Pim-2调控mTOR信号在动脉粥样硬化炎症机制中的作用研究

心血管疾病是重大公共卫生问题，其中动脉粥样硬化(AS)性疾病是重中之重。脂质浸润，炎症细胞侵袭是AS的主要机制。研究证实mTOR信号参与了AS的发生发展，我们前期发现Pim-2能抵抗缺氧复氧损伤而保护心肌细胞，ox-LDL处理巨噬细胞时，炎症因子表达升高，Pim-2、mTOR表达上调，基于Pim-2具抗炎作用，因此我们假设Pim-2也能通过抗炎机制来逆转AS的发生发展，mTOR信号可能是其发挥AS抗炎作用的机制。我们将通过建立Apo E基因敲除AS动物模型及巨噬细胞源性泡沫细胞模型，检测AS条件下Pim-2，mTOR及相关炎症因子的表达，并采用免疫组化、过表达及沉默Pim-2基因及抑制或激活mTOR信号的方法来验证这一假说。通过本项目的研究，我们将证实Pim-2通过调控mTOR信号通路减轻炎症反应而逆转AS，为深入了解AS炎症机制及Pim-2作为新型心血管保护因子提供更多的依据。

Nowadays, atherosclerosis(AS) is one of the most frequent cardiovascular disease, which is a major public health problem in the world. Lipid and inflammatory cell infiltration were the accepted mechanism of AS. It was reported that mTOR signal was an important pathway in AS, our previous studies evidenced that Pim-2 as a cardioprotective protein to against hypoxia/ reoxygenation injury. Pim-2 also played a role in inflammation via mTOR pathway. Base on these, we put forward the hypothesis that Pim-2 can also act an anti-inflammatory mechanism to reverse AS development, and the mTOR signal is the specific mechanism. We propose to apply series experiments in vitro and in vivo, such as ApoE-/- AS animal model, macrophage foam cell model, immunohistochemical, Elisa, over-expression Pim-2 and inhibitory mTOR to verify the anti-inflammatory mechanism of Pim-2 in AS. In short, this study will make a useful exploration to verify the theory that Pim-2 has anti-inflammatory effect in AS and Pim-2 was a new cardioprotective protein.