内毒素休克大鼠生物喋呤改变与多器官损害的关系  

The relationship between biopterin formation and multiple organ dysfunction in rats with endotoxic shock

作　　者：姚咏明[1] 姚凤华[1] 彭志齐[2] 胥彩林[1] 于燕[1] 

机构地区：[1]解放军总医院第一附属医院全军烧伤研究所,北京100037 [2]解放军理工大学医院

出　　处：《中华急诊医学杂志》2006年第4期295-299,共5页Chinese Journal of Emergency Medicine

基　　金：国家重点基础研究发展规划项目(2005CB522602);国家自然科学基金资助项目(30200293);首都医学发展科研基金重点项目(2003-2023)

摘　　要：目的探讨内毒素休克动物肝、肺、肾等重要器官生物喋呤(BH4)变化规律及其与多器官损害的关系。方法采用内毒素休克模型。104只大鼠随机分为正常对照组(n=8)、内毒素休克组(n=48)和BH4合成抑制剂2,4二胺6羟基嘧啶(DAHP)拮抗组(n=48)。肝、肺、肾组织BH4含量用反相高效液相色谱法测定,组织三磷酸鸟苷环水解酶I(GTPCHI,BH4合成的首要限速酶)基因表达采用逆转录PCR方法检测。结果内毒素攻击后0.5～2h动物肝、肺、肾组织BH4含量即开始升高(P<0.05),6～12h达峰值(P<0.01),此后逐渐降低;同时,组织GTPCHImRNA表达均明显高于正常对照组(P<0.05)。给予DAHP处理后,2～24h肝、肺、肾组织BH4水平均显著低于内毒素休克组(P<0.05或0.01),肝、肾组织GTPCHImRNA表达各时相点亦明显下调,肺组织12h后降低至正常对照范围。反映肝、肾功能指标和肺组织髓过氧化物酶活性均有不同程度地下降(P<0.05或0.01)。结论生物喋呤参与了内毒素诱发组织损害的病理生理过程,抑制BH4合成有助于减轻脓毒性休克所致过度炎症反应和多器官功能损害。Objective To investigate the relationship between blopter/n formation and multiple organ dysfunction in rats with endotoxic shock. Methods A rat model of endotoxic shock was reproduced by a bolus injection of lipopolysaccharide （E. coli O55B5 LPS, 10 mg/kg, i. v.）. One hundred and four male Wistar rats were randomly divided into normal controls （ n = 8）, endotoxic shock group （ n = 48）, and 2, 4-diamino-6-hydroxy-pyrimidine （DAHP） treatment group （ n = 48）. At serial time points animals in each group were sacrificed, serum samples and tissue specimens from liver, lungs as well as kidneys were harvested. Tissue biopterin contents were measured by reverse-phase highperformance liquid chromatography/fluorescence detection. GTP cyclohydrolase I （GTP-CHI） mRNA expression was semiquantitatively determined by reverse-transcription polymerase chain reaction （RT-PCR） taking GAPDH as an internal standard. Results Compared to normal controls, tissue biopterin contents in liver, lungs and kidneys were markedly elevated at 0.5 to 2 hours after endotoxin challenge （ P 〈 0.05 or 0.01）, peaked at 6 to 12 hours, and gradually decreased afterwards. Concomitantly, GTP-CHI mRNA levels were significantly increased in liver, lungs and kidneys at 0.5 to 2 hours after endotoxin challenge （P 〈 0.05 or 0.01）, and kept high values up to 48 hours （P 〈 0.05）. Treatment with DAHP, an inhibitor of tetrahydrobiopterln synthesis, significantly reduced tissue biopterin contents at 2 to 24 hours in rats after lipopolysaccharide challenge （P 〈 0.05 or 0.01 ）. Hepatic and renal GTP-CHI mRNA expressions in the DAHP treatment group were markedly down-regulated compared with the endotoxic shock group at various intervals （ P 〈 0.05 or 0.01）, and tended to approach normal range at 12 hours in lungs. Additionally, organ functional indexes including serum ALT, AST, BUN, Cr levels and pulmonary myeloperoxidase activity were significantly decreased in the DAHP-treated group compared to the endotoxic

关 键 词：内毒素休克 生物喋呤 多器官功能障碍综合征 抑制剂 

分 类 号：R459.7[医药卫生—急诊医学]