https://scholars.lib.ntu.edu.tw/handle/123456789/194461
標題: | 分析肺臟轉殖胎盤生長因子小鼠的肺臟發育(1/2) | 作者: | 曹伯年 | 關鍵字: | 早產兒慢性肺疾病;血管內皮細胞生長因子;血管新生蛋白;胎盤生長因子;Bronchopulmonary dysplasia;vascular endothelial growth factor;angiopoietin;placenta growth factor | 公開日期: | 2004 | 出版社: | 臺北市:國立臺灣大學醫學院小兒科 | 摘要: | 經過廣泛使用產前類固醇,肺部表面張力素治療,以及新生兒照顧技術的進步,極低 體重早產兒的存活率已大大的提高,但是早產兒慢性肺疾病卻仍然是早產兒的主要併發症之 一,其發生率約在百分之15 到50 之間。 早產兒慢性肺疾病的原因包括早產、長期的氧氣治療、呼吸器傷害、和感染。病理變 化包括肺泡發育不良、血管生長停滯、以及程度不等的纖維化。 從出生到成人階段,在肺泡的發育過程中,包括肺泡以及微血管表面積增加了約有20 倍之多。目前對於肺泡微血管大量增加的機轉仍不清楚,只知道肺泡微血管大量增加和肺泡 的形成有很大的關係。 在血管生成及血管新生的過程中,血管內皮細胞生長因子家族扮演著相當重要的角 色。目前已知早產兒慢性肺疾病的病人其肺臟除了血管發育不全外,血管內皮細胞生長因子 (VEGF)及其接受器(Flt-1)的表現量也明顯減少。至於,對於PlGF,另一個Flt-1 的受體(ligand), 在肺泡微血管的形成上所伴演的角色,目前則仍未被報告過。而在我們之前完成的PlGF 全身 過度表現的基因轉殖鼠中,我們發現它們外觀雖然看不出異常,但是它們的肺泡明顯有發育 不良的現象,足見PlGF 確實在肺臟的發育中扮演一重要角色。 為釐清PlGF 對肺臟發育的影響,今年我們已成功的利用肺臟獨特性的promoter,來讓 PlGF 只單純在肺臟過度表現的基因轉殖鼠。目前計畫進展順利,我們已按照計畫進度於第一 年成功建立肺臟獨特過度表現胎盤生長因子的基因轉殖鼠,並已往下繁殖四個不同基因表現 量的基因轉殖鼠。另外,我們亦已證實外加胎盤生長因子蛋白會促進肺臟上皮細胞死亡及抑 制其增生,顯見過量的胎盤生長因子對肺臟應有不好的影響。希望在接下來一年的計畫中, 能成功建立慢性肺疾病的動物模式。如此,不僅可讓我們瞭解PlGF 直接對肺臟發育的影響, 更可以利用此動物模式來探討肺泡發育的機轉,並進而找出治療早產兒慢性肺疾病的方法。 After the widespread use of antenatal steroid, exogenous surfactant therapy, and improvements in neonatal care, the survival rate of very low birth weight infants has increased, but bronchopulmonary dysplasia (BPD) persists as one of the major complications in premature infants who need prolonged ventilator support. The incidence of BPD ranges between 15 and 50%. The etiology of BPD included the immaturity, prolonged oxygen therapy, barotrauma, and infection. The pathological finding in the premature infants with BPD include alveolar hypoplasia, vascular arrest and adaptive dysmorphic changes, and variable interstitial proliferation. During the period of alveolarization, the lung also undergoes marked vascular growth as reflected by the 20-fold increase in alveolar and capillary surface areas from birth to adulthood. Mechanisms that increase vascular surface area during late gestation and the early postnatal period are poorly understood, but it is clear that coordination of distal air space and vascular growth is essential for normal lung development. Vascular endothelial growth factor (VEGF) family has been found to play an important role in vascuogenesis and angiogenesis. It has been well established that disrupted pulmonary vasculature and decreased VEGF and Flt-1, but no changes in Flk-1, in human infants dying with BPD. However, the role of PlGF, another ligand of Flt-1, in lung development is unknown. In our previous study, we found that overexpression of PlGF, using CMV promotor, seems disrupt pulmonary alveolarization. It give us a hint that PlGF may play an important role in lung development. In this year, we have used lung-specific promotor, SP-C (a gift from Dr. Whitsett, University of Cincinnati), to successfully generated four different SP-C-PlGF transgenic lines with different mRNA expression levels, confirmed by real time RT-PCR. In addition, we also demonstrated that exogenous recombinant PlGF promoted type II pneumocytes cell death and inhibited cell proliferation in vitro. In the next year, we will try to demonstrate the phenotype of this transgenic mouse and setup the animal model for chronic lung disease. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/22898 | 其他識別: | 922314B002222 | Rights: | 國立臺灣大學醫學院小兒科 |
顯示於: | 醫學系 |
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922314B002222.pdf | 118.66 kB | Adobe PDF | 檢視/開啟 |
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