ATRA对急性肺损伤大鼠肺组织MMP-9表达的影响

发布时间：2018-05-17 02:04

本文选题：全反式维甲酸 + 急性肺损伤　；参考：《重庆医科大学》2012年硕士论文

【摘要】：目的研究脂多糖（Lipopolysaccharide，LPS）所致急性肺损伤大鼠中基质金属蛋白酶-9（Matrix metalloproteinase-9，MMP-9）及相关炎性指标的变化情况，以及全反式维甲酸（All-trans retinonic acid，ARTA）对其表达的影响，旨在探讨全反式维甲酸在减轻急性肺损伤肺部炎症的治疗作用。方法将30只SD大鼠随机分为3组：生理盐水对照组、ALI组及ATRA干预组。后两组复制急性肺损伤模型通过尾静脉注射脂多糖(5ml/kg)建立，ALI组在尾静脉注射脂多糖之前5d,每天以植物油灌胃（0.5ml/kg·次）1次，注射脂多糖后立即经腹腔注射植物油（1ml/kg）；ATRA干预组在尾静脉注射脂多糖之前5d，每天以含有30mg/kg ATRA的植物油灌胃（0.5ml/kg·次）1次，注射脂多糖后立即经腹腔注射含5mg/kg ATRA的植物油（1ml/kg）；对照组在整个实验过程中均采用生理盐水（0.5ml/kg）以同样的方式进行对照处理。腹腔注射ATRA8h后处死3组大鼠，并测定每只大鼠动脉血样分压（PaO2）、支气管肺泡灌洗液（Bronchial alveolar lavage fluid，BALF）中蛋白含量以及肺组织湿/干比重（Wet/Dry，W/D），显微镜下观察肺组织苏木精-伊红(Hematoxylin-eosin,HE)染色情况，并采用RT-PCR、蛋白印迹（westernblot，WB）及免疫组化检测肺组织中MMP-9基因mRNA及蛋白的表达。结果ALI组大鼠肺组织炎性细胞与对照组比较明显增多，，动脉PaO2明显下降（P0.05）,W/D、BALF中蛋白含量、肺组织中MMP-9基因mRNA及蛋白含量均明显升高（P0.05）；与ALI组相比，干预组模型肺组织炎症反应明显改善，W/D、BALF中蛋白含量、肺组织中MMP-9基因mRNA及蛋白表达水平明显下降（P0.05或P0.01），其动脉PaO2亦有所改善（P0.05）。结论MMP-9可能参与ALI的炎性过程，ATRA对脂多糖所致ALI具有治疗作用，其机制可能是通过降低MMP-9的表达所实现的。
[Abstract]:Objective to study the changes of matrix metalloproteinase-9 (MMP-9) and its related inflammatory markers in rats with acute lung injury induced by lipopolysaccharide (LPS) and the effect of all-trans retinonic acidar on the expression of matrix metalloproteinase-9 (MMP-9) in rats with acute lung injury induced by lipopolysaccharide (LPS). To investigate the therapeutic effect of all-trans retinoic acid (ATRA) on pulmonary inflammation in acute lung injury. Methods Thirty SD rats were randomly divided into three groups: saline control group and ATRA intervention group. Acute lung injury model was established in the latter two groups by injecting lipopolysaccharide (LPS) 5 ml / kg into the tail vein. In the Ali group, 0.5 ml / kg of vegetable oil was injected into the stomach 5 days before lipopolysaccharide was injected into the tail vein. Immediately after lipopolysaccharide was injected intraperitoneally, 1 ml / kg of vegetable oil was injected intraperitoneally in the intervention group, 5 days before injection of lipopolysaccharide into caudal vein, 0.5 ml / kg of vegetable oil containing 30mg/kg ATRA was injected into the stomach of the intervention group once a day. Immediately after lipopolysaccharide injection, 1 ml / kg 5mg/kg ATRA containing vegetable oil was injected intraperitoneally, while the control group was treated in the same way with normal saline 0.5 ml / kg. Three groups of rats were killed after intraperitoneal injection of ATRA8h. The protein content of Pao _ 2 and bronchoalveolar alveolar lavage were measured in each rat, and the wet / dry specific gravity of lung tissue (Wet / Dryster / WDV) was measured. The staining of hematoxylin-eosinine (HEH) in lung tissue was observed under microscope. The expression of MMP-9 gene mRNA and protein in lung tissue was detected by RT-PCR (Western blotl) and immunohistochemistry. Results compared with the control group, the inflammatory cells of lung tissue in ALI group increased significantly, and the content of PaO2 in arterial PaO2 decreased significantly, while the protein content of MMP-9 gene mRNA and protein in lung tissue increased significantly, compared with that of ALI group, compared with ALI group, the content of MMP-9 gene mRNA and protein in lung tissue of ALI group was significantly higher than that of ALI group. In the intervention group, the inflammatory reaction of lung tissue significantly improved the protein content in the lung tissue, and the expression of MMP-9 gene mRNA and protein in the lung tissue decreased significantly (P0.05 or P0.01), and the arterial PaO2 also improved P0.05. Conclusion MMP-9 may be involved in the inflammatory process of ALI. ATRA may be involved in the treatment of ALI induced by lipopolysaccharide, and its mechanism may be by decreasing the expression of MMP-9.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R563.8

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