全反式维甲酸对大鼠急性肺损伤的治疗作用及肺组织中基质金属蛋白酶-9表达的影响  

Role of all-trans retinoic acid in therapeutics of acute lung injury in rats and expression of matrix metalloproteinase-9 in lung tissue

作　　者：张媛梅[1] 张婷[1] 周向东[1] 

机构地区：[1]重庆医科大学附属第二医院呼吸内科,重庆400010

出　　处：《中国生物制品学杂志》2012年第3期340-344,共5页Chinese Journal of Biologicals

摘　　要：目的探讨全反式维甲酸(All-trans retinoic acid,ATRA)对大鼠急性肺损伤(Acute lung injury,ALI)的治疗作用及肺组织中基质金属蛋白酶-9(Matrix metalloproteinase-9,MMP-9)表达的影响。方法将SD大鼠随机分为生理盐水对照组、ALI组和ATRA干预组,后两组经尾静脉注射5 ml/kg的脂多糖(LPS)复制ALI模型,ALI组在注射LPS前5 d,每天以植物油灌胃1次,0.5 ml/(kg.次),注射LPS后,经腹腔注射植物油,1 ml/kg;ATRA干预组在注射LPS前5 d,每天以含30 mg/kg ATRA的植物油灌胃1次,0.5 ml/(kg.次),注射LPS后,经腹腔注射含5 mg/kg ATRA的植物油,1 ml/kg。对照组在整个实验过程中均注射生理盐水(0.5 ml/kg)。腹腔注射ATRA 8 h后,处死各组大鼠,测定大鼠动脉血氧分压(PaO2)、支气管肺泡灌洗液(Bronchial alveolar lavage fluid,BALF)中蛋白含量、肺组织湿/干比重(W/D),并观察肺组织形态,采用RT-PCR和免疫组化法分别检测肺组织中MMP-9基因mRNA和蛋白的表达。结果与生理盐水对照组相比,ALI组大鼠肺组织炎性细胞明显增多,动脉PaO2明显降低(P<0.05),W/D、BALF中蛋白含量、肺组织中MMP-9基因mRNA及蛋白表达水平均明显升高(P<0.05或P<0.01);与ALI组相比,ATRA干预组大鼠肺组织炎症反应减轻,W/D、BALF中蛋白含量、肺组织中MMP-9基因mRNA及蛋白的表达水平明显下降(P<0.05或P<0.01),其动脉PaO2也明显改善(P<0.05)。结论 ATRA对大鼠ALI具有治疗作用,其机制可能是通过降低MMP-9的表达实现的。Objective To investigate the role of all-trans retinoic acid（ATRA） in therapeutics of acute lung injury（ALI） in rats and expression of matrix metalloproteinase-9（MMP-9） in lung tissue.Methods SD rats were randomly divided into control,ALI and ATRA intervention groups.The rats in ALI group were administered with vegetable oil by gastric lavage at a dosage of 0.5 ml /（kg·d）,once a day for 5 d,then injected i.v.with LPS and i.p.with vegetable oil（1 ml / kg）,while those in ATRA intervention group were administered with vegetable oil containing 30 mg / kg ATRA by gastric lavage at a dosage of 0.5 ml /（kg·d）,once a day for 5 d,then injected i.v.with LPS and i.p.with vegetable oil（1 ml / kg） containing 5 mg / kg ATRA.However,the rats in control group were injected with physiological saline（0.5 ml / kg） during the whole test.The rats in various groups were killed 8 h after injection i.p.with ATRA,and determined for PaO2,the protein content in brochoalveolar lavage fluid（BALF） and the wet / dry（W / D） ratio of lung tissue,observed for morphology of lung tissue,and analyzed for expressions of MMP-9 mRNA and protein in lung tissue by RT-PCR and immunohistochemcial assay.Results Compared with those in control group,the inflammatory cells in lung tissue of rats with ALI increased significantly,while the PaO2 level decreased significantly（P 0.05）,and the W / D ratio,protein content in BALF as well as the expression levels of MMP-9 mRNA and protein in lung tissue increased significantly（P 0.05 or P 0.01）.However,compared with those in ALI group,the inflammatory reaction in lung tissue of rats in ATRA intervention group was relived,while the W / D ratio,protein content in BALF as well as expression levels of MMP-9 mRNA and protein in lung tissue decreased significantly（P 0.05 or P 0.01）,and PaO2 level increased significantly（P 0.05）.Conclusion ATRA showed curative effect on ALI in rats by a possible mechanism of down-regulation of MMP-9 expression.

关 键 词：维甲酸 急性肺损伤 基质金属蛋白酶9 

分 类 号：R563[医药卫生—呼吸系统]