氧化应激-炎症-衰老及其与ApoE基因相关性研究进展

Oxi-inflamm-aging and its association with the polymorphism ofApoE genes

终生的抗原/应激原暴露使机体处于慢性氧化应激状态。氧化应激导致生物分子的氧化损伤,引起机体产生内源性的损伤相关的分子模式(damage associated molecular patterns,DAMPs)和细胞因子的释放。损伤相关的分子模式能激活模式识别受体(pattern recognition receptors,PRRs)与非模式识别受体。细胞因子能激活PRRs下游的信号通路。这些受体介导的信号通路的激活,导致细胞因子和趋化因子释放增加,招募和激活更多的炎性细胞,引起机体系统性慢性无菌炎症反应。机体稳态的调节系统,特别是免疫系统细胞更易因氧化应激遭受损伤,导致机体稳态平衡的破坏,因而在炎症衰老中起重要作用。遗传因素是影响氧化应激-炎症-衰老及老年相关疾病的重要因素,涉及氧化应激、炎症的基因可对炎性衰老产生影响。载脂蛋白ApoE基因多态性明显影响ApoE蛋白的结构与功能,使不同ApoE蛋白表现出不同的抗氧化和抗炎作用,从而影响炎性衰老和老年相关疾病的发展和预后。抗炎结合调节ApoE表达是对抗炎性衰老和老年相关疾病有效手段之一。本文结合我们的前期研究,对以上方面的研究进展作一综述。

The lifelong exposure of antigens and stressors results in chronic oxidative stress situation in the organism. The free radicals and reactive oxygen species （ROS） with high reactivity produced by our cells under oxidative stress will cause oxidative damage in biomolecules. The oxidative damage leads to the releases of both damage-associated-molecular patterns （DAMPs） and intracellular cytokines. DAMPs activate pathogen recognition receptors （PRRs） and non-PRRs. Intracellular cytokines activate signalling pathways downstream of PRRs. Activation of these receptors results in the upregulation of cytokines and chemokines, which are released to recruit and activate additional inflammatory cells and cause the systemic and chronic sterile inflammation. The regulatory system, especially immune systems play an important role in homeostasis maintenance in the organism. The cells of immune systems are very vulnerable to oxidative damage. Once the homeostasis is destroyed, an imbalance between inflammatory and anti-inflammatory networks will occur. Genetic factor also is an important factor of oxi-inflamm-aging and age-related diseases. Many genes are involved in oxidative stress, inflammation process, and the genomic variations within most of these genes might produce different effects on oxi-inflamm-aging. The polymorphism of ApoE genes can affect the antioxidant and immunomodulatory/anti-inflammatory properties of the organism. ApoE genotype-phenotype is associated with the progress and prognosis of oxi-inflamm-aging, age-related diseases as well. Anti-inflammation together with regulation of the expression of ApoE might be an efficient method against oxi-inflamm-aging. Based on our previous studies, the progresses in these areas are reviewed.