摘要
目的探讨HMGA2基因缺失对PM2.5暴露致大鼠肺损伤和心功能不全的影响。方法将野生型(WT)大鼠按体重用随机数字表法分为对照组和PM2.5组,每组5只大鼠;将HMGA2^(-/-)大鼠按体重用随机数字表法分为HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组,每组5只大鼠。对照组和HMGA2^(-/-)组大鼠每天气管滴注0.3 ml 0.9%氯化钠溶液,PM2.5组和HMGA2^(-/-)+PM2.5组每天气管滴注0.3 ml PM2.5混悬液,连续4周后对大鼠的心功能[左心室射血分数(LVEF)、左心室缩短分数(LVFS)]和肺功能[肺活量(FVC)、最大通气量(MVV)]进行评价,检测大鼠血清中白介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、3-硝基酪氨酸(3-NT)和4-羟基壬烯醛(4-HNE)水平,同时检测肺和心脏组织中高迁移率族蛋白A2(HMGA2)、核转录因子-κB(NF-κB)和过氧化物还原判酶5(PRDX5)蛋白水平。结果HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组大鼠肺和心脏组织中HMGA2无表达;与对照组比较,PM2.5组肺和心脏组织中HMGA2表达降低,差异有统计学意义(P<0.05);与对照组比较,HMGA2^(-/-)组各指标差异无统计学意义(P>0.05);与对照组比较,PM2.5组和HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB和PRDX5降低(P<0.05);与PM2.5组比较,HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB增加、PRDX5降低(P<0.05)。结论HMGA2基因敲除能加重PM2.5暴露致大鼠肺损伤和心功能不全,其机制可能与炎症和氧化应激有关。
Objective To investigate the effects of HMGA2 gene deletion on the lung injury and cardiac insufficiency in rats induced by PM 2.5 exposure.Methods The wild-type(WT)rats were randomly divided into control group and the PM 2.5 group,with 5 rats in each group.The HMGA2/-rats were randomly divided into HMGA2/group and HMGA2/+PM 2.5 group,with 5 rats in each group.The rats in control group and HMGA2/group were instilled with 0.9%sodium chloride solution,0.3 ml daily through the trachea,for 4 weeks.The heart function and lung function of rats were evaluated,and the serum levels of IL-6,TNF-α,3-NT and 4-HNE were detected,moreover,the levels of HMGA2,NF-κB and PRDX5 protein in lung and heart tissue were detected.Results There was no expression of HMGA2 in lung and heart of rats in HMGA2/group and HMGA2/+PM 2.5 group.Compared with those in control group,the expression levels of HMGA2 in PM 2.5 group were significantly decreased(P<0.05).Compared with those in control group,the related indexes in HMGA2/group had no significant differences(P>0.05).Compared with those in control group,the levels of FVC,MVV,LVEF and LVFS in PM 2.5 group and HMGA2/+PM 2.5 group were decreased,while the levels of IL-6,TNF-α,3-NT and 4-HNE were increased,and the levels of NF-κBand PRDX5 in heart and lung were significantly decreased(P<0.05).Compared with those in PM 2.5 group,the levels of FVC,MVV,LVEF and LVFS in HMGA2/+PM 2.5 group were decreased,however,the levels of IL-6 and TNF-αwere significantly increased(P<0.05),and the NF-κB levels in lung and heart were significantly increased,but,the PRDX5 levels were significantly decreased(P<0.05).Conclusion HMGA2 gene knockout can aggravate the lung injury and cardiac insufficiency in rats induced by PM 2.5 exposure,and its action mechanism may be related to inflammation and oxidative stress.
作者
张钰凡
余宏鑫
唐宋
梁建军
ZHANG Yufan;YU Hongxin;TANG Song(Emergency Department,No.3201 Hospital,Shaanxi,Hanzhong 723000,China;不详)
出处
《河北医药》
CAS
2022年第10期1479-1482,共4页
Hebei Medical Journal
