甘草酸二铵与地塞米松联用对内毒素诱导ALI大鼠肺组织糖皮质激素受体表达的影响  

Effects of combined diammonium glycyrrhizinate and dexamethasone on the expression of glucocorticoid receptor in rat lung with acute lung injury

作　　者：赵春菱[1] 张剑锋[1] 赵晓琴[1] 邝晓聪[1] 李浩[1] 张伟[1] 庞杰龙[1] 

机构地区：[1]广西医科大学第一附属医院西院急诊科,广西南宁530007

出　　处：《中国急救医学》2013年第8期731-734,I0001,共5页Chinese Journal of Critical Care Medicine

基　　金：广西医疗卫生重点科研项目（重2011092）

摘　　要：目的探讨联合应用甘草酸二铵（DG）和地塞米松（DXM）对内毒素（LPS）所致急性肺损伤（Au）大鼠肺组织糖皮质激素受体（GR）及核因子-κB（NF-κB）表达的影响。方法将40只雄性SD大鼠随机分为生理盐水组、ALI组、DG干预组、DXM干预组和联合用药组（DG＋DXM）。除正常对照组外，其余各组均给予LPS5mg／kg尾静脉注射；LPS注射前1h，DG干预组给予DG20mg／kg静脉注射，DXM干预组给予DXM2mg／kg静脉注射，联合用药组同时给予DG20mg／kg和DXM2mg／kg静脉注射。采用逆转录-PCR反应检测肺组织GRmRNA及NF-KBmRNA的表达；ELISA法测定血清TNF-01、IL-10浓度，同时对大鼠肺组织病理、肺湿干比（W／D）及PaO：等指标进行比较分析。结果①Au组GRmRNA表达明显低于生理盐水组（P〈0．01），而DG干预组及联合用药组GRmRNA表达则明显高于Au组（分别P〈0．05，P〈0．01）；DG干预组、DXM干预组及联合用药组NF-κBmRNA表达均明显低于Au组（均P〈0．01）。②ALI组TNF-α明显高于生理盐水组、DG干预组、DXM干预组和联合用药组（均P〈0．01）。ALI组IL-10明显高于生理盐水组（P〈0．01），但低于DG干预组和联合用药组（均P〈0．01）。③Au组大鼠肺组织水肿明显、中性粒细胞部分浸润，而DG干预组、DXM干预组和联合用药组肺部炎症较Au组减轻。结论甘草酸二铵和地塞米松联用可上调大鼠GR及IL-10的表达，抑制NF-κB及TNF-α的过度表达，从而起到减轻ALI的作用。Objective To investigate the effects of a combination of diammonium glycyrrhizinate （DG） and dexamethasone （DXM） on the expressions of glucocorticoid receptor （GR）, nuclear factor kappa B （NF- KB） in acute lung injury （ALI） induced by lipopolysaccharide （LPS）. Methods Forty male Sprague - Dawley rats were randomly divided into five groups （ n = 8 each） ： normal group, ALl group, DG treatment group, DXM treatment group and combined drug group （ DG ＋ DXM）. Rats in the ALI group, DG treatment group, DXM treatment group and combined drug group （ DG ＋ DXM） were administered with LPS （5 mg/kg） through the vein. In DG treatment group, 1 hour before LPS injecting, DG was administered （20 mg/kg） through the vein. In DXM treatment group, DXM was administered （2 mg/kg）, and DG （20 mg/kg） and DXM （2 mg/kg） were administered simultaneously in combined drug group. The animals were sacrificed after injection of LPS for 4 hours, and then the lung wet/dry ratio and Pa02 were calculated. The histopathology of the lung injury was observed by light microscope. The expression of GR mRNA and NF - KB mRNA in the lung tissues were detected by RT -PCR. The concentration of TNF - ct and IL - 10 in serum were observed by ELISA. The data were expressed as mean ＋ SD and analyzed with SPSS 13.0 software, means were compared with analysis of variance and Student - Newman - Keuls were used to compare 2 means. Results ①The expression level of GR mRNA in ALI group was lower than that in saline group （ P 〈 0.01 ） ; but the expression lever of GR mRNA in DG treatment group and combined drug group were significantly higher than that in ALI group （P 〈 0.05 and P 〈 0.01, respectively）. The expression lever of NF - KB mRNA in DG treatment group, DXM treatment group and combined drug group were lower than that in ALl group （P 〈 0.01 ）. ②TNF-α level in ALI group was the highest among the groups and showed significant difference from the other groups （ P 〈 0.01 �

关 键 词：急性肺损伤(ALI) 甘草酸二铵(DG) 地塞米松(DXM) 糖皮质激素受体(GR) 核因子-κB(NF-κB) 

分 类 号：R644[医药卫生—外科学]