褪黑素对PM 2.5暴露大鼠肺部炎症反应和氧化应激的影响

The Effect of Melatonin on Pulmonary Inflammation and Oxidative Stress of Rats Exposed to PM 2.5

为探讨褪黑素对大气细颗粒物(PM 2.5)暴露大鼠肺部炎症反应和氧化应激的影响及其机制,本实验将48只清洁级SD大鼠随机(随机数字法)分成4组:空白对照组、NS对照组、PM 2.5组及褪黑素(MT)组,通过气管向肺内注入PM 2.5悬液构建大鼠肺组织PM 2.5染毒模型,并通过灌胃MT溶液,采用肺组织HE染色、ELISA法及蛋白印迹等方法分别检测肺组织病理改变、TNF-α、IL-6、IL-1、MPO、SOD及MDA表达以及NF-κBp65蛋白表达。结果显示:(1)与空白对照组及NS对照组比较,PM 2.5组大鼠肺组织出现明显损伤改变,MT组大鼠肺组织损伤较PM 2.5组明显减轻;(2)PM 2.5组大鼠肺组织TNF-α、IL-6、IL-1表达出现明显增加(p<0.05),MT组较PM 2.5组TNF-α、IL-6、IL-1表达明显下降(p<0.05);(3)PM 2.5组大鼠肺组织SOD表达较空白对照组及NS对照组明显下降(p<0.05),而MPO及MDA表达明显增加(p<0.05),而与PM 2.5组比较,MT组大鼠肺组织SOD表达出现增加,MPO及MDA表达下降(p<0.05);(4)PM 2.5组P65蛋白表达出现明显上调(p<0.05),而MT组较PM 2.5组P65蛋白表达出现明显下降(p<0.05)。由此得出结论,PM 2.5能通过介导肺组织炎性反应及氧化应激导致肺组织损伤,且与活化NF-κB相关,褪黑素能显著抑制PM 2.5所致NF-κB活化,减轻炎性反应及氧化应激,改善PM 2.5暴露大鼠肺损伤。

To analyze the effect and mechanism of melatonin on pulmonary inflammation and oxidative stress of rats exposed to airborne fine particulate matter （PM 2.5）. 48 SD rats of clean grade were randomly divided into four groups： blank control group, NS control group, PM 2.5 group and melatonin （MT） group. Lung PM 2.5 toxic model was set up by intratracheal injection of PM 2.5 suspension into lungs, and by filling the stomach with MT solution, pathological changes of lung tissue, TNF-α, IL-6, IL-1, MPO, SOD, expression of MDA and the protein expression of NF-κBp65 were detected by HE staining, ELISA and Western blotting method, respectively. Results showed that （1） compared with the control group and NS control group, lung tissue injury of rats in PM 2.5 group was apparent, and the lung tissue injury in MT group was significantly lighter than that in PM 2.5 group; （2） the expression of TNF-α, IL-6, and IL-1 in lung tissue of rats in PM 2.5 group significantly increased （p〈0.05）, while those data of MT group decreased compared with PM 2.5 group （p〈0.05）; （3） SOD expression in lung tissue of rats in PM 2.5 group significantly decreased compared with the control group and NS group （p〈0.05）, but the expression of MDA and MPO significantly increased （p〈0.05）, and the SOD expression of lung tissue of rats in MT group appeared to increase, but MPO and MDA expression decreased （p〈0.05） compared with PM 2.5 group; （4） protein expression of P65 in PM 2.5 group obviously up-regulated （p 〈0.05）, while that in the MT group decreased significantly （p 〈0.05）. PM 2.5 could cause lung tissue injury through pulmonary inflammation and oxidative stress and it was associated with the activation of NF-κB. Melatonin could significantly inhibite the activation of NF-κB induced by PM 2.5 to reduce inflammation and oxidative stress and improve lung injury in rats exposed to PM 2.5.