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

Effects of vitamin E and ω-3 fatty acids on protecting ambient PM_(2.5)-induced cardiovascular injury

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 whether vitamin E（ Ve） and ω-3 polyunsaturated fatty acids（ ω-3 FA） could prevent the fine particulate matter（ PM（2.5））-induced cardiovascular injury and explore the potential mechanism. Methods The SD rats were assigned randomly to 8 groups,those were control group,PM（2.5）group,Ve treatment groups（ 3,10,30 mg/（ kg·d）） and ω-3 FA treatment groups（ 10,30 and 90 mg/（ kg·d））. The rats were pretreated with different concentration of Ve and ω-3 FA separately for 14 days,then were exposed to ambient PM（2.5） by intratracheal instillation（ 10 mg/kg BW）. All the rats were sacrificed after the last PM（2.5） exposure,then the arterial blood,lungs and cardiac tissues were collected. The expressions of tumor necrosis factor-α（ TNF-α）,interleukin-1β（ IL-1β）,interleukin-6（ IL-6） in serum,bronchoalveolar lavage fluid and supernatant of cardiac tissue were detected by ELISA kits. The levels of malondialdehyde（ MDA）,superoxide dismutase（ SOD） and glutathione-peroxidase（ GSH-Px） in serum and myocardium were also measured. Results Compared with the severe injury of rats in PM（2.5） exposure group,the rats in Ve or ω-3 FA groups had a slighter injury in lung and cardiac tissue with the increase of Ve and ω-3 FA. Similarly,the levels of IL-1β,IL-6 in bronchoalveolar lavage fluid had a decreasing trend with the increase of Ve and ω-3 FA compared with the PM（2.5） exposure groups. Meanwhile,the expressions of TNF-α in Ve and ω-3 FA high dose groups were significantly reduced when compared with the PM（2.5） exposure group（ P〈0. 05）. In addition, the MDA levels in serum were markedly decreased and the activities of SOD were significantly increased compared with the PM（2.5）exposure group（ P〈0. 05 or P〈0. 01） whereas the SOD activities were elevated only in the ω-3 FA high dose groups（ P〈0. 05）. Meanwhile,the levels of IL-6 and TNF-α in serum had an obvious decrease compared with the PM（2.5） exposure group（ P〈0. 01）.Similarly,compared with the PM（2.5）exposure group, the expressions of MDA were markedly decreased and the activities of SOD and GSH-Px in myocardium were significantly increased（ P〈0. 05 or P〈0. 01） in the Ve treatment group. In addition,the activities of GSH-Px was found higher only in the ω-3 FA high treatment group compared with the PM（2.5）exposure group（ P〈0. 05）. Meanwhile,the levels of IL-1β and TNF-α in cardiac tissue had an obvious decrease trend with the increase of Ve and ω-3 FA.Conclusion PM（2.5） exposure may increase inflammatory response and oxidative stress,supplementation with Ve and ω-3 FA could prevent the PM（2.5）-induced inflammatory reaction and oxidative stress damage by increasing the activities of SOD and GSH-Px.