【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（ALI）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LPS 5 mg/kg尾静脉注射;LPS注射前1 h,DG干预组给予DG 20 mg/kg静脉注射,DXM干预组给予DXM 2 mg/kg静脉注射,联合用药组同时给予DG20 mg/kg和DXM 2 mg/kg静脉注射。采用逆转录-PCR反应检测肺组织GR mRNA及NF-κB mRNA的表达;ELISA法测定血清TNF-α、IL-10浓度,同时对大鼠肺组织病理、肺湿干比（W/D）及PaO₂等指标进行比较分析。结果 ①ALI组GR mRNA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GR mRNA表达则明显高于ALI组（分别P<0.05,P<0.01）;DG干预组、DXM干预组及联合用药组NF-κB mRNA表达均明显低于ALI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干预组和合用药组（均P<0.01）。③ALI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ALI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。更多还原

【Abstract】 Objective To investigate the effects of a combination of diammonium glyeyrrhizinate(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,ALI 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 raRNA in the lung tissues were detected by RTPCR.The concentration of TNF-α 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-κB mRNA in DG treatment group,DXM treatment group and combined drug group were lower than that in ALI 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);IL-10 level in ALI group was significantly higher than that in saline group,but lower than that in DG treatment group and combined drug group(P < 0.01).③Compared with normal group,infiltration of PMNs,capillary congestion and swelling were found in ALI group,treatment with DG,or DXM,or combination of DG and DXM could relieve lung injury.Conclusion Combination of diammonium glycyrrhizinate and dexamethasone can alleviate ALI induced by LPS maybe through down-regulating of the expression of NF-κB and TNF-α,and up-regulating of the expression of GR and IL-10.更多还原