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研究

目的：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。方法将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(melatonin,MT)组,每组各12只。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,并通过灌胃溶液,采用肺组织 HE 染色、酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)及蛋白印迹等方法分别检测肺组织病理改变,如 TNF-α、IL-6、IL-1、MPO、SOD、MDA 以及 NF-κB p65蛋白表达。结果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；②PM 2.5组大鼠肺组织 TNF-α、IL-6、IL-1表达明显增加(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)；③PM 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 表达增加,MPO 及 MDA 表达下降(P <0.05)；④PM 2.5组 p65蛋白表达明显上调(P <0.05),而MT 组较 PM 2.5组 p65蛋白表达明显下降(P <0.05)。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,MT 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。

Melatonin on atmospheric fine particulate matter (PM 2.5) exposed rat lung inflammation and oxidative stress effects and its mechanism

Objective Evaluate the role of melatonin on atmospheric fine particulate matter (PM2.5) exposed rat pulmonary inflammatory response and the influence of oxidative stress and its mechanism.Methods 48 SD rats clean level only stochastic(random number method)is divided into four groups:blank control group,NS control group,PM 2.5 group and melatonin(MT)group,each group 12, injections into the lungs through the trachea PM 2.5 suspension PM 2.5 infected lung tissue of rats model was constructed,and through lavage solution,using HE staining and lung tissue enzyme linked immunosorbent assay(ELISA) method and protein imprinting method respectively to detect changes in lung tissue pathology,TNF-α,IL-6,IL-1,MPO,SOD,MDA and the NF-κB p65 protein expression. Results ①Compared with blank control group and NS control group,a significant lung tissue injury in rats PM 2.5 group change,MT group rats lung tissue injury was significantly reduce PM 2.5 group;②PM 2.5 group of rat lung tissue TNF-α,IL-6,IL-1 expression appears significantly increased (P <0.05),MT group more PM 2.5 group TNF-α,IL-6,IL-1 expression decreased obviously (P < 0.05);③PM 2.5 group of rat lung tissue SOD expression compared with blank control group and NS control group significantly decreased (P < 0.05),while MPO and MDA increased significantly (P < 0.05), while compared with PM 2.5 group,MT group of rat lung tissue SOD expression appears to increase, MPO and MDA decreased(P <0.05);④p65 protein expression in PM 2.5 group was obviously raised( P <0.05),while MT group more PM 2.5 group p65 protein expression decreased obviously(P <0.05). Conclusions PM 2.5 can pass mediated inflammatory reaction of lung tissue and oxidative stress leads to lung tissue damage,and related to the activation of the NF-κB,MT can significantly inhibit PM 2.5 caused by the NF-κB activation,reducing inflammatory reaction and oxidative stress,improve PM 2.5 exposure of lung injury in rats.