罗格列酮对百草枯致大鼠肺损伤的炎症抑制作用  

Inhibitory Effect of Rosiglitazone on Inflammation in Paraquat-induced Lung Injury in Rats

作　　者：刘振宁[1] 高嵩岚[1] 张红雷[1] 赵敏[1] 

机构地区：[1]中国医科大学附属盛京医院急诊科,沈阳110004

出　　处：《医药导报》2015年第8期993-997,共5页Herald of Medicine

基　　金：国家自然科学基金资助项目(81171793);辽宁省教育厅高等学校科学研究一般项目(L2014300)

摘　　要：目的研究罗格列酮对百草枯致大鼠肺损伤过程中的炎症抑制作用机制。方法将72只SD雄性大鼠随机分成3组,每组24只。模型对照组:腹腔注射百草枯20 mg·kg-1;罗格列酮组:腹腔注射百草枯前1 h,腹腔注射罗格列酮10 mg·kg-1;空白对照组:腹腔注射0.9%氯化钠溶液1 m L。注射百草枯后4,8 h及1,3 d,收集各组大鼠血清和肺组织标本,组织切片苏木精-伊红(HE)染色进行肺损伤评分,采用酶联免疫吸附法(ELISA)检测血清白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量,采用免疫组化方法检测NF-κB蛋白在肺组织的表达,利用Western blot法检测肺组织核因子-κB(NF-κB)和激活蛋白(AP-1)蛋白表达水平。结果模型对照组大鼠血清炎性细胞因子IL-1β和TNF-α含量明显增加。罗格列酮组肺组织损伤程度明显降低,血清IL-1β和TNF-α含量减少,肺组织NF-κB和AP-1蛋白的表达降低。结论罗格列酮可以抑制百草枯中毒大鼠肺组织NF-κB和AP-1蛋白表达,减少IL-1β和TNF-α分泌,对百草枯所致大鼠肺损伤炎症有抑制作用。Objective To study inhibition effect of rosiglitazone on lung injury induced by paraquat. Methods 72 male SD rats were randomly divided into three groups （n = 24 ）： model control group, paraqnat （PQ） was administered intraperitoneally at the dose of 20 mg· kg^-1 ; rosiglitazone group, rosiglitazone （ 10 mg · kg^-1 , ip） was administered 1 h before PQ administration; blank control group, 1 mL 0. 9% sodium chloride solution was administered intraperitoneally. The concentration of TNF-α and IL-1β in serum was measured by ELISA at 4, 8 h and 1, 3 day（s） after PQ exposure.The lung injury scores and nuclear factor - kappa B（NF-KB） positive signal were investigated 3 days after PQ exposure by HE staining and immunohistochemistry, respectively.Protein expression levels of NF-KB and activating protein-1 （AP-1） were also determined by using Western blotting. Results The levels of IL-1β and TNF-α in serum of PQ-treated rats were significantly increased as compared with blank control group.Rosiglitazone pretreatment reduced the degree of lung tissue injury, the levels of IL-1β and TNF-α in serum, and the protien expression levels of NF-KB and AP-1 as compared with the model control group. Conclusion Rosiglitazone can inhibit NF-KB and AP-1 protein expression in lung tissue, reduce the levels of IL-1β and TNF-α in serum after PQ exposure, and exert an inhibition effect on inflammation in PQ-induced lung injury of rats.

关 键 词：罗格列酮 百草枯 损伤 肺 核因子-ΚB 激活蛋白-1 炎症 

分 类 号：R977.15[医药卫生—药品] R563.1[医药卫生—药学]