生长激素对急性肺损伤大鼠CC16表达的调控

Regulation on the expression of CC16 in acute lung injury rats’ lung by growth hormone

目的研究生长激素(GH)对内毒素血症所致急性肺损伤(ALI)的影响及机制。方法112只雄性SD大鼠内毒素致急性肺损伤后随机均分为ALI组和GH组。分别用Western blot法、免疫荧光法和半定量RT-PCR法测定大鼠肺组织中CC16蛋白含量、核因子NF-κB的表达与活化、CC16mRNA的表达水平,并分析CC16与肺损伤程度及NF-κB等炎性因子之间的关系。结果内毒素致伤后6小时内ALI组大鼠CC16mRNA表达水平及CC16蛋白含量均进行性下降,6小时后逐渐恢复。致伤后GH组大鼠肺组织CC16mRNA水平和CC16蛋白水平均较ALI组同时相点下降更明显。NF-κB表达、活化的变化趋势与CC16的变化趋势相反。相关性分析显示,CC16与肺损伤程度及NF-κB等炎性因子显著相关。结论CC16表达变化在内毒素血症致急性肺损伤的发病中有重要作用,生长激素可通过下调肺源性抗炎因子CC16的表达而加剧内毒素血症所致的急性肺损伤。

Objective：To study the effect of growth hormone （GH） on acute lung injury induced by endotoximia and its＇ mechanism. Methods：After introduction of acute lung injury （ALI） by endotoximia, one hundred and tweleve male Sprague-Dawley rats were randomly divided into ALI group and GH group. Western blot,immunofluorescence staining and semi-quantitive reverse transcription polymerase chain reaction（RT-PCR） were used to determine the expression and activation of nuclear factor kappa B（ NF-κB）, the levels of CC16 protein and the expression levels of CC16 mRNA in ALI rats＇ lung. Results：Both the expression levels of CC16 mRNA and the contents of CC16 protein in ALI rats＇ lungs began to decrease significantly 0.5 h post-injury,reached nadir at 6 h post-injury, and then began to recover. Both the expression levels of CC16 mRNA and the contents of CC16 protein in GH group were significantly lower than those in ALI group at different time intervals post-injury. The dynamic changes of the expression and activation of NF-κB were contrast to those of CC16 protein levels. Correlation analysis indicated that CC16 correlates significantly with the extent of lung injury and the expression and activation of NF-κB. Conclusion：Down-regulation of CC16 expression plays a critical role in the pathogenesis of acute lung injury induced by endotoximia. The application of GH can deteriorate the lung injury induced by endotoximia through down-regulating the expression of CC16.