，56，3： | 1 |
| 10 | Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients显示文摘 | Maegele M Lefering R Yucel N | 2007 | Injury2007，38，3： | 1 |
| 11 | Trauma - associated hyperfibrinolysis显示文摘 | SCHOCHL H VOELCKEL W MAEGELE M | 2012 | Hamostaseologie2012，32，1： | 1 |
| 12 | High plasma to red blood cell ratios are associated with lower mortality rates in patients receiving multiple transfusion(4≤red blood cell units<10)during acute trauma resuscitation显示文摘 | Wafaisade A Maegele M Lefering R | 2011 | J Trauma2011，70，1： | 1 |
| 13 | Ooagulopathy after traumatic brain injury:incidence,pathogenes is, and treatment options显示文摘 | Maegele M | 2013 | Transfusfon2013，53，1： | 1 |
| 14 | Early cogulopathy in multiple iniury: an analysis from the German Trauma Registry on 872 patients显示文摘 | Maegele M Lefering R Yucel N | 2007 | Injury2007，38，29： | 1 |
| 15 | Early coagulopathy inmultiple injury:an analysis from the German Trauma Regis-try on 8724 patients显示文摘 | Maegele M Lefering R Yucel N | 2007 | Injury2007，38，3： | 1 |
| 16 | Epidemiology and risk factors of sepsis after multiple trauma: An analysis of 29,829 patients from the Trauma Registry of the German Society for Trauma Surgery显示文摘 | Arasch Wafaisade Rolf Lefering Bertil Bouillon Samir G. Sakka Oliver C. Thamm Thomas Paffrath Edmund Neugebauer Marc Maegele | 2011 | Critical Care Medicine2011，，4： | 1 |
| 17 | Recruitment of spinal motor pools during voluntary movements versus stepping after human spinal cord injury显示文摘 | Maegele M Muller S Wering A | 2002 | J Neurotrauma2002，19，10： | 1 |
| 18 | Characterization of a new rat model of experimental combined neurotrauma显示文摘 | Maegele M Riess P Sauerland S | 2005 | Shock2005，23，5： | 1 |
| 19 | Functional treatment and early weighthearing after an ankle fracture : a prospective study 显示文摘 | Simanski C J Maegele MG Lefering R | 2006 | J Orthop Trauma2006，20，2： | 1 |
| 20 | Coagulopathy after traumatic brain injury :incidence, patho- genesis, and treatment options显示文摘 | Maegele M | 2013 | Transfusion2013，531，： | 1 |
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