甲基泼尼松龙对急性肺损伤大鼠肺组织氧化应激和金属蛋白酶的调节作用  

The Regulating Effect of Methylprednisolone on Oxidative Stress and Metalloproteinase of Acute Lung Injury in Rats

作　　者：田巍[1] 赵斌[1] Tian Wei;Zhao Bin(Peking University Fourth School of Clinical Medicine,Beijing 100035,China)

机构地区：[1]北京大学第四临床医学院、北京积水潭医院,100035

出　　处：《医学研究杂志》2018年第9期39-43,48,共6页Journal of Medical Research

基　　金：国家重点基础研究发展规划项目(2006CB503807);国家自然科学基金资助项目(30425010,30571971,30630031);国家长江学者奖励计划;北京市自然科学基金资助项目(7072082,7052043)

摘　　要：目的探讨糖皮质激素对急性肺损伤治疗的作用途径和机制。方法雄性SD大鼠42只随机分为3组:空白对照组(n=6)、油酸造模组(n=18)、甲基泼尼松龙组(n=18)。用油酸制备大鼠急性肺损伤模型,并对急性肺损伤大鼠进行糖皮质激素干预实验,以大体标本病理改变、肺湿/干重比(W/D)、光镜下半定量肺损伤评分(IQA)、动脉血氧分压(PaO_2)、血浆及肺组织MDA和SOD为观察检测指标,同时检测其他相关生化指标(如血浆及肺组织TIMP-1和MMP-9),以便对糖皮质激素治疗的过程进行客观评估,进一步探讨糖皮质激素的作用途径和机制,为探讨ALI的药物干预研究提供实验依据。结果 (1)动脉血氧分压(PaO_2):2、6、18h 3个观察点的PaO_2逐渐升高,且差异有统计学意义;(2)肺湿/干重比(W/D):2、6、18h 3个观察点的W/D逐渐降低,且差异有统计学意义;(3)肺损伤评分(IQA):与6h观察点比较,18h观察点的IQA有降低(P> 0. 05),但差异无统计学意义;(4)血浆和肺组织SOD含量变化:2、6、18h 3个观察点的血浆SOD值逐渐升高,且差异有统计学意义; 6、18h的肺组织SOD值均高于2h的观测值,但18h和6h相比没有明显变化;(5)肺组织MDA含量变化:2、6、18h 3个观察点的肺组织MDA逐渐降低,18h和2h相比较降低明显,差异有统计学意义;(6)肺组织MMP-9含量变化:2、6、18h 3个时间点的肺组织MMP-9值随时间有逐渐降低趋势,但无统计学意义。结论甲基泼尼松龙干预治疗对急性肺损伤模型大鼠有明显的疗效,其可能部分通过对急性肺损伤大鼠血浆和肺组织SOD、MDA、MMP-9和TIMP-1的调节,来改善动脉血PaO_2、W/D、IQA,而发挥抗炎、抗渗出作用,从而为临床防治急性肺损伤提供可能的途径和思路。随着治疗时间进程糖皮质激素起到积极的干预作用。甲基泼尼松龙通过调节血浆和肺组织SOD、MDA及MMP-9、TIMP-1活性或含量改善急性肺损伤大鼠肺部病理损伤这一过程也存�Objective To investigate and verify the therapeutic effect of glucocorticoid on acute lung injury. Methods Forty-two male SD rats were randomly divided into three groups： the blank control group （ n =6）, the oleic acid modeling group （ n =18）, and the Methylprednisolone group （ n =18）. To observe the intervention effects of glucocorticoid （represented by methylprednisolone） to acute lung injury （ALI） rats based on ALI model in rats induced by oleic acid, we detected some related indexes, including histomorphology of lung tissue, index of quantitative assessment score under light microscope （IQA）,lung wet/dry weight ratio （W/D）, arterial partial pressure of oxygen （PaO 2）,super oxide dismutase （SOD） and malondialdehyde in plasma and lung tissue, and other biomedical indicators （matrix metalloproteinase-9 and tissue matrix metalloproteinase inhibitor-1 in plasma and lung homogenate） to evaluate the course of glucocorticoid treatment objectively. The treatment outcomes of glucocorticoid to ALI were further discussed, which would provide experimental basis for drug intervention research on ALI. Results ①Arterial partial pressure of oxygen （PaO 2）： PaO 2 significantly increased in 2h, 6h and 18h. ② Lung wet/dry weight ratio（W/D）： W/D decreased significantly in 2h, 6h and 18h. ③Index of quantitative assessment score under light microscope（IQA）： there was no significant difference between the IQA in 6h and 18h（ P 〉0.05）, even though the IQA in 18h was lower than that in 6h. ④SOD level in plasma and lung tissue： SOD level in plasma and lung tissue increased significantly in 2h, 6h and 18h; lung tissue SOD levels in 6h and 18h are higher than that in 2h, while there was no significant change between SOD levels in 18h and 6h. ⑤Lung tissue MDA： MDA in lung tissue decreased gradually in 2h, 6h and 18h. MDA in 18h was significant lower than MDA in 2h. ⑥ Lung tissue MMP-9： MMP-9 level in lung tissue decreased in 2h, 6h, and 18h（ P 〉0.05�

关 键 词：甲基泼尼松龙 急性肺损伤大鼠 超氧化物歧化酶 丙二醛 基质金属蛋白酶明胶酶B 金属蛋白酶组织抑制因子 

分 类 号：R5[医药卫生—内科学]