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스테로이드제 투여 후 친수성과 공수성 표면활성물질 단백의 전사 신장도 비교

The comparative assessment of nuclear run on of hydrophilic and hydrophobic surfactant protein by administration of steroid

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목적 : 표면활성물질은 급성호흡곤란증후군의 병태생리와 밀접한 관계를 갖고 있으며, 표면활성물질 단백은 표면활성물질의 물리적 성상의 결정 및 대사를 결정하는데 있어서 중요한 역할을 한다. 전사 신장도 분석은 클론 유전자가 전사에 의해 조절되는지를 알기 위하여 시행된다. 신장도 분석은 생체에서 이미 시작된 초기의 mRNA 쇄를 시험관 내에서 신장도를 정량측정하는 것이다. 쥐를 포함한 실험동물과 시험관 내에서 SP-A 발현에 대한 덱사메타손의 효과는 자극적이며, 표면활성물질 아포단백 유전자의 전사속도에 직접적인 자극효과를 미친다. 시험관 내에서의 실험을 통하여 관찰한 바에 의하면 글루코코르티코이드를 투여한 후에 SP-B mRNA와 SP-C mRNA은 증가한다. 그러나 동물실험에서 표면활성물질 단백의 전사 신장도에 대한 스테로이드제의 효과에 관한 보고는 찾아보기 어렵다. 실험동물에서의 현상을 파악하고자 백서에 덱사메타손을 투여한 후 전사 신장도 방법으로 친수성과 배수성 표면활성물질 단백의 유전자의 전사 속도를 비교 하기 위하여 이 연구를 시행하였다.

Abstract

Background : Surfactant proteins are important in the regulation of the surfactant secretion, synthesis and recycling. Glucocorticoids are known to have primary or secondary effects on gene expression and can alter the rate of gene transcription. The hydrophilic and hydrophobic surfactant protein have been shown to be upregulated by glucocorticoids in vitro but its regulation in vivo, however, is not well established. The authors carried out nuclear run on assays to determine wheather glucocorticoids altered the transcription rate of SP-A, SP-B and SP-C genes. Methods : Adult rats were given the 2 mg/kg dose of subcutaneous dexamethasone for 2 days and sacrified at 2 days. The transcription rate of SP-A, SP-B and SP-C genes were measured by nuclear run on assays. Results : Treatment with 2 mg/kg dexamethasone increased transcription of SP-A gene (1.6-fold) and SP-C gene (1.3-fold) compared to the control for SP-A and SP-C after 2 days, which were not statistically significant. The rate of gene transcription for SP-B at 2 days after 2 mg/kg dexamethasone administration was significantly increased by 5.3-fold compared to the control for SP-B (p<0.005). The rates of gene transcription for hydrophilic and hydrophobic surfactant proteins, even in the hydrophobic surfactant proteins SP-B and SP-C were different. Coclusions : The authors conclude that the difference in dexamethasone sensitivity may indicate that the three surfactant protein genes contain glucocorticoid response elements with different affinities for receptor in vivo.(Korean J Med 70:53-60, 2006)

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