阿托伐他汀对哮喘大鼠气道炎症、重塑及血清学相关炎症指标的影响

摘要

目的 探讨阿托伐他汀对卵清白蛋白致敏哮喘模型大鼠气道炎症和重塑的影响.方法 清洁级健康SD雄性大鼠24只按随机数字表法分为对照组、哮喘组和阿托伐他汀组,每组8只.大鼠哮喘模型采用卵清白蛋白致敏和激发,0.9%氯化钠溶液进行致敏和激发的大鼠为对照组,阿托伐他汀组在致敏和激发前以阿托伐他汀灌胃.采用肺功能检测3组大鼠气道呼气阻力;ELISA法测定3组实验动物血清中转化生长因子β1(transforming growth factor-β1,TGF-β1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶9(matrix metallo proteinase-9,MMP-9)及其组织学抑制物1(tissue inhibitor of matrix metalloproteinase-1,TIMP-1)的水平,并计算MMP-9/TIMP-1比值.结果 哮喘组和阿托伐他汀组气道阻力高于对照组,阿托伐他汀组气道阻力低于哮喘组(P<0.05).病理检查显示哮喘组气道炎症明显,阿托伐他汀组与之相比炎症轻微.哮喘组和阿托伐他汀组TGF-β1、VEGF、MMP-9、TIMP-1水平高于对照组,MMP-9/TIMP-1低于对照组,阿托伐他汀组TGF-β1、VEGF、MMP-9、TIMP-1水平低于哮喘组(P<0.05);阿托伐他汀组MMP-9/TIMP-1与哮喘组比较差异无统计学意义(P>0.05).结论 阿托伐他汀能够明显降低哮喘大鼠的气道基本阻力,减轻哮喘大鼠气道炎症.阿托伐他汀治疗能够降低血清中TGF-β1、VEGF、MMP-9及TIMP-1水平,或为其减轻炎症及气道重塑的机制.%Objective To explore the effects of atorvastatin on airway inflammation and remodeling in rats with asthma.Methods SD male rats were used as experimental animals.Twenty-four rats were divided into three groups randomly.The asthma group and atorvastatin group were sensitized and challenged by ovalbumin.Saline were used to be the sensitized and challenged drug in the control group.Airway resistance of the animals was measured by animal lung function meter.The airway inflammation was observed by pathological method.The levels of vascular endothelial growth factor(VEGF), transforming growth factor-β1(TGF-β1), matrix metallo proteinase-9(MMP-9) and tissue inhibitor of matrix metalloproteinase-1(TIMP-1) in serum were measured by ELISA.And the MMP-9/TIMP-1 ratio was also been calculated.Results The airway resistance was higher in asthma group and atorvastatin group than that in normal control group.And the airway resistance was lower in atorvastatin group than that in asthma group(P<0.05).The inflammation observed by pathological method was obvious in asthma model group, and that were slighter in atorvastatin groups when compared with asthma model group.The levels of TGF-β1, VEGF, MMP-9 and TIMP-1 were higher in asthma model group and atorvastatin group than normal control group, and the MMP-9/TIMP-1 ratio in normal control group were lower than asthma group and atorvastatin group.The levels of TGF-β1, VEGF, MMP-9 and TIMP-1 were lower in atorvastatin group compared with asthma model group(P<0.05), but there was no obvious difference in the MMP-9/TIMP-1 ratio between asthma model group and atorvastatin group(P>0.05).Conclusion Atorvastatin improve airway resistance, inflammation and remodeling in rats with asthma.Atorvastatin could decrease the serum levels of VEGF, TGF-β1, MMP-9 and TIMP-1, which may play important roles in prevention of inflammation and remodeling.