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白藜蘆醇減輕COPD內(nèi)質(zhì)網(wǎng)應(yīng)激誘導(dǎo)的肺泡上皮細(xì)胞凋亡研究

發(fā)布時(shí)間:2018-02-04 21:53

  本文關(guān)鍵詞: 慢性阻塞性肺疾病 白藜蘆醇 內(nèi)質(zhì)網(wǎng)應(yīng)激 細(xì)胞凋亡 肺泡上皮細(xì)胞 出處:《中南大學(xué)》2013年碩士論文 論文類(lèi)型:學(xué)位論文


【摘要】:目的:探索白藜蘆醇在慢性阻塞性肺疾病大鼠模型中減輕內(nèi)質(zhì)網(wǎng)應(yīng)激所致肺泡上皮細(xì)胞凋亡的作用。 方法:48只雄性SD大鼠,隨機(jī)數(shù)字表法分為4組,COPD組用香煙煙熏+氣管內(nèi)滴注脂多糖方法復(fù)制COPD模型,賦形劑0.5%羧甲基纖維素鈉灌胃。白藜蘆醇干預(yù)組(COPD+Res組)構(gòu)建COPD模型并白藜蘆醇25mg/(kg.d)灌胃,正常對(duì)照組(Control組)予氣管內(nèi)滴注生理鹽水100ul及賦形劑灌胃,白藜蘆醇對(duì)照組(Res組)予氣管內(nèi)滴注生理鹽水100ul并白藜蘆醇25mg/kg灌胃。造模結(jié)束行肺功能檢查,觀(guān)察肺組織的病理改變,免疫組化和western-blot檢測(cè)肺組織內(nèi)質(zhì)網(wǎng)應(yīng)激特異性標(biāo)志和凋亡分子CHOP、Caspase12表達(dá),TUNEL法檢測(cè)肺泡上皮細(xì)胞凋亡。 結(jié)果:1. COPD組大鼠較Control組FEV0.3/FVC (%)、動(dòng)態(tài)肺順應(yīng)性(Cdyn)均明顯降低,氣道阻力(RI)明顯增高(均P0.05),COPD+Res組較COPD組FEV0.3/FVC (%)、Cdyn增高,RI下降(均P0.05)。2.COPD組肺組織病理見(jiàn)明顯氣道炎癥和肺氣腫改變,COPD+Res組氣道炎癥、肺氣腫程度較COPD組減輕。3.CHOP、 Caspase12主要表達(dá)于肺泡上皮細(xì)胞和肺泡巨噬細(xì)胞中,COPD組積分光密度(IOD)值較Control組顯著增高(均P0.05);COPD+Res組IOD值較COPD組明顯下降(均P0.05)。4.Western-blot顯示COPD組與Control組相比肺組織中CHOP、active-Caspase12蛋白表達(dá)增加,CHOP/β-actin、active-Caspase12/β-actin吸光度值比值顯著增高(均P0.05); COPD+Res組上述指標(biāo)較COPD組下降(均P0.05)。5.TUNEL檢測(cè)顯示COPD組肺泡上皮細(xì)胞凋亡指數(shù)(AI)較Control組顯著增高(P0.05);COPD+Res組肺泡上皮細(xì)胞AI較COPD組降低。 結(jié)論:COPD大鼠肺組織發(fā)生了內(nèi)質(zhì)網(wǎng)應(yīng)激誘導(dǎo)的肺泡上皮細(xì)胞等結(jié)構(gòu)細(xì)胞凋亡,白藜蘆醇可減輕內(nèi)質(zhì)網(wǎng)應(yīng)激誘導(dǎo)的肺泡上皮細(xì)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.
【學(xué)位授予單位】:中南大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2013
【分類(lèi)號(hào)】:R563.9;R285.5

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