白藜芦醇减轻COPD内质网应激诱导的肺泡上皮细胞凋亡研究

发布时间：2018-02-04 21:53

本文关键词： 慢性阻塞性肺疾病白藜芦醇内质网应激细胞凋亡肺泡上皮细胞　出处：《中南大学》2013年硕士论文　论文类型：学位论文

【摘要】：目的：探索白藜芦醇在慢性阻塞性肺疾病大鼠模型中减轻内质网应激所致肺泡上皮细胞凋亡的作用。方法：48只雄性SD大鼠,随机数字表法分为4组,COPD组用香烟烟熏+气管内滴注脂多糖方法复制COPD模型,赋形剂0.5%羧甲基纤维素钠灌胃。白藜芦醇干预组(COPD+Res组)构建COPD模型并白藜芦醇25mg/(kg.d)灌胃,正常对照组(Control组)予气管内滴注生理盐水100ul及赋形剂灌胃,白藜芦醇对照组(Res组)予气管内滴注生理盐水100ul并白藜芦醇25mg/kg灌胃。造模结束行肺功能检查,观察肺组织的病理改变,免疫组化和western-blot检测肺组织内质网应激特异性标志和凋亡分子CHOP、Caspase12表达,TUNEL法检测肺泡上皮细胞凋亡。结果：1. COPD组大鼠较Control组FEV0.3/FVC (%)、动态肺顺应性(Cdyn)均明显降低,气道阻力(RI)明显增高(均P0.05),COPD+Res组较COPD组FEV0.3/FVC (%)、Cdyn增高,RI下降(均P0.05)。2.COPD组肺组织病理见明显气道炎症和肺气肿改变,COPD+Res组气道炎症、肺气肿程度较COPD组减轻。3.CHOP、 Caspase12主要表达于肺泡上皮细胞和肺泡巨噬细胞中,COPD组积分光密度(IOD)值较Control组显著增高(均P0.05)；COPD+Res组IOD值较COPD组明显下降(均P0.05)。4.Western-blot显示COPD组与Control组相比肺组织中CHOP、active-Caspase12蛋白表达增加,CHOP/β-actin、active-Caspase12/β-actin吸光度值比值显著增高(均P0.05); COPD+Res组上述指标较COPD组下降(均P0.05)。5.TUNEL检测显示COPD组肺泡上皮细胞凋亡指数(AI)较Control组显著增高(P0.05)；COPD+Res组肺泡上皮细胞AI较COPD组降低。结论：COPD大鼠肺组织发生了内质网应激诱导的肺泡上皮细胞等结构细胞凋亡,白藜芦醇可减轻内质网应激诱导的肺泡上皮细胞凋亡。
[Abstract]:Aim: to investigate the role of resveratrol in alleviating the apoptosis of alveolar epithelial cells induced by endoplasmic reticulum stress in rats with chronic obstructive pulmonary disease (COPD). Methods Forty-eight male Sprague-Dawley rats were randomly divided into 4 groups. The COPD model was induced by cigarette fumigation and intratracheal instillation of lipopolysaccharide (LPS). Excipient 0.5% carboxymethyl cellulose sodium intragastric perfusion. Resveratrol intervention group (Res group) to build COPD model and resveratrol 25 mg / kg 路d). Normal control group (control group) was given intratracheal infusion of normal saline 100ul and excipient intragastric administration. Resveratrol control group (res group) was given intratracheal infusion of normal saline 100ul and resveratrol 25mg / kg intragastrically. Pulmonary function was examined at the end of the model and the pathological changes of lung tissue were observed. Immunohistochemistry and western-blot were used to detect the expression of endoplasmic reticulum stress-specific markers and apoptotic molecule CHOP-Caspase12 in lung tissue. Apoptosis of alveolar epithelial cells was detected by TUNEL method. Results 1. The dynamic lung compliance of COPD group was significantly lower than that of Control group. The airway resistance (RI) was significantly higher in Res group than that in COPD group (P 0.05). RI decreased (P0.05. 2. There were obvious airway inflammation and emphysema change in Res group. Compared with COPD group, the degree of emphysema decreased. 3. CHOP. Caspase12 was mainly expressed in alveolar epithelial cells and alveolar macrophages. The integral optical density (IOD) of COPD group was significantly higher than that of Control group (P 0.05). The IOD value of COPD Res group was significantly lower than that of COPD group (all P 0.05). 4. Western-blot analysis showed that CHOP in lung tissue of COPD group was higher than that of Control group. The expression of active-Caspase12 protein increased the expression of CHOP- 尾 -actin. The absorbance ratio of active-Caspase12 / 尾 -actin increased significantly (all P 0.05). The above indexes in COPD Res group were lower than those in COPD group (all P0.05n.5. Tunel showed that the apoptosis index of alveolar epithelial cells in COPD group was higher than that in COPD group). Compared with Control group, it was significantly higher than that of Control group (P 0.05). The AI of alveolar epithelial cells in COPD Res group was lower than that in COPD group. Conclusion the endoplasmic reticulum stress induced apoptosis of alveolar epithelial cells was observed in lung tissue of rats with COPD. Resveratrol can reduce the apoptosis of alveolar epithelial cells induced by endoplasmic reticulum stress.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R563.9;R285.5

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