生物喋呤在烫伤后金黄色葡萄球菌脓毒症中的变化规律及其意义

Significance of changes in biopterin synthesis and release in rats with postburn Staphylococcus aureus sepsis

目的 观察生物喋呤 (主要是四氢生物喋呤 ,BH4 )在金黄色葡萄球菌 (金葡菌 )脓毒症中的分布特点及变化规律 ,并初步探讨BH4 的生成与多器官功能损害的关系。 方法 70只Wistar大鼠随机分为正常对照组 (C组 ,10只 )、烫伤对照组 (TC组 ,10只 )和烫伤后金葡菌感染组(BF组 ,5 0只 )。TC组和BF组采用大鼠 2 0 %TBSAⅢ度烫伤模型 ,BF组在烫伤后 2 4h再用金葡菌攻击制成烫伤后脓毒症模型 ,检测各组心、肝、肺、肾组织中三磷酸鸟苷环水解酶Ⅰ (GTP -CHⅠ )mRNA的表达及组织BH4 的含量 ,同时测定上述器官功能指标的变化情况。 结果 烫伤后金葡菌感染可导致动物心、肝、肺、肾组织GTP -CHⅠ基因表达明显升高 ,伤后 2 4h仍持续于较高水平(P <0 .0 5～ 0 .0 1)。与之相应 ,肝、肺、肾组织中BH4 的产生亦显著增加。烫伤后金葡菌攻击动物血清谷丙转氨酶、谷草转氨酶、肌酐 (Cr)、心肌型肌酸激酶同工酶 (CK -MB)及肺组织髓过氧化物酶活性明显升高 (P <0 .0 5～ 0 .0 1)。相关分析显示 ,心组织GTP -CHⅠmRNA表达和肾组织BH4 含量分别与血清CK -MB和Cr水平呈显著正相关 (分别为r =0 .892 ,P =0 .0 0 12和r =0 .942 3,P =0 .0 0 15 )。 结论 烫伤后金葡菌感染可从基因水平诱导体内BH4 的从头合成 ,BH4 在介导多器?

Objective To observe the time course and tissue distribution of biopterin, a cofactor of nitric oxide synthase (NOS), in postburn Staphylococcus aureus infection, and to investigate its potential role in the pathogenesis of sepsis. Methods Wistar rats inflicted with 20% TBSA Ⅲ degrees scald followed by Staphylococcus aureus challenge, then GTP-cyclohydrolase Ⅰ (GTP-CHⅠ) mRNA expression and biopterin levels in the liver, kidney, lung and heart were determine at 0.5, 2, 6, 12, and 24 hours following Staphylococcus aureus challenge. Results After Staphylococcus aureus challenge, GTP-CHⅠ gene expression was up-regulated markedly in various tissues, and kept at high levels up to 24 hours ( P < 0.05 ～ 0.01 ). Similarly, biopterin levels in these tissues significantly elevated. Meanwhile, serum glutamic pyruvic transaminase, glutamic oxalacetic transaminase, creatinine (Cr), MB isoenzyme of creatine kinase (CK-MB) levels and pulmonary myeloperoxidase activities significantly increased at 24 hours postburn, and the multiple organ dysfunction was aggravated by Staphylococcus aureus challenge. Moreover, it was shown that cardiac GTP-CHI mRNA expression and renal BH 4 levels were positively correlated with CK-MB and Cr ( r = 0.892 , P = 0.0012 and r = 0.9423 , P = 0.0015 , respectively). Conclusions Thermal injury combined with Staphylococcus aureus challenge can induce de novo biosynthesis of biopterin, which, acting as the most important cofactor of iNOS, may play a role in the development of multiple organ dysfunction syndrome secondary to postburn sepsis.