摘要
目的了解内毒素休克时重要器官生物喋呤及其合成限速酶基因表达的改变和病理生理意义。方法采用大鼠内毒素休克模型，检测肝、肾、肠等组织生物喋呤含量、三磷酸鸟苷环水解酶Ⅰ（ＧＴＰＣＨＩ）ｍＲＮＡ表达及器官功能指标等，并观察内毒素拮抗剂———重组杀菌／通透性增加蛋白（ｒＢＰＩ２１）的防治效果。结果内毒素休克动物肝、肾、肠等组织生物喋呤含量明显增多，伤后８小时升高幅度尤为显著（Ｐ＜００５，Ｐ＜００１）；同时，不同组织ＧＴＰＣＨＩｍＲＮＡ表达亦显著增强。相关分析显示，肝、肾组织生物喋呤含量分别与谷丙转氨酶、尿素氮值呈显著正相关（Ｐ＜００１）。给予ｒＢＰＩ２１治疗可不同程度地降低组织生物喋呤及ＧＴＰＣＨＩ基因转录水平（Ｐ＜００５，Ｐ＜００１），并减轻肝、肾及肠功能损害。结论生物喋呤参与了内毒素休克所致多脏器损害发病过程，早期拮抗内毒素可抑制组织生物喋呤的合成与释放。
Objective To investigate the
potential role of changes in biopterin (tetrahydrobiopterin and more oxidized species) synthesis
and GTP cyclohydrolase I (GTPCHI) mRNA expression in endotoxic shock. Methods SD rats
were subjected to endotoxic shock by a bolus injection of lipopolysaccharide (15 mg/kg, i.p.),
biopterin and GTPCHI mRNA levels in liver, kidney, and intestine were determined at 4, 8 hours
following endotoxin challenge. ResultsTissue biopterin levels significantly elevated in liver,
kidney, and intestine, with high levels sustaining for 8 hours after endotoxin challenge
(P<005,P<001). Similarly, GTPCHI mRNA induction in various tissues substantially increased
within 4 hours compared to normal controls (P<005,P<001). It was also shown that hepatic and
renal biopterin levels were positively correlated with glutamic pyruvic transaminase (GPT) and
also blood urea nitrogen (BUN) values (both P<001). In addition, treatment with recombinant
bactericidal/permeability increasing protein (rBPI21) markedly reduced tissue biopterin and
GTPCHI mRNA levels, concomitant with significant decreases in GPT, BUN as well as Dlactate
values. ConclusionsT5BZBiopterin synthesis and release may be involved in the development
of endotoxininduced multiple organ dysfunction, and early use of rBPI21 is effective to inhibit
marked GTPCHI mRNA expression and biopterin formation following septic shock.
出处
《中华外科杂志》
CAS
CSCD
北大核心
1999年第5期267-270,共4页
Chinese Journal of Surgery
基金
国家自然科学基金
军队杰出中青年人才专项基金
奥地利科学发展促进会基金
关键词
内毒素休克
限速酶
生物喋呤
基因表达
Shock, septicMultiple organ failureBiopterinRecombinant proteinsGene expression
