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低分子肝素對(duì)COPD模型大鼠肺組織低氧誘導(dǎo)因子-1、血紅素加氧酶-1、血管內(nèi)皮生長(zhǎng)因子表達(dá)的影響

發(fā)布時(shí)間:2018-04-27 11:01

  本文選題:HIF-1 + VEGF; 參考:《青島大學(xué)》2012年碩士論文


【摘要】:目的研究COPD模型大鼠肺組織中低氧誘導(dǎo)因子-1(HIF-1)、血管內(nèi)皮生長(zhǎng)因子(VEGF)、血紅素加氧酶-1(HO-1)的表達(dá)及低分子肝素干預(yù)對(duì)其影響。 方法將60只清潔級(jí)Wistar大鼠隨機(jī)分為3組:①對(duì)照組(n=20):給予氣管內(nèi)注入生理鹽水,皮下注射生理鹽水;②OPD模型組(n=20):模型組采用煙熏聯(lián)合氣管內(nèi)注入脂多糖的方法建立COPD動(dòng)物模型,給予生理鹽水皮下注射,1次/日;③低分子肝素干預(yù)組(n=20):LMWH組在建立COPD模型同時(shí)給予皮下注射低分子肝素干預(yù),1次/日。觀察三組血?dú)庵笜?biāo)、肺泡灌洗液中細(xì)胞數(shù)及分類、肺組織病理形態(tài)學(xué)變化,并應(yīng)用免疫組化的方法檢測(cè)LMWH干預(yù)前后肺組織中HIF-、HO-、VEGF的表達(dá)情況,并分析該三種因子與中性粒細(xì)胞數(shù)間的相關(guān)性。 結(jié)果血?dú)夥治鍪九c對(duì)照組相比,LMWH干預(yù)組及COPD模型組PaO2下降,PaCO2升高且均有顯著性差異(P0.05),LMWH干預(yù)組較COPD模型組PaO2升高,PaCO2下降,均有顯著性差異(P0.05);LMWH干預(yù)組及COPD模型組BALF中白細(xì)胞總數(shù)及中性粒細(xì)胞百分比較對(duì)照組相比升高,(P0.05),LMWH干預(yù)組BALF中白細(xì)胞總數(shù)及中性粒細(xì)胞百分比較COPD模型組減少,差異均有統(tǒng)計(jì)學(xué)意義(P0.05);建立的COPD大鼠模型的肺組織病理學(xué)改變基本符合人類COPD組織病理學(xué)改變特點(diǎn),LMWH干預(yù)組肺組織病理改變較COPD組減輕;LMWH干預(yù)組及COPD模型組較對(duì)照組MLI、PAA增高,MAN減少,具有顯著性差異(P0.05),LMWH干預(yù)組較COPD模型組相比,MLI及PAA減小,MAN增大,差異有統(tǒng)計(jì)學(xué)意義(P0.05);免疫組化結(jié)果示COPD組及LMWH組HIF-、VEGF及HO-1在大鼠肺組織中的表達(dá)均較對(duì)照組增加,但與COPD模型組相比,LMWH干預(yù)組肺組織的病理改變較輕,HIF-、VEGF及HO-1表達(dá)減弱;經(jīng)相關(guān)分析,HIF-、HO-1、VEGF與中性粒細(xì)胞之間成正相關(guān),r分別為0.86、0.82、0.89,(P0.05)。 結(jié)論HIF-1、VEGF、HO-1均參與氣道炎癥;低分子肝素可以減輕氣道炎癥。
[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.
【學(xué)位授予單位】:青島大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類號(hào)】:R563.9

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