摘要目的 探讨A2B腺苷受体(A2BAR)在6%羟乙基淀粉(HES)130/0.4降低脓毒症大鼠肺毛细血管通透性中的作用.方法雄性SD大鼠50只,体重250～300 g,随机分为5组(n=10):假手术组(S组)、脓毒症组(CLP组)、低剂量HES组(H1组)、中剂量HES组(H2组)和高剂量HES组(H3组).CLP组、H1组、H2组和H3组采用盲肠结扎穿孔术(CLP)制备脓毒症模型,S组仅开腹后缝合.盲肠结扎穿孔术后4 h时,H1组、H2组及H3组分别经2 h输注6%HES 130/0.4 7.5、15.0、30.0 ml/kg,CLP组给予生理盐水30 ml/kg.CLP后6 h时处死动物,取肺组织,测定肺毛细血管通透性、A2BAR表达、环磷酸腺苷(cAMP)、蛋白激酶A(PKA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)的含量.结果与S组比较,其余各组肺毛细血管通透性和A2BAR表达上调,CLP组肺组织cAMP、IL-6和TNF-α含量升高,H1组、H2组和H3组肺组织cAMP、PKA、IL-6、IL-10和TNF-α含量升高(P＜0.05或0.01);与CLP组比较,H1组、H2组和H3组肺毛细血管通透性均降低,A2BAR表达均上调,肺组织cAMP、PKA和IL-10含量升高,而肺组织IL-6和TNF-α含量降低(P＜0.05或0.01);6%HES 130/0.4降低肺毛细血管通透性及上调A2BAR表达的效应呈剂量依赖性(P＜0.05或0.01);6%HES 130/0.4 15.0ml/kg升高肺组织cAMP和PKA含量及抑制炎性反应的效应最明显(P＜0.05或0.01).结论 6%HES 130/0.4可上调脓毒症大鼠肺组织A2BAR表达,从而降低肺毛细血管通透性.

abstractsObjective To investigate the role of A2B adenosine receptor(A2BAR)in 6% HES 130/0.4-induced reduction of pulmonary capillary permeability in a rat model of sepsis.Methods Fifty male SD rats weighing 250-300 g were randomly divided into 5 groups(n = 10 each): group Ⅰ sham operation(group S);group Ⅱ sepsis(group CLP);group Ⅲ ,Ⅳ,Ⅴ low,medium,high dose HES(group H1,2,3).The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg.Left carotid artery and left femoral vein were cannulated for MAP and HR monitoring and fluid and drug administration.Sepsis was induced by cecal ligation and puncture (CLP).6% HES 130/0.4 7.5,15.0 and 30.0 ml/kg were infused iv over 2 h in group H1,2,3 respectively at 4 h after CLP.The animals were sacrificed at 6 h after CLP.The lungs were isolated for determination of pulmonary capillary permeability(by iv Evans blue injection),the expression of A2BAR and the contents of cAMP,protein kinase A(PKA),TNF-α,IL-6 and IL-10 in the lung tissue.Results CLP significantly increased pulmonary capillary permeability,A2BAR expression and cAMP,IL-6 and TNF-α contents in the lung tissue in group Ⅱ as compared with group S.0.6% HES 130/0.4 significantly reduced pulmonary capillary permeability,increased A2BAR expression,cAMP,PKA and IL-10 and decreased IL-6 and TNF-αcontents in the lung tissue in group H1,2,3 as compared with group CLP.6% HES 130/0.4 decreased pulmonary capillary permeability and up-regulated A2BAR expression in a dose-dependent manner.6% HES 130/0.4 15.0 ml/kg was most effective in increasing cAMP and PKA contents in the lung and depressing inflammatory response.Conclusion 6% HES 130/0.4 decreases pulmonary capillary permeability in a rat model of sepsis by up-regulating A2BAR expression in lung tissue.