抑制生物蝶呤合成对大鼠烫伤后金葡菌感染所致肺损伤的影响

为探讨生物蝶呤 (BH4 )在金黄色葡萄球菌 (简称金葡菌 )脓毒症所致急性肺损伤中的作用及BH4 合成抑制剂的防护效应 ,将 5 6只动物随机分为正常对照组、烫伤对照组、烫伤后金葡菌感染组和 2 ,4 二胺 6 羟基嘧啶 (DAHP)拮抗组。分别检测肺组织三磷酸鸟苷环水解酶I(GTP CHI)、诱生型一氧化氮合酶 (iNOS)基因表达 ,以及BH4 和一氧化氮 (NO)等介质的含量。结果显示 ,早期给予生物蝶呤合成限速酶抑制剂 (DAHP不仅可显著抑制组织GTP CHI基因表达和BH4 的产生 ,iNOS基因表达和NO生成亦明显受抑 (P <0 .0 5 )。同时 ,注射DAHP可在一定程度上减少肺组织肿瘤坏死因子 α的产生 (P <0 .0 5 ) ,肺组织髓过氧化物酶活性也有所下降。本结果表明 ,严重烫伤后金葡菌感染所致BH4 大量产生可能是介导急性肺损伤的重要原因之一 ,感染早期及时抑制BH4 的合成可能有助于金葡菌脓毒症的防治

THE EFFECT OF BIOPTERIN SYNTHESIS INHIBITOR ON ACUTE LUNG INJURY IN POSTBURN STAPHYLOCOCCUS AUREUS SEPSIS

To determine the role of biopterin in acute lung injury in scald rats with infection, and to observe the therapeutic effect of GTP-cyclohydrolase I(GTP-CHI) inhibitor on postburn sepsis, 56 male Wistar rats were randomly divided into four groups: normal controls (n=10), scald control group(n=10), postburn sepsis group(n=20) and 2,4-diamino-6-hydroxy-pyrimidine (DAHP) treatment group (n=16). Tissue samples from lungs were collected to determine GTP-CHI and inducible nitric oxide synthase (iNOS) mRNA expression, meanwhile biopterin, nitric oxide (NO), tumor necrosis factor-α(TNF-α) and interferon-γ (IFN-γ) levels in lungs were also measured. The results showed that after scald injury followed by Staphylococcus aureus challenge, GTP-CHI gene expression and biopterin levels significantly elevated in lungs, so did the values of iNOS mRNA expression and NO induction (P<0.05～0.01). Pulmonary myeloperoxidase (MPO) activities were also increased. Early treatment with DAHP could significantly reduce GTP-CHI/biopterin induction as well as iNOS/NO levels and MPO activities. The levels of TNF-α and INF-γ both in tissue and plasma were also decreased to certain extent. These results suggest that excessive production of biopterin may play an important role in the patho-genesis of acute lung injury after severe burns combined with Staphylococcus aureus challenge, and early treatment with biopterin synthesis inhibtor might be a potential strategy to prevent the development of sepsis.