氧化应激引发视网膜色素上皮细胞(RPE)炎症反应是视觉功能损伤主要因素之一，抗氧化剂抑制高脂环境诱导RPE氧化应激及炎症反应的机制鲜有报道。课题组前期研究发现原花青素B2抑制脂质沉积诱导RPE氧化损伤，上调未折叠蛋白反应(UPR)关键分子伴侣表达，提示原花青素B2对RPE氧化应激的抑制作用与UPR相关。以此为基础，课题组拟在高脂环境细胞模型和动物模型中，采用特异性抑制剂和基因沉默技术，研究UPR在原花青素B2抑制氧化应激引发RPE细胞炎症反应中的作用；研究原花青素B2对UPR通路关键调控分子XBP1-s的影响，探讨原花青素B2通过XBP1-s对UPR的调控作用以及对UPR下游炎症通路的影响，阐明原花青素B2通过XBP1-s调节UPR通路，从而抑制RPE炎症反应的分子机制。课题完成将为原花青素抑制高脂环境诱导RPE氧化应激提供理论依据，为通过膳食营养缓解脂代谢紊乱相关视觉功能损伤提供新思路。

Dietary supplements have been regarded as efficient strategy to protect retinal pigment epithelium(RPE) from high fat environment induced oxidative stress and inflammation. However, the mechanisms have not been elucidated. Our previous research revealed that procyanidin B2 attenuates lipidosis induced oxidative stress, and inhibits apoptosis in RPE. In addition, Procyanidin B2 upregulates unfolded protein response (UPR) molecular chaperone. These informations indicate that the inhibition on oxidative stress and inflammation by Procyanidin B2 is associated to UPR. Therefore, we’ll investigate the role of UPR in the inhibition on RPE oxidative stress and inflammation by Procyanidin B2 using in vitro and in vivo high fat environment model. The effect of Procyanidin B2 on XBP-1s, the key regulator of UPR, will be studied. Then the regulation of UPR by Procyanidin B2 will be investigated using XBP-1s overexpression and knockdown technology. Lastly, the effect of Procyanidin B2 on inflammation pathway down stream of UPR will be analyzed. The mechanism by which Procyanidin B2 regulates UPR via XBP-1s to inhibit RPE inflammation will be explored. Our research will help to reveal the inhibiting mechanism of high fat environment induced RPE oxidative stress and inflammation by Procyanidin B2, and show new idea of preventing dyslipidemia induced visual impairment.