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地塞米松对新生鼠高氧肺损伤肺组织甲状腺转录因子-1和表面活性蛋白C表达的影响

Effect of dexamethasone on the expression of thyroid transcription factor-1(TTF-1) and surfactant protein C(SPC) in neonatal rats with hyperoxia lung injury
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摘要 目的探讨甲状腺转录因子-1(TTF-1)和表面活性蛋白C(SPC)在地塞米松干预新生鼠高氧肺损伤中的作用。方法将3日龄新生SD大鼠随机分为高氧组(95%氧7 d)、高氧+地塞米松组(地塞米松组)和空气组。HE染色观察肺组织形态结构变化,并做辐射状肺泡计数(RAC)。采用免疫组化法检测肺组织TTF-1和SPC表达。结果(1)高氧组可见肺泡壁较薄、结构简单化、肺泡大小不均,有些肺泡融合、体积增大;地塞米松组除具有上述高氧组特征外,肺组织结构明显紊乱,部分肺泡壁及间隔破坏;高氧组和地塞米松组RAC值分别为(9.50±1.05)、(10.03±3.26),较空气组(13.00±1.79)减少,差异均有显著性(P<0.05)。(2)空气组TTF-1阳性显色细胞分布在肺间隔和肺泡壁II型肺泡上皮细胞(AECII),无扩张肺组织处也有阳性细胞,各级支气管及小血管部位未见阳性显色。高氧组较空气组表达减少,散在分布于肺泡壁、肺间隔增厚部位及脱落于肺泡腔的AECII;地塞米松组较空气组明显增强,变薄及扩张的肺泡壁也有阳性显色。空气组、高氧组、地塞米松组TTF-1表达积分分别为(1.32±0.55)、(0.96±0.67)、(1.76±0.69),高氧组较地塞米松组和空气组明显减少,差异有显著性(P均<0.05);而地塞米松组较空气组明显增高,差异有显著性(P<0.05)。(3)SPC阳性显色主要在肺间隔和肺泡壁AECII,支气管黏膜上皮细胞也可见弱阳性表达,但存在个体差异,有些标本整个切片未见表达。高氧组、地塞米松组和空气组SPC表达积分差异无显著性,分别为(1.58±0.49)、(1.52±0.50)、(1.66±0.48),P>0.05。结论(1)SPC不仅在AECII表达,也表达在支气管黏膜上皮细胞;在高氧肺损伤及地塞米松干预肺组织SPC表达变化不大,有可能是AECII增殖、分化不足的反映。(2)高氧肺损伤组织TTF-1表达减少,地塞米松可使TTF-1表达增强,加重肺部病理改变。 Objective To investigate the effect of TTF-1 and SPC on Lung injury induced by hyper- oxia in neonatal rats treated with dexamethasone. Methods 3-day-old Sprague-Dawley neonatal rats were ran- domized divided into hypemxia group(exposed to 95 % oxygen for 7 days), dexamethasone group(exposed to 95% oxygen for 7 days and intraabdominally injected dexamethasone of 1 μg/g on the first day) and air group. Lung histological study and radical alveoli count(RAC) were performed by HE staining. The expres- sions of TTF-1 and SPC were detected with immunohistochemical method. Results (1) The neonatal rats lungs of hyperoxia group showed thinner walls of alveoli, simple alveolar structure, fewer and larger alveoli, expanded and shrinked alveoli, the rats with dexamethasone showed more severe pathlogical changes including structure turbu- lence of pulmonary tissue, some destroyed septa and walls of alveoli. RAC of hyperoxia group and dexamethasone group were (9.50 - 1.05) and ( 10.03 - 3.26), respectively, which were significantly dereased than that of air group (13.00±1.79)(P〈0.05). (2) TTF-1 positive cells located in AECII of septa, wall of alveoli, and the non-inflated tissues. The TTF-1 expression score Was less in hyperoxia group(0.96±0.67) than in air group( 1.32±0.55 )( P 〈 0.05 ), but more in dexamethasone group( 1.76±0.69 ) than in air group( P 〈 0.05). (3) The SPC positive cells lo- cated in AECII of septa and walls of alveoli, as well as bronchiolar epithelium. There was no significant difference in SPC expression score among three groups ( 1.58±0.49 ) vs ( 1.52±0.50 ) vs ( 1.66±0.48 ) ( P 〉 0.05 ). Conclmion SPC was expressed not only by AECII, but also bronchiolar epithelium. The expression level of SPC af- ter hyperoxia exposion has no significant increase reflecting the decreasing ability of proliferation and differentiation in AECII. There is a decreased expression of TTF-1 after hyperoxia exposion, while dexamethasone may aggravate lung injury by excessly up-regulating TTF-1 expression.
出处 《中国小儿急救医学》 CAS 2007年第5期420-424,469,共6页 Chinese Pediatric Emergency Medicine
基金 国家自然科学基金资助项目(30571967)
关键词 地塞米松 新生鼠 高氧肺损伤 肺组织 甲状腺转录因子-1 表面活性蛋白C 表达 Hyperoxia lung injury Thyroid transcription factor-1 Surfactant protein C Dexamethasone
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