PM_(2.5)致大鼠肺氧化应激损伤及硫辛酸保护作用

PM_(2.5) induced lung oxidative stress injury and protective effect of lipoic acid against the injury in rats

目的探讨PM_(2.5)对大鼠肺氧化应激损伤及不同剂量硫辛酸(ALA)的保护作用。方法 SPF级雄性SD大鼠48只随机分为对照组、PM_(2.5)组、低、中、高剂量硫辛酸组。不同剂量硫辛酸预处理大鼠24 h后,气管滴注PM_(2.5)连续3 d,禁食8 h后处死,取肺泡灌洗液及肺组织,试剂盒法检测超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)等指标。结果与对照组比较,PM_(2.5)组大鼠体重增重[(63.5±3.69)g]下降;与PM_(2.5)组比较,高剂量硫辛酸组大鼠体重增重[(93.56±4.31)g]明显增加。与对照组比较,PM_(2.5)组大鼠血清SOD、GSH水平显著降低(P <0.05);与PM_(2.5)组比较,中、高剂量硫辛酸组大鼠血清SOD、GSH-Px、GSH水平升高,差异有统计学意义(P <0.05)。与对照组比较,PM_(2.5)组大鼠肺泡灌洗液中GSH-Px、GSH水平显著降低,MDA含量、GSSG/GSH比值增加(P <0.05);与PM_(2.5)组比较,中、高剂量硫辛酸组大鼠肺泡灌洗液中GSH-Px、GSH升高,GSSG/GSH比值降低(P <0.05)。与对照组比较,PM_(2.5)组大鼠肺组织中SOD、GSH-Px、GSH水平显著降低,MDA含量、GSSG/GSH比值增加(P <0.05);与PM_(2.5)组比较,高剂量硫辛酸组大鼠肺组织中SOD、GSH水平升高,GSSG/GSH比值明显降低(P <0.05)。结论一定剂量PM_(2.5)可导致大鼠肺氧化损伤,硫辛酸对PM_(2.5)导致的肺氧化损伤具有一定程度的保护作用。

Objective To observe lung oxidative stress injury induced by particulate matter≤2.5 μm in aerodynamic diameter(PM2.5)and the effect of different dose alpha lipoic acid(ALA)against the injury in rats.Methods Totally 48 male specific pathogen free Sprague-Dawley rats were randomly assigned into a PM2.5 group with intratracheal instillation of suspension(2 ml/kg)of PM2.5 sampled from ambient air in Weifang city once a day for three days, and three groups of PM2.5 plus low, moderate and high dose ALA(intraperitoneal injection at dosages of 20, 40, 80 μg/kg 24 hours before the PM2.5 treatment), and a control group with intratracheal instillation and intraperitoneal injection of saline. By the end of the treatments, all the rats were sacrificed after 8 hours of fasting;then, bronchoalveolar lavage fluid(BALF)and lung tissue specimens were collected for detections of superoxide dismutase(SOD), glutathione(GSH), glutathione peroxidase(GSH-Px), and malondialdehyde(MDA)using kit assays.Results The body weight gain of PM2.5 group was significantly lower than that of control group(63.5±3.69 g vs. 96.35±4.32 g);while the body weight gain(93.56±4.31 g)of PM2.5 plus high-dose ALA pretreatment group was significantly higher than that of PM2.5 group. Compared to those of the control group, the serum SOD and GSH of PM2.5 group decreased significantly(both P<0.05)and compared to those of the PM2.5 group, the serum SOD, GSH-Px, and GSH of the PM2.5 plus moderate and high ALA pretreatment group increased significantly(P<0.05 for all). The GSH-Px and GSH decreased significantly but the MDA and glutathione disulfide(GSSG)/GSH ratio increased significantly in BALF of the PM2.5 group in comparison to those of the control group(P<0.05 for all);while, the GSH-Px and GSH increased but the GSSG/GSH ratio in BALF of the PM2.5 plus moderate and high ALA pretreatment group decreased significantly in contrast to those of the PM2.5 group(P<0.05 for all). Significantly decreased SOD, GSH-Px, and GSH and increased MDA and GSSG/GSH ratio were observed in lung tissues of the PM2.5 group compared to those of the control group(P<0.05 for all);whereas, the PM2.5 plus high ALA pretreatment group demonstrated significantly increased SOD and GSH and decreased GSSG/GSH ratio compared to the PM2.5 group(P<0.05 for all).Conclusion PM2.5 at certain dosages could induce lung oxidative damage and pretreatment with different dose of alpha lipoic acid is of protective effect against the injury in rats.