目的研究尿激酶型纤溶酶原激活物(u-PA)基因对小鼠实验性老年性肺气肿样改变的影响及其机制。方法取15d及4月龄野生型小鼠和u-PA基因敲除小鼠肺组织,HE、Weigert弹力纤维染色比较不同基因型小鼠肺组织形态,Image Pro Plus软件分析u-PA...目的研究尿激酶型纤溶酶原激活物(u-PA)基因对小鼠实验性老年性肺气肿样改变的影响及其机制。方法取15d及4月龄野生型小鼠和u-PA基因敲除小鼠肺组织,HE、Weigert弹力纤维染色比较不同基因型小鼠肺组织形态,Image Pro Plus软件分析u-PA基因缺失对肺组织弹力纤维蛋白含量的影响,并采用Real-time PCR检测肺组织间质成份表达水平。结果15d鼠龄u-PA基因缺失小鼠相比野生型(WT)小鼠肺组织形态无明显差异;弹力纤维含量、弹力蛋白基因表达、MMP-12基因表达无显著差异;4月龄u-PA基因缺失小鼠肺泡壁结构较野生型小鼠完整,肺泡腔无明显增大;肺泡弹力纤维含量、肺组织弹力蛋白基因表达及TIMP-1基因的表达显著高于野生型小鼠,MMP-12基因表达也略有增高。结论u-PA基因缺失能够减轻小鼠实验性老年性肺气肿样改变,其分子机制可能是u-PA基因缺失后,弹力蛋白和TIMP-1基因的表达增加,导致肺组织弹力纤维含量增加。展开更多
Chronic obstructive pulmonary disease(COPD) is characterized by the presence of airflow limitations that are not fully reversible and is a major cause of chronic morbidity and mortality worldwide. Although there has b...Chronic obstructive pulmonary disease(COPD) is characterized by the presence of airflow limitations that are not fully reversible and is a major cause of chronic morbidity and mortality worldwide. Although there has been extensive research examining the molecular mechanisms underlying the development of COPD, there is no proven clinically effective treatment for promoting recovery from established COPD. At present, regeneration is the only hope for a cure in patients with COPD. In this article, we review current treatments for COPD, focusing particularly on recent advances in lung regeneration based on two major approaches: regeneration-promoting agents and cell therapy. Retinoic acids are the majorfocus among regeneration-promoting agents, while mesenchymal stem cells are the main topic in the field of cell-based therapy. This article aims to provide valuable information for developing new therapies for COPD.展开更多
Background The decrease of surfactant protein （SP） secreted by the alveolar type Ⅱ cell is one of the important causes of limiting air of pulmonary emphysema. However, the SP-A gene and protein changes in this dise...Background The decrease of surfactant protein （SP） secreted by the alveolar type Ⅱ cell is one of the important causes of limiting air of pulmonary emphysema. However, the SP-A gene and protein changes in this disease are rarely studied. This study was undertaken to investigate alterations in SP-A gene activity and protein, and to explore their roles in the pathogenesis of emphysematous changes. Methods Twenty Wistar rats were divided randomly into a normal control group （n=10） and a cigarette smoking （CS） ＋ lipopolysaccharide （LPS） group （n=10）. Ultra-structural changes were observed under an electron microscope. The number of cells positive for SP-A was measured by immunohistochemistry. The mRNA expression and protein level of SP-A in the lung tissues were determined by quantitative polymerase chain reaction （qPCR） and Western blot separately. The protein level of SP-A in lavage fluid was determined by Western blot. Results The number of cells positive for SP-A of the CS＋LPS group （0.35±0.03） was lower than that of the blank control group （0.72±0.06, P 〈0.05）. The level of SP-A in the lung tissues of rats in the CS＋LPS group （0.2765±0.0890） was lower than that in the blank control group （0.6875±0.1578, P 〈0.05）. The level of SP-A in the lavage fluid of rats in the CS＋LPS group （0.8567±0.1458） was lower than that in the blank control group （1.3541±0.2475, P 〈0.05）. The lung tissues of rats in the CS＋LPS group showed an approximate increase （0.4-fold） in SP-A mRNA levels relative to β-actin mRNA （P 〈0.05）. Conclusions The changes of SP-A may be related to emphysematous changes in the lung. And cigarette smoke and LPS alter lung SP-A gene activity and protein homeostasis.展开更多
文摘目的研究尿激酶型纤溶酶原激活物(u-PA)基因对小鼠实验性老年性肺气肿样改变的影响及其机制。方法取15d及4月龄野生型小鼠和u-PA基因敲除小鼠肺组织,HE、Weigert弹力纤维染色比较不同基因型小鼠肺组织形态,Image Pro Plus软件分析u-PA基因缺失对肺组织弹力纤维蛋白含量的影响,并采用Real-time PCR检测肺组织间质成份表达水平。结果15d鼠龄u-PA基因缺失小鼠相比野生型(WT)小鼠肺组织形态无明显差异;弹力纤维含量、弹力蛋白基因表达、MMP-12基因表达无显著差异;4月龄u-PA基因缺失小鼠肺泡壁结构较野生型小鼠完整,肺泡腔无明显增大;肺泡弹力纤维含量、肺组织弹力蛋白基因表达及TIMP-1基因的表达显著高于野生型小鼠,MMP-12基因表达也略有增高。结论u-PA基因缺失能够减轻小鼠实验性老年性肺气肿样改变,其分子机制可能是u-PA基因缺失后,弹力蛋白和TIMP-1基因的表达增加,导致肺组织弹力纤维含量增加。
文摘Chronic obstructive pulmonary disease(COPD) is characterized by the presence of airflow limitations that are not fully reversible and is a major cause of chronic morbidity and mortality worldwide. Although there has been extensive research examining the molecular mechanisms underlying the development of COPD, there is no proven clinically effective treatment for promoting recovery from established COPD. At present, regeneration is the only hope for a cure in patients with COPD. In this article, we review current treatments for COPD, focusing particularly on recent advances in lung regeneration based on two major approaches: regeneration-promoting agents and cell therapy. Retinoic acids are the majorfocus among regeneration-promoting agents, while mesenchymal stem cells are the main topic in the field of cell-based therapy. This article aims to provide valuable information for developing new therapies for COPD.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30500224, 3040199）.
文摘Background The decrease of surfactant protein （SP） secreted by the alveolar type Ⅱ cell is one of the important causes of limiting air of pulmonary emphysema. However, the SP-A gene and protein changes in this disease are rarely studied. This study was undertaken to investigate alterations in SP-A gene activity and protein, and to explore their roles in the pathogenesis of emphysematous changes. Methods Twenty Wistar rats were divided randomly into a normal control group （n=10） and a cigarette smoking （CS） ＋ lipopolysaccharide （LPS） group （n=10）. Ultra-structural changes were observed under an electron microscope. The number of cells positive for SP-A was measured by immunohistochemistry. The mRNA expression and protein level of SP-A in the lung tissues were determined by quantitative polymerase chain reaction （qPCR） and Western blot separately. The protein level of SP-A in lavage fluid was determined by Western blot. Results The number of cells positive for SP-A of the CS＋LPS group （0.35±0.03） was lower than that of the blank control group （0.72±0.06, P 〈0.05）. The level of SP-A in the lung tissues of rats in the CS＋LPS group （0.2765±0.0890） was lower than that in the blank control group （0.6875±0.1578, P 〈0.05）. The level of SP-A in the lavage fluid of rats in the CS＋LPS group （0.8567±0.1458） was lower than that in the blank control group （1.3541±0.2475, P 〈0.05）. The lung tissues of rats in the CS＋LPS group showed an approximate increase （0.4-fold） in SP-A mRNA levels relative to β-actin mRNA （P 〈0.05）. Conclusions The changes of SP-A may be related to emphysematous changes in the lung. And cigarette smoke and LPS alter lung SP-A gene activity and protein homeostasis.
