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.
出处
《中国生物制品学杂志》
CAS
CSCD
2012年第3期340-344,共5页
Chinese Journal of Biologicals
关键词
维甲酸
急性肺损伤
基质金属蛋白酶9
Retinoic acid
Acute lung injury（ALI）
Matrix metalloproteinase 9
