外源性硫化氢对老龄脑缺血再灌注损伤的保护作用及机制

Perioperative cerebral ischemia and reperfusion（ischemia/reperfusion, I/R）injury is an important cause of the aging patients mortality and cognitive dysfunction after operation. It's a serious threat to the safety and quality of elder patients' life, and imposes a heavy burden to the society and the family as well. However, the underlying mechamism has not been elucidated. We found that exogenous hydrogen sulfide (H2S) could reduce the injury of cerebral I/R in rats. On the basis of our preliminary studies, the project is to further probe the protective effect, the dose-response relationship and the protection time window of exogenous H2S on the cerebral I/R injury in the aged rats. We plan to explore whether HMGB1 and the HMGB1/RAGE-MAPK pathway were involved in the protective effect of exogenous H2S on the cerebral I/R injury in the aged rats at the same time. Hoping to provide a new strategy in the treatment of perioperative aging cerebral ischemic injury and the neurological dysfunctions for the future clinical practice.

围术期脑缺血再灌注（ischemia/reperfusion, I/R）损伤是老龄患者术后死亡及认知功能障碍的重要原因，严重威胁老龄患者生命安全及生存质量，同时给社会及家庭带来沉重负担。目前其机制尚未阐明。我们发现脑I/R后给予外源性硫化氢（H2S）可减轻成年大鼠脑损伤。本项目拟在前期研究的基础上，进一步确定外源性H2S对老龄大鼠脑I/R损伤的保护作用，摸索其治疗老龄脑I/R损伤的量效关系及保护时间窗。同时探讨炎症反应警报素HMGB1与其介导的HMGB1/RAGE- - MAPK通路在外源性H2S对老龄大鼠脑I/R损伤中的作用。为临床治疗围术期老龄缺血性脑损伤及其所致神经功能障碍提供新策略。

围术期脑缺血再灌注（ischemia/reperfusion, I/R）损伤是患者，尤其老龄患者术后死亡及认知功能障碍的重要原因，严重威胁患者生命安全及生存质量，并给社会及家庭带来沉重负担。我们应用细胞氧糖剥夺（Oxygen-glucose Deprivation, OGD）模型和大鼠局灶性脑缺血（Middle Cerebral Artery Occlusion, MCAO）模型试验发现，外源性H2S有剂量依赖性的神经保护效应。机制研究显示其保护机制与降低丙二醛浓度，增强超氧化物歧化酶、谷胱甘肽过氧化物酶的活性，增加抗氧化能力、恢复线粒体功能以降低活性氧族的水平并抑制凋亡有关。进一步分析显示NaHS能够抑制PARP-1、AIF以及PP2A表达，增强ERK1/2磷酸化以及GAP-43表达，从而改善缺血缺氧后神经元生长发育，起到神经保护作用。为进一步评价外源性H2S减轻脑I/R损伤的可行性及机制研究奠定了基础，也为探讨脑I/R损伤治疗的新方法及机制提供了前提条件。