摘要
目的 探讨生物喋呤对内毒素休克大鼠肺组织核转录因子 κB (NF κB)通路活化的影响及其在急性肺损伤中的意义。方法 采用内毒素休克模型 ,10 4只大鼠分为正常对照组 (n =8)、内毒素休克组(n =4 8)、 2 ,4 二胺 6 羟基嘧啶 (2 ,4 diamino 6 hydroxy apyrimidine ,DAHP)拮抗组 (n =4 8)。采用逆转录多聚酶链式反应测定肺组织三磷酸鸟苷环水解酶I (GTP CHI)mRNA的表达水平 ,采用凝胶阻滞电泳分析技术测定NF κB的DNA结合活性 ,同时测定肺组织髓过氧化物酶 (MPO)活性。结果 与正常对照组相比 ,内毒素攻击可导致动物肺组织GTP CHImRNA表达明显上调 ,6h后一直维持在较高水平 ;同时 ,NF κB活性于 0 5h迅速增加 ;且持续至伤后 4 8h ,肺组织MPO活性各时间点均显著升高 (P <0 .0 1) ,6h达峰值。采用生物喋呤合成抑制剂DAHP处理后 ,肺组织GTP CHImRNA表达早期改变不明显 ,但 12h后明显受抑 ;MF κB活性 0 5、 2 4、 4 8h明显降低 ;肺组织MPO活性 0 5、 6、 2 4、 4 8h均显著低于内毒素休克组 (P <0 0 5 )。结论 生物喋呤参与了内毒素休克动物肺组织NF κB信号通路的活化过程 ,抑制生物喋呤能降低NF κB的DNA结合活性 。
Objective To investigate the effect of biopterin on activation of nuclear factor-kappaB(NF-κB) signal transduction pathway in lung tissue,and to explore its significance.Methods Endotoxic shock model was used.104 male Wistar rats were divided into normal control group(n=8),endotoxic shock group(n=48),2,4-diaminto-6-hydroxy-pyrimidine(DAHP)treatment group(n=48).Guanosine triphosphat-cyclohydrolase(GTP-CHI)mRNA expression was semi-quantitative determined by reverse-transcription polymerase chain reaction (RT-PCR).Activity of NF-κΒ was assayed by electrophoretic mobility shift assay (EMSA),and pulmonary myeloperoxidase(MPO)activity was also determined.Results Compared with normal control group,GTP-CHI mRNA expression in lung tissue was markedly up-regulated and maintained at relatively high level from 6 h to 48 h after endotoxin challenge.The activation of NF-κB was enhanced rapidly at 0.5 h and maintainned at high level up to 48 h.Pulmonary MPO activity was significantly elevated(P<0.01) and peaked at 6h after endotoxin challgnge in endotoxic shock group.In DAHP group,an inhibitor of tetrahydrobiopterin synthesis inhibited GTP-CHI mRNA expression evidently 12h after the treatment,compared with endotoxic shock group,but there was no change during early period.NF-κB activities decreased at 0.5,24,48h,and MPO activities were significantly reduced in DAHP group.Conclusion Biopterin may be involved in the activation of NF-κB signal transduction pathway in lung tissue with endotoxic shock.Early treatment duing DAHP can inbibit pulmonary NF-κB activation and attenuate endotoxin-induced acute lung injury.
出处
《中华急诊医学杂志》
CAS
CSCD
2003年第10期667-669,T001,共4页
Chinese Journal of Emergency Medicine
基金
国家重点基础研究发展规划项目 (G19990 5 42 0 3 )
国家杰出青年基金资助项目 (3 0 12 5 0 2 0 )
国家自然科学基金资助项目 (3 9870 2 86
3 0 2 0 0 2 93 )
