膳食丙烯酰胺暴露的神经损伤及黑果枸杞多酚对其损伤的保护作用机制

People in Ningxia enjoy fried food, especially the Hui people. The national center for food safety assessment in the fifth national dietary survey also reported the Acrylamide (ACR) high risk exposure results of Ningxia population. ACR exposure has universality. It is one of endogenous pollution in the frying starchy food with certain nerve toxicity. Oxidative stress is one of the important neurotoxicity mechanism for ACR. Nrf2/ARE signaling pathway is one of the most important pathways in the antioxidant response mechanism in vivo, and plays an important role in oxidative stress of nervous system. Therefore, it is important to improve human body antioxidant capacity with natural products to reduce the ACR induced nerve damage. Studies have reported black Chinese wolfberry polyphenols (BWP) have good nerve protective effect. However, until now most of the research mainly focus on isolation and purification of polyphenols from black Chinese wolfberry and its antioxidant activity, fewer researches have researched on neuroprotection. For this purpose, the present research is to study on dietary ACR exposure induced nerve damage with cross-sectional survey; On the basis of previous studies about Chinese wolfberry bioactivities, this study will also clarify BWP protection mechanism of ACR induced nerve damage through Nrf2 / ARE signal pathway regulation in vivo and in vitro. The results will be published in 2-3 papers, and 2 master degree students will participate in the whole research process. This study has important sense for enhancing the added value of black Chinese wolfberry and for the prevention of nerve oxidative stress injury induced by ACR.

宁夏尤其是回族人群喜食油炸食品，且国家食品安全评估中心第五次全国膳食调查公布宁夏人群处于ACR高风险暴露背景。丙烯酰胺(ACR)暴露有“人群普遍性”，是高温油炸淀粉食品内源污染物之一，有一定神经毒性。氧化应激是ACR神经毒性重要损伤机制，Nrf2/ARE通路是体内抗氧化应答机制中最重要通路之一，在神经氧化应激损伤中起着重要作用。因此，利用天然产物提高机体抗氧化能力减轻ACR神经损伤尤为重要。已有研究报道黑果枸杞多酚（BWP）有很好的神经保护作用。然而目前对其研究多集中于多酚分离纯化及抗氧化活性，对其发挥神经保护作用深入研究较少。因此本课题拟立足枸杞优势产业，在前期研究枸杞功效基础上，通过人群横断面调查研究膳食ACR暴露诱导的神经损伤，从动物细胞水平阐明BWP对Nrf2/ARE的调控和对ACR致神经损伤的保护机制。本课题对提高黑果枸杞附加值和ACR致神经损伤的防治有重要意义。

宁夏当地居民喜食油炸食品，且国家食品安全评估中心第五次全国膳食调查公布宁夏人群处于丙烯酰胺(ACR)高风险暴露背景。ACR暴露有“人群普遍性”，是高温油炸淀粉食品内源污染物之一，有一定神经毒性。氧化应激是ACR神经毒性重要损伤机制，Nrf2/ARE通路是体内抗氧化应答机制中最重要通路之一，在神经氧化应激损伤中起着重要作用。因此，利用天然产物提高机体抗氧化能力减轻ACR神经损伤尤为重要。本课题立足宁夏枸杞优势产业，通过人群横断面调查研究了膳食ACR暴露诱导的神经损伤，结果表明随着ACR暴露水平的增加，研究对象异常情绪增多，行为功能检测正常。因此应重视人群膳食ACR暴露水平较高的食品安全问题，增加多酚类物质的摄入以减少ACR对身体带来的负面效应；在细胞水平，黑果枸杞多酚（LRP）干预提高了SH-SY5Y细胞活力，降低了细胞ROS和MDA的水平，升高了SOD和GSH的含量，以及上调了Nrf2通路下游GCLC、GCLM与HO-1的蛋白表达水平，并下调了凋亡通路p-JNK/JNK、p-p38/p38相关蛋白的表达水平。在动物水平，LRP改善了ACR诱导的大鼠的探索和运动障碍，激活了纹状体和黑质中Nrf2途径的蛋白表达，减弱了纹状体的ROS水平，增加了ACR诱导大鼠的GSH和SOD水平，且纹状体和黑质中的TH神经元和多巴胺及其代谢物二羟苯乙酸、高香草酸的含量明显增加。以上结果表明LRP通过激活Nrf2信号通路和抑制凋亡信号通路，在体内体外对ACR诱导的神经毒性发挥保护作用。本课题研究结果表明黑果枸杞将是一种有效的，安全的多酚膳食来源，并阐述了LRP干预减轻ACR诱导的神经损伤及其保护作用机制，这对提高黑果枸杞附加值和ACR致神经损伤的防治有重要意义。