摘要
目的 探讨生物喋呤合成限速酶抑制剂 - 2 ,4 二胺 6 羟基嘧啶 (DAHP)对金黄色葡萄球菌 (简称金葡菌 )脓毒症的保护效应及机制。 方法 5 6只Wistar大鼠随机分为正常对照组、2 0 %TBSAⅢ度烫伤对照组、烫伤后金葡菌感染组和DAHP拮抗组。无菌留取大鼠心、肝、肺、肾组织检测三磷酸鸟苷环水解酶I(GTP CHI)、诱生型一氧化氮合酶 (iNOS)及肿瘤坏死因子α (TNFα )基因表达 ,同时测定组织中四氢生物喋呤 (BH4)和一氧化氮 (NO)的水平。 结果 烫伤后金葡菌感染可导致组织GTP CHI基因表达广泛上调、BH4合成显著增加。同时 ,组织iNOSmRNA表达和NO水平亦明显升高 ,其中肝、肺改变尤为显著。给予DAHP不仅可显著抑制各组织GTP CHImRNA表达和BH4的产生 (P<0 .0 5～ 0 .0 1) ,iNOSmRNA表达和NO的生成亦明显受抑 ,同时TNFα表达也明显降低。此外 ,DAHP拮抗组动物 6h死亡率有所降低 (分别为 2 5 .0 %和 5 5 .6 % ,P =0 .0 8)。 结论 DAHP早期干预可在一定程度上改善革兰阳性菌脓毒症动物的预后 ,其机制可能与DAHP抑制体内BH4和NO的产生有关。
Objective To investigate the protect iv e effect and its underlying mechanism of 2,4 diamino 6 hydroxy pyrimidine (D AHP), an inhibitor of GTP cyclohydrolase I (GTP CHI), on postburn Staphylococc us aureus (S. aureus) sepsis in rats. Methods Fifty six Wistar rats were randomly divided into four g roups, i.e. normal control, scalding control, postburn sepsis group and DAHP tr eatment group . Tissue samples from liver, kidneys, lungs and heart were aseptic ally taken, and in which the GTP CHI and inducible nitric oxide synthase (iNOS) contents and the mRNA expression of tumor necrosis factor α (TNFα) were dete rmined. Furthermore, biopterin (BH 4) and nitric oxide (NO) levels in these tis sue were also measured. Results After the scalding injury followed by bacterial challeng e, the GTP CHI gene expression and biopterin levels were significantly increase d in all tissue sampled, and so were iNOS mRNA expression and NO (P<0.01), e specially in liver and lungs. The expressions of GTP CHI mRNA and iNOS mRNA and the production of BH 4 and NO in all tissue were evidently inhibited by the pr etreatment with DAHP (P<0.05～0.01). At the same time, the TNFα expression w as also obviously decreased. In addition,The mortality at 6 hr in rats of DAHP t reatment group was decreased. Conclusion The prognosis of the scalding rats complicated by sep sis caused by G + bacteria could be improved by DAHP pretreatment, which might be related to the inhibition of the production of BH 4 and NO by DAHP.
出处
《中华烧伤杂志》
CAS
CSCD
2002年第2期84-87,共4页
Chinese Journal of Burns
基金
国家重点基础发展规划项目 (G19990 5 42 0 3 )
国家杰出青年科学基金 (3 0 12 5 0 2 0 )
军队杰出中青年人才专项基金(98J0 13 )
北京市"十五"重大计划研究项目
