Omi/HtrA2信号通路介导脓毒症脑病的作用及机制研究

Sepsis associated encephalopathy (SAE) is the most common in the ICU which can increase mortality significantly, SAE pathogenesis is not clear ，there is no effective therapy , the prognosis is poor.The studies have found that oxidative stress injury, mitochondrial dysfunction, apoptosis, blood-brain barrier damage is involved in the pathogenesis of SAE.Omi/HtrA2 is a kind of oligomeric serine protease,It has been confirmed that Omi/HtrA2 signal pathway can regulate apoptosis, and have important biological functions, which participate in a variety of diseases. Omi/HtrA2 specific inhibitor (UCF - 101) has protective effect, and It has been confirmed that UCF-101 can reduce cerebral ischemia reperfusion injury, and improve neurologic function significantly. We hypothesized that Omi/HtrA2 signal pathway is involved in SAE, our preliminary experiment has confirmed it. we are trying to confirm the role of Omi/HtrA2 signaling pathways involved in SAE and its mechanism by vivo and vitro experiments. It help to discover a novel therapeutic target and new drugs for SAE.

脓毒症相关性脑病(SAE)是ICU中最常见的脑病，合并SAE时脓毒症的病死率明显增加，SAE发病机制至今尚不明确，治疗主要针对脓毒症，对SAE尚无有效治疗，预后较差。研究发现氧化应激损伤、线粒体功能障碍、神经细胞凋亡、血脑屏障破坏是参与SAE发病的重要机制。Omi/HtrA2是一种寡聚丝氨酸蛋白酶, 已证实Omi/HtrA2信号通路不仅参与调节细胞凋亡，而且有重要的生物学功能，是参与多种疾病发病并起关键作用的重要信号通路，而Omi/HtrA2的特异性抑制剂(UCF-101)可对多种器官有保护作用，并已证实能减轻脑缺血再灌注损伤，明显改善神经功能。我们推测Omi/HtrA2信号通路是参与SAE发病重要通路，我们的预实验初步证实这一点。本研究拟分别通过体内外实验研究Omi/HtrA2信号通路介导SAE发病的关键作用及其机制。为SAE的治疗发现新的治疗靶点，为研发新的药物治疗提供理论依据。