GTPCH不是失血性休克诱导的肝脏一氧化氮生物合成的限速因素。

GTPCH is not a rate-limiting factor for hemorrhagic shock-induced hepatic nitric oxide biosynthesis.

作者信息

Cheng Ching-Rong, Huang Chun-Jen, Lu Yen-Ta, Hsu Yung-Wei, Tsai Peishan, Su Nuan-Yen, Skimming Jeffrey W

机构信息

Department of Anesthesiology, Mackay Memorial Hospital, Mackay Junior College of Nursing, Taipei, Taiwan. R.O.C.

出版信息

Acta Anaesthesiol Sin. 2002 Sep;40(3):109-16.

PMID:12434606

Abstract

BACKGROUND

Hemorrhagic shock upregulates inducible nitric oxide (NO) synthase (iNOS) expression and the resultant NO overproduction. Liver is one of the major organs that is responsible for increased NO production after trauma-hemorrhage and resuscitation. Guanosine triphosphate cyclohydrolase I (GTPCH) is the rate-limiting enzyme for the synthesis of tetrahydrobiopterin (BH4), a necessary co-factor for iNOS activity. Very little is known about the effects of hemorrhagic shock on hepatic GTPCH expression.

METHODS

Fifteen male Sprague-Dawley rats were randomly assigned to one of three groups, i.e. a sham instrumented (Sham) group, a sustained hemorrhagic shock (HS) group, and a hemorrhagic shock with resuscitation (HS/RES) group (n = 5 in each group). Controlled hemorrhagic shock was induced and the mean arterial pressure (MAP) was kept between 40-45 mmHg for sixty minutes in both HS and HS/RES groups. Then resuscitation with infusion of shed autologous blood and normal saline was performed in HS/RES group. Microdialysis probes were put in the liver and the right atrium for collection of serial samples. NO concentrations in dialysate samples were measured using chemiluminescence. Hepatic iNOS and GTPCH mRNA concentrations were analyzed using semiquantitative reverse transcription and polymerase chain reaction (RT-PCR).

RESULTS

Hemorrhagic shock induced both the hepatic and circulating NO biosynthesis as well as hepatic iNOS mRNA expression. Resuscitation with shed blood/normal saline normalized this upregulation. However, no difference was found in mean hepatic GTPCH mRNA concentrations between groups in this experiment.

CONCLUSIONS

We provide the evidence that hemorrhagic shock-induced NO biosynthesis involves upregulation of iNOS transcription in liver tissue and GTPCH transcription is unaffected by either hemorrhagic shock or resuscitation. Furthermore, microdialysis is an ideal technique for serial sampling and that events can be followed.

摘要

背景

失血性休克上调诱导型一氧化氮（NO）合酶（iNOS）的表达并导致NO过量产生。肝脏是创伤性出血和复苏后NO产生增加的主要器官之一。鸟苷三磷酸环化水解酶I（GTPCH）是四氢生物蝶呤（BH4）合成的限速酶，而BH4是iNOS活性所必需的辅助因子。关于失血性休克对肝脏GTPCH表达的影响知之甚少。

方法

15只雄性Sprague-Dawley大鼠被随机分为三组之一，即假手术组（Sham）、持续性失血性休克组（HS）和失血性休克复苏组（HS/RES）（每组n = 5）。诱导控制性失血性休克，HS组和HS/RES组的平均动脉压（MAP）在40 - 45 mmHg之间维持60分钟。然后HS/RES组输注自体失血和生理盐水进行复苏。将微透析探针置于肝脏和右心房以收集系列样本。使用化学发光法测量透析液样本中的NO浓度。采用半定量逆转录聚合酶链反应（RT-PCR）分析肝脏iNOS和GTPCH mRNA浓度。