HO-1介导烧伤后急性肾损伤内源性保护机制的研究

烧伤后急性肾损伤（AKI）是重度烧伤患者常见并发症，处理不当会严重影响预后。研究表明机体存在对烧伤后AKI的内源性保护机制，但机制尚未明确。我们近期研究利用分子氢及虾青素干预烧伤后肾组织中氧化应激、炎症反应及线粒体相关凋亡，可有效缓解烧伤后肾组织结构破坏及功能减退；且肾组织内HO-1的分布表达随时间明显上调，并伴随部分炎症、凋亡调节蛋白（HMGB-1、NF-κB p65等）表达降低；而药物有效缓解烧伤后急性肾损伤的过程中伴随HO-1的分布表达进一步上调。结合已知HO-1的肾保护作用，我们推测HO-1可能是烧伤后急性肾损伤内源性保护作用的关键蛋白，其具体作用机制亟待阐明。本项目拟利用蛋白芯片、shRNA、基因敲除等方法深入研究HO-1在烧伤后肾组织中的分布表达规律、作用机制及上游调控信号通路，以明确HO-1在内源性保护中的具体作用及分子机制，为烧伤后AKI的的诊治提供新的理论依据。

Acute kidney injury (AKI) is a common and devastating complication in severely burned patients, which may lead to a poor prognosis without appropriate treatments. The previous studies indicate there is an inner defense system against the development of AKI post burn, however, it is unclear about the detailed mechanism and targets of regulation. In our recent study, we found both molecular hydrogen and astaxanthin could protect against the progressive renal dysfunction and histological injury in severely burned rats by ameliorating oxidative stress, inflammation and mitochondria-related apoptosis in renal tissue. In addition, there was a time-relative up-regulation of HO-1 paralleling to the development of AKI post burn, while a down-regulation of downstream HMGB-1or NF-κB p65 (as inflammation or apoptosis relative signals) expression was also observed. Furthermore, we observed an increased distribution and expression of HO-1 secondary to protectants application, combined with a relief of AKI post burn. Therefore, considering the reported nephroprotective effect of HO-1 in diverse kidney injuries or diseases, we infer the key role of HO-1 in the inner protection against AKI after burn insult, and its mechanism of action is still not understood. In the present research project, we intend to explore details of HO-1 about distribution, protein-expression, mechanism of action and upstream regulatory signaling pathway, utilizing protein chip, shRNA, knockout animals and other methods. Finally, we would like to make clear and demonstrate the role and regulatory mechanism of HO-1 in inner protection, which may provide a novel theoretical basis for the diagnosis and treatment of burn induced AKI.