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邻苯二甲酸酯(PAEs)是国内外使用量最大的增塑剂,是一类广泛存在的“持久性有机污染物(POPs)”。流行病学研究发现PAEs是一种明确的“儿童持久过敏症(Allergic March)”的环境诱导剂,对PAEs与Allergic March的关系进行分子毒理学研究,有助于揭示PAEs致人体免疫毒性的分子机理。本文拟以“环境相关疾病导向性分子毒理学研究策略”为工具,展开对“氧化应激-TSLP/TRPV1-I型超敏反应分子通路”科学假说进行详细的解说:即PAEs诱发Allergic March的过程分为上、中、下游分子事件。上游事件为PAEs通过氧化应激通路导致ROS水平上升和GSH水平下降;中游事件为(1)ROS水平上升致使TSLP分子通路活化,(2)GSH水平下降致使TRPV1分子通路活化,两条通路的活化均可以导致IL-4和T-IgE水平的上升;下游分子事件为IL-4和T-IgE水平的上升诱导I型超敏反应在不同器官的发生。
Phthalates (PAEs) are the most widely used plasticizers at home and abroad and are a widespread class of “persistent organic pollutants (POPs).” Epidemiological studies have found that PAEs is a clear “environmental inducer of childhood Allergic March”, molecular toxicology studies on the relationship between PAEs and Allergic March will help to reveal the PAH-induced human immunotoxicity The molecular mechanism. This paper intends to “environmental-related disease-oriented molecular toxicology research strategy” as a tool to start on the “oxidative stress-TSLP / TRPV1-type Hypersensitive molecular pathway ” scientific explanation for a detailed explanation: the PAEs Allergic March induced process is divided into upper, middle and lower molecular events. Upstream events led to the increase of ROS levels and GSH levels by PAEs through oxidative stress pathways; the middle-stream events were (1) the ROS level rise leading to the activation of TSLP molecular pathways, (2) the decrease of GSH levels led to the activation of TRPV1 molecular pathway, activation of both pathways Can lead to the increase of IL-4 and T-IgE levels. The downstream molecular events are the increase of IL-4 and T-IgE levels which induce the development of type I hypersensitivity in different organs.