Effects of meglumine cyclic adenylate pretreatment on acute lung injury induced by lipopolysaccharide in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effects of meglumine cyclic adenylate (MCA) pretreatment on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats.Methods Fifty-four adult male Sprague Dawley rats,aged 2-3 months,weighing 200-250 g,were randomly divided into 3 groups (n =18 each) using a random number tablecontrol group (group C),ALI group and MCA pretreatment group (group MCA).ALI was induced with LPS 10 mg/kg injected via the femoral vein in ALI and MCA groups.In group MCA,MCA 2 mg/kg was injected via the femoral vein at 20 min before LPS injection,while the equal volume of normal saline was given in C and LPS groups.Immediately before LPS injection and at 2 and 4 h after LPS injection,the blood samples were taken from the abdominal aorta for determination of PaO2,PaCO2 and plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10).Six rats were sacrificed at 4 h after LPS injection and pulmonary specimens were obtained for microscopic examination of the pathological changes and for determination of cyclic adenosine monophosphate (cAMP) activity (by ELISA) and NF-κB p65 expression in nucleus (by Western blot).Results Compared with group C,PaO2 and cAMP activity in lung tissues were significantly decreased,and PaCO2,plasma concentrations of IL-10 and TNF-α and NF-κB p65 expression in nucleus in lung tissues were increased in group LPS.Compared with group LPS,PaO2,cAMP activity in lung tissues and plasma concentrations of IL-10 were significantly increased,and PaCO2,plasma concentration of TNF-α and NF-κB p65 expression in nucleus in lung tissues were decreased and the pathologic changes of lungs were attenuated in group MCA.Conclusion MCA pretreatment can attenuate ALI induced by LPS,and the mechanism is related to increased level of cAMP,activated cAMP signaling pathway,inhibited NF-κB activity and reduced inflammatory responses in lung tissues of rats.