摘要
目的研究PPAR-γ受体激活对百草枯中毒致大鼠急性肺损伤的保护作用。方法 48只SD雄性大鼠随机平均分成3组,A组(百草枯中毒组):按照20 mg/kg剂量腹腔注射;B组(低剂量PPAR-γ受体激动剂罗格列酮预处理组):在给予百草枯腹腔注射前1 h腹腔注射3 mg/kg罗格列酮;C组(高剂量PPAR-γ受体激动剂罗格列酮预处理组):在给予百草枯腹腔注射前1 h腹腔注射10 mg/kg罗格列酮;D组(对照组):1 m L生理盐水腹腔注射。在注射百草枯后24 h和72 h时,每组取出6只,收集血清和肺组织标本。采用Elisa方法检测血清中IL-1β和TNF-α含量测定,行组织切片HE染色进行肺损伤评分,利用Western blot方法检测肺组织中caspase-3和AP-1蛋白表达水平,采用免疫组化方法检测caspase-3蛋白在肺组织中的表达。结果大鼠百草枯中毒后血清炎性细胞因子IL-1β和TNF-α含量明显增加。肺湿重/干重比以及肺损伤评分明显增加。罗格列酮预处理组可以减轻肺组织损伤程度,降低血清中IL-1β和TNF-α含量,减少肺组织中caspase-3和AP-1蛋白的表达。结论应用PPAR-γ激动剂罗格列酮可以抑制百草枯中毒大鼠肺组织中caspase-3和AP-1蛋白表达,抑制炎症反应和凋亡,对百草枯中毒导致急性肺损伤产生保护作用。
Objective To study the protective effect of PPAR-γ receptor activation on acute lung injury induced by paraquat poisoning in rats. Methods 48 male Sprague-Daw ley rats were randomly divided into three groups. Group A（ paraquat poisoning）,paraquat was administered intraperitoneally at the dose of 20 mg / kg; Group B（ low dose PPAR-γ agonist rosiglitazone pretreatment）,rosiglitazone（ 3 mg /kg,ip） was administered 1 h before PQ exposure pretreatment group; Group C（ high dose PPAR-γ agonist rosiglitazone pretreatment）,rosiglitazone（ 10 mg / kg,ip） was administered 1 h before PQ exposure pretreatment group; Group D（ control）,1 mL normal saline was administered intraperitoneally. The concentration of TNF-α and IL-1β in venous blood was measured via Elisa at 24 h and 72 h after PQ exposure. The lung injury scores and caspase-3 positive signal were detected and analyzed at 72 h after PQ exposure via HE staining and immunohistochemistry respectively. Caspase-3 and AP-1 protein expression were also determined by using Western blot. Results The levels of IL-1β and TNF-α in the peripheral blood of PQ-treated rats were significantly increased compared with control group. Caspase-3 positive signal were detected in the lung tissues of PQ treated rats. PPAR-γ receptor activation could attenuate lung tissue damage; decrease the caspase-3 and AP-1 protein expression compared with the PQ group. Conclusion PPAR-γ receptor activation can inhibit caspase-3 and AP-1 protein expression in lung tissue,attenuate inflammation and apoptosis,and exert a protective effect against paraquat-induced acute lung injury.
出处
《实用药物与临床》
CAS
2015年第3期249-252,351,共5页
Practical Pharmacy and Clinical Remedies
基金
国家自然科学基金资助项目(81171793/H1503)
卫生部国家临床重点专科建设项目(2012-649)
辽宁省教育厅高等学校科学研究一般项目(L2014300)
