Objective To investigate the effect of diammonium glycyrrhizinate (DG) on the expressions of glucocorticoid receptor and cytokines in serum,and to explore the protective mechanism of DG in acute lung injury (ALI) induced by hemorrhagic shock combined with lipopolysaccharide (LPS). Methods Thirty-six male Sprague-Dawley rats were randomly divided into six groups (n = 6) :sham group, ALI group,DG treated group,dexamethasone treated group, ALI receptor blocked group,and DG treated and ALI receptor blocked group. Rats were administered with LPS (2 mg/kg) after hemorrhagic shock. 1 hour before LPS injection,DG (20 mg/kg) or dexamethasone (2 mg/kg) was administered,and rats in receptor blocked group were administered RU486 (20 mg/ kg). The rat lung wet/dry ratio and PaO2 were calculated, the expression of GR mRNA and GR protein were determined by RT-PCR and Western blot,respectively. The concentration of TNF-α and IL-10 in serum were observed by ELISA. Results (1) TNF-α levels in sham group, ALI group,and DG treated group were (43. 89 ± 7. 25) , (153. 76 ± 20. 69) , and (87. 35 ± 7. 57) ng/L, respectively, and IL-10 levels were (24. 57 ± 8. 41) , (42. 54 ± 6. 58), and (58. 03 ± 9. 66) ng/L, respectively, the difference being significant between groups (F=106. 51,33. 40, all P<0. 01). (2) GR mRNA expression (A) in sham group, ALI group, and DG treated group were (0. 443 ± 0. 017) , (0. 175 ± 0. 026) , and (0. 316 ± 0. 029) , respectively, and GR protein expression were (56. 7 ± 6. 5), (14. 5 ± 2. 6) , and (24. 7 ± 4. 9) , respectively, the difference being significant between groups (F = 86. 068,249. 7, all P< 0. 01). (3) Compared with sham group, infiltration of PMNs, capillary congestion and swelling were found in rat lung of ALI group,treatment with DG could relieve lung injury. Conclusion Diammonium glycyrrhizinate has a protective effect on rats with ALI induced by hemorrhagic shock combined with LPS. It may involve in down-regulating of the expression of TNF-α,and up-regulating of the expression of GR and IL-10.%目的 观察甘草酸二铵(DG)对急性肺损伤(ALI)大鼠肺组织糖皮质激素受体(GR)及血清肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)表达的影响.方法 将36只雄性SD大鼠随机分为假手术组(S组)、ALI组、DG干预组(HLG组)、地塞米松干预组(HLD组)、ALI受体阻断组(ALIR组)和DG干预受体阻断组(HLGR组).各组动物造成失血性休克,然后给予内毒素(LPS)2 mg/kg腹腔注射;LPS注射前1 h,分别给予DG 20 mg/kg或地塞米松2 mg/kg腹腔注射,ALIR组和HLGR组大鼠肌肉注射受体阻断剂RU486.测定大鼠肺湿干比(W/D)、血氧分压(PaO2),并检测肺组织GR mRNA及GR蛋白的表达,同时测定血清TNF-α、IL-10浓度.结果 (1)ALI组TNF-α明显高于S组、HLGR组和HLG组(P<0.01);ALI组IL-10明显高于S组(P<0.01),但低于HLG组和HLGR组(P<0.05).(2)ALI组GR mRNA和蛋白的表达明显低于S组(P<0.01);HLG组GR mRNA和蛋白的表达则明显高于ALI组(P<0.05,P<0.01).(3)ALI组肺组织出现充血、水肿、中性粒细胞浸润,HLG组肺部炎症较ALI组减轻.结论 DG可能通过上调GR及IL-10的表达,同时抑制TNF-α的过度表达,从而起到减轻ALI的作用.
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