心理应激对大鼠氧化应激的影响及TLR4的作用

Effect of psychological stress on oxidative stress in rats and the role of TLR4.

目的观察心理应激对大鼠氧化应激和炎症反应的影响,探讨心理应激在动脉粥样硬化病变形成中的作用、机制。方法雄性Wistar大鼠40只,随机分为正常对照组(NC)、无应激组(NS)、生理应激组(PS)和心理应激组(ES),每组各10只,并制作心理应激模型。于末次应激结束后采集血标本,检测血清SOD活力和MDA含量、放免法测定血清TNF-α水平;HE染色观察大鼠主动脉形态学变化;免疫组化法测定主动脉TLR4表达。结果 (1)血清学指标显示ES组大鼠较其他三组出现了明显的氧化应激损伤(血清SOD活力明显下降而MDA含量明显升高,均P<0.05)和炎症反应(血清TNF-α升高,P<0.05);同时HE染色发现ES组大鼠主动脉出现早期动脉粥样硬化性改变;(2)ES组大鼠主动脉TLR4表达较其他三组明显上调(P<0.05)。结论氧化应激有可能在AS形成的早期,通过激活TLR4释放TNF-α等炎性因子促进血管壁的炎症反应,进而导致AS形成。

Objeαive To investigate the role of psychological stress in the formation of atherosclerosis by studying the effeαs of psychological stress on oxidative stress and the inflammatory response in rats. Methods Forty male Wistar rats were equally divided into 4 groups： the normal control group （NC group）, no-stress group （NS group）, physical stress group （PS group） and psychological stress group （ES group）. The rat models with psychologi- cal stress were established. The blood samples were immediately obtained after the last stress for assay of serum SOD aαivity, MDA content and the level of TNF-α by radioimmunoassay kit. HE staining was used to deteα the change of rat aorta, and immunohistochemistry was used to deteα the change of expression of TLR4 in rat aorta. Results The ES group showed significantly more evident oxidative stress （decreased SOD aαivity and increased MDA, P〈0.05） and inflammation （elevated TNF-α, P〈0.05） than the remaining three groups. HE staining showed that the ES group had early atherosclerotic changes. The expression of TLR4 was at a higher level in ES group than other groups （P〈 0.05）. Conclusion Oxidative stress might promote vessel wall inflammation by the release of TNF-α and other proin- flammatory cytokins TLR4 induced in the early stage of the formation of atherosclerosis.