维生素E和ω-3脂肪酸对大气PM_(2.5)心肺损伤的干预研究

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目的观察维生素E(Ve)和ω-3脂肪酸(ω-3 FA)对大气细颗粒物(PM_(2.5))急性染毒所致心血管损伤的干预效果及可能作用机制。方法将SD大鼠随机分为8组,每组8只,分别为对照组,PM_(2.5)染毒组,Ve干预低、中、高剂量组[3、10和30 mg/(kg·d)],ω-3 FA干预低、中、高剂量组[10、30和90 mg/(kg·d)]。第1~14天,灌胃给予维生素E和ω-3脂肪酸,之后除对照组外其余各组以气管滴注的方式进行PM_(2.5)染毒,染毒剂量为10 mg/kg BW,对照组给予相同剂量的生理盐水。末次染毒后处死小鼠,取动脉血、肺脏和心脏,测量血清、肺灌洗液和心肌组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的含量,以及血清和心肌丙二醛(MDA)的含量,超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性。结果肺脏和心脏病理学评分发现,与PM_(2.5)染毒组相比,随着Ve和ω-3 FA干预浓度的升高,炎症分数逐渐降低(P<0.05或P<0.01)。在肺灌洗液中,在Ve各干预组和ω-3 FA各干预组中,与PM_(2.5)染毒组相比,IL-1β、IL-6的含量随干预剂量的增加而呈一定的下降趋势,在Ve及ω-3 FA干预高剂量组,TNF-α的浓度下降明显(P<0.05)。在血清中,与PM_(2.5)染毒组相比,Ve干预组血清MDA含量明显降低、SOD活力明显升高且差异具有统计学意义(P<0.05或P<0.01)。而在ω-3FA干预组中,与PM_(2.5)染毒组相比,仅ω-3 FA高剂量组SOD活力水平明显升高(P<0.05)。同时,Ve和ω-3 FA的干预均能降低血清中IL-6、TNF-α的浓度(P<0.01)。在心肌组织中,与PM_(2.5)染毒组相比,Ve高剂量组MDA含量明显下降,SOD和GSH-Px活力有所升高(P<0.05或P<0.01)。在ω-3 FA干预组,仅高剂量组的GSH-Px活力显著升高(P<0.05)。随着Ve和ω-3 FA干预剂量的增加,心肌组织中IL-1β、TNF-α的浓度均呈现明显的下降趋势。结论 PM_(2.5)暴露可能会增加心肺组织的炎症反应和氧化应激,而补充Ve和ω-3 FA可以通过提高抗氧化物酶SOD及GSH-Px的活性,从而拮抗PM_(2.5)对机体所造成的心肺系统炎症反应和氧化应激损伤。 Objective To observe the intervention effect of vitamin E (Ve) and ω-3 fatty acids (ω-3 FA) on cardiovascular injury induced by acute exposure to PM 2 (2.5) and its possible mechanism. Methods Sprague - Dawley rats were randomly divided into 8 groups (n = 8, n = 8, control group), PM 2.5 group )] and intervention of omega-3 FA in low, middle and high dose groups [10, 30 and 90 mg / (kg · d)]. From day 1 to day 14, vitamin E and omega-3 fatty acids were administered orally. All the rats except the control group were treated with PM 2.5 by tracheal instillation at the dose of 10 mg / kg BW Groups were given the same dose of saline. The mice were killed after the last exposure, blood samples were taken from the lungs and heart, and the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and leukocyte (IL-6), as well as serum and myocardial malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Results Compared with PM 2.5 group, the inflammation score decreased gradually with the intervention of Ve and omega-3 FA (P <0.05 or P <0.01). In the lung lavage fluid, the levels of IL-1β and IL-6 in the intervention groups of Ve and the intervention group of ω-3 FA were a little higher than those in the PM 2.5 group (P <0.05). The concentrations of TNF-α in the high dose of Ve and omega-3 FA groups decreased significantly (P <0.05). Compared with PM 2.5 group, the level of serum MDA in serum and the activity of SOD in Ve intervention group were significantly lower than those in control group (P <0.05 or P <0.01). However, in the omega-3 FA intervention group, the SOD activity in high-dose omega-3 FA group was significantly higher than that in PM 2.5 group (P <0.05). At the same time, the intervention of Ve and omega-3 FA reduced the concentration of serum IL-6 and TNF-α (P <0.01). In myocardial tissue, compared with PM 2.5 group, the content of MDA in the high dose of Ve significantly decreased and the activity of SOD and GSH-Px increased (P <0.05 or P <0.01). In the omega-3 FA intervention group, GSH-Px activity was significantly increased only in the high-dose group (P <0.05). With the increase of intervention dose of Ve and omega-3 FA, the concentration of IL-1β and TNF-α in myocardium showed a significant decreasing trend. CONCLUSION: PM 2.5 exposure may increase the inflammatory response and oxidative stress in cardiorespiratory and pulmonary tissues, while supplementation of Ve and ω-3 FA can antagonize the effects of PM 2.5 on the body The resulting cardiopulmonary inflammation and oxidative stress damage.
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