低分子肝素对COPD模型大鼠肺组织低氧诱导因子-1、血红素加氧酶-1、血管内皮生长因子表达的影响

发布时间：2018-04-27 11:01

本文选题：HIF-1 + VEGF　；参考：《青岛大学》2012年硕士论文

【摘要】：目的研究COPD模型大鼠肺组织中低氧诱导因子-1(HIF-1)、血管内皮生长因子(VEGF)、血红素加氧酶-1(HO-1)的表达及低分子肝素干预对其影响。方法将60只清洁级Wistar大鼠随机分为3组：①对照组(n=20)：给予气管内注入生理盐水,皮下注射生理盐水；②OPD模型组(n=20)：模型组采用烟熏联合气管内注入脂多糖的方法建立COPD动物模型,给予生理盐水皮下注射,1次/日；③低分子肝素干预组(n=20)：LMWH组在建立COPD模型同时给予皮下注射低分子肝素干预,1次/日。观察三组血气指标、肺泡灌洗液中细胞数及分类、肺组织病理形态学变化,并应用免疫组化的方法检测LMWH干预前后肺组织中HIF-、HO-、VEGF的表达情况,并分析该三种因子与中性粒细胞数间的相关性。结果血气分析示与对照组相比,LMWH干预组及COPD模型组PaO2下降,PaCO2升高且均有显著性差异(P0.05),LMWH干预组较COPD模型组PaO2升高,PaCO2下降,均有显著性差异(P0.05)；LMWH干预组及COPD模型组BALF中白细胞总数及中性粒细胞百分比较对照组相比升高,(P0.05),LMWH干预组BALF中白细胞总数及中性粒细胞百分比较COPD模型组减少,差异均有统计学意义(P0.05)；建立的COPD大鼠模型的肺组织病理学改变基本符合人类COPD组织病理学改变特点,LMWH干预组肺组织病理改变较COPD组减轻；LMWH干预组及COPD模型组较对照组MLI、PAA增高,MAN减少,具有显著性差异(P0.05),LMWH干预组较COPD模型组相比,MLI及PAA减小,MAN增大,差异有统计学意义(P0.05)；免疫组化结果示COPD组及LMWH组HIF-、VEGF及HO-1在大鼠肺组织中的表达均较对照组增加,但与COPD模型组相比,LMWH干预组肺组织的病理改变较轻,HIF-、VEGF及HO-1表达减弱；经相关分析,HIF-、HO-1、VEGF与中性粒细胞之间成正相关,r分别为0.86、0.82、0.89,(P0.05)。结论HIF-1、VEGF、HO-1均参与气道炎症；低分子肝素可以减轻气道炎症。
[Abstract]:Objective to study the expression of hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF) and heme oxygenase-1 (HO-1) in lung tissue of COPD rats and the effects of low molecular weight heparin (LMWH) on them. Methods Sixty clean grade Wistar rats were randomly divided into 3 groups: control group (n = 3): control group (n = 3): normal saline was injected into trachea and normal saline was injected subcutaneously. 2OPD model group: COPD animal model was established by fumigation combined with endotracheal injection of lipopolysaccharide, and normal saline was injected subcutaneously once a day. 3 the low molecular weight heparin group (LMWH group) was given subcutaneous injection of low molecular weight heparin (LMWH) once a day to establish COPD model. The blood gas index, cell number and classification in alveolar lavage fluid, pathomorphology of lung tissue were observed, and the expression of HIF-HO-VEGF in lung tissue before and after LMWH intervention was detected by immunohistochemical method. The correlation between these three factors and neutrophils was analyzed. Results compared with the control group, the blood gas analysis showed that PaO2 decreased and Paco _ 2 increased in the LMWH intervention group and the COPD model group, and there was significant difference between the two groups (P < 0.05). Compared with the COPD model group, the PaO2 level in the LMWH intervention group was higher than that in the COPD model group. There were significant differences in the total number of leukocytes and the percentage of neutrophils in BALF in the P0.05LMWH intervention group and the COPD model group. Compared with the control group, the WBC and neutrophil percentage in the P0.05-LMWH intervention group was lower than that in the COPD model group. The lung histopathological changes of the COPD rat model were basically in line with the histopathological characteristics of human COPD. The lung histopathological changes of the LMWH intervention group were less than that of the COPD group and the COPD model group was better than that of the COPD group. In radiation group, MLI PAA increased and man decreased, There was significant difference in the expression of COPD and HO-1 in lung tissue of rats in COPD group and LMWH group, compared with COPD model group, the difference was statistically significant (P 0.05), the expression of HIF-VEGF and HO-1 in lung tissue of COPD group and LMWH group were higher than that of control group, and the difference was statistically significant compared with that of COPD model group, and the expression of HO-1 in lung tissue of COPD group and LMWH group was higher than that of control group. However, compared with the COPD model group, the pathological changes of the lung tissue in the LMWH intervention group were lower than that in the control group, and the positive correlation between HIF-HO-1 and neutrophils was 0.86 ~ 0.82 ~ (0.89) (P 0.05) respectively by correlation analysis between HIF-HO-1 and neutrophilic granulocytes. Conclusion HIF-1 VEGFHO-1 is involved in airway inflammation and low molecular weight heparin can attenuate airway inflammation.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R563.9

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