摘要
Objective;GTP-cyclohydrolase I (GTP-CHI) is the first and rate-limiting enzyme for the de novo bio-synthesis of biopterin.The present study was to observe the effect of 2,4-diamino-6-hydroxy-pyrimidine (DAHP),an inbibtor of GTP-CHI,on the development of postburn Staphylococcus aureus sepsis.Methods;56 male Wistarrats were randomly divided into four groups as follows;normal control group (n=10),scald control group(n=10),postburn sepsis group (n=20) and DAHP treatment group (n=16).In the scald control gro...
Objective;GTP-cyclohydrolase I (GTP-CHI) is the first and rate-limiting enzyme for the de novo bio- synthesis of biopterin.The present study was to observe the effect of 2,4-diamino-6-hydroxy-pyrimidine (DAHP), an inbibtor of GTP-CHI,on the development of postburn Staphylococcus aureus sepsis.Methods;56 male Wistar rats were randomly divided into four groups as follows;normal control group (n=10),scald control group(n=10), postburn sepsis group (n=20) and DAHP treatment group (n=16).In the scald control group,rats were subjected to a 20% total body surface area (TBSA) Ⅲ°scald injury,then sacrificed at 24 hrs.In the postburn sepsis group (n =20),rats were inflicted with 20% TBSA Ⅲ°scald followed by Staphylococcus aureus challenge,and they were further divided into 2 and 6 hrs groups.In the DAHP treatment group (n=16),animals were intraperitoneally in- jected with a dose of 1g/kg DAHP prior to Staphylococcus aureus challenge,and then further divided into 2,6 hrs groups.Tissue samples from liver,kidneys,lungs and heart were collected to determine GTP-CHI,inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α(TNF-α) mRNA expression.Meanwhile,biopterin and nitric oxide (NO) levels in these tissues were also measured.Results;After the scald injury followed by Staphylococcus aureus challenge,GTP-CHI mRNA expression and biopterin levels significantly elevated in various tissues such as liver,heart,kidneys and lungs,so did the values of iNOS mRNA expression and NO formation (P<0.01).Pre- treatment with DAHP could significantly reduce GTP-CHI/biopterin induction (P<0.05～0.01),and the up-regu- lation of iNOS/NO was also suppressed.Furthermore,DAHP administration could also inhibit the gene expression of TNF-α.2 hrs after septic challenge,TNF-α mRNA expression in liver,kidneys and lungs in DAHP-treated group were 35.7%,37.3% and 33.0% of those in postburn septic group,respectively.Additionally,in animals without DAHP treatment,the 6-hour mortality was 55.6%(20/36),while it was only 25.0% in DAHP-treated animals (4/16,P=0.08).Conclusions;Early treatment with DAHP might be a potential strategy to prevent the de- velopment of postburn Staphylococcal sepsis,which appears to be associated with down-regulation of biopterin and NO formation by DAHP.
出处
《感染．炎症．修复》
2002年第1期8-16,共9页
Infection Inflammation Repair
