Sakaguchi T, Nakamura S, Suzuki S, Oda T, Ichiyama A, Baba S
Department of Surgery II, Hamamatsu University School of Medicine, Hamamatsu, Japan.
J Surg Res. 1999 Sep;86(1):116-22. doi: 10.1006/jsre.1999.5697.
Patients with portal hypertension can easily develop sepsis of enteric origin after suffering severe trauma and hemorrhagic shock. Platelet-activating factor (PAF) is one of the key mediators of such stress. The aim of this study was to investigate whether portal hypertension increases the vulnerability of the ileum to PAF.
Seven days after surgery, PAF (1.5 microg/kg) was intravenously injected into portal stenosis (PS) rats and sham-operated rats. The levels of tumor necrosis factor-alpha (TNF-alpha), cytokine-induced neutrophil chemoattractant (CINC), and endotoxin in portal plasma were determined. The levels of PAF receptor (PAFR), TNF-alpha, and CINC mRNA in the ileum were also investigated.
After PAF administration, PS rats showed (1) significantly higher portal plasma levels of TNF-alpha, CINC, and endotoxin; (2) higher histological damage scores in the ileum; (3) more infiltrating neutrophils in the ileum; and (4) a significantly higher mortality rate than sham-operated rats (P < 0.01). However, PAFR mRNA levels were similar in the two groups. The CINC mRNA level in the ileum of PS rats was increased from 1 to 4 h after PAF administration, while that of the sham-operated rats was transiently increased at 1 h.
Portal hypertension increases the vulnerability of the ileum to PAF. These findings suggest that conditions which causes PAF production may be dangerous in patients with portal hypertension.
门静脉高压患者在遭受严重创伤和失血性休克后易发生肠源性脓毒症。血小板活化因子(PAF)是此类应激的关键介质之一。本研究旨在探讨门静脉高压是否会增加回肠对PAF的易感性。
术后7天,将PAF(1.5微克/千克)静脉注射到门静脉狭窄(PS)大鼠和假手术大鼠体内。测定门静脉血浆中肿瘤坏死因子-α(TNF-α)、细胞因子诱导的中性粒细胞趋化因子(CINC)和内毒素的水平。还研究了回肠中PAF受体(PAFR)、TNF-α和CINC mRNA的水平。
给予PAF后,PS大鼠表现为:(1)门静脉血浆中TNF-α、CINC和内毒素水平显著升高;(2)回肠组织损伤评分更高;(3)回肠中浸润的中性粒细胞更多;(4)死亡率显著高于假手术大鼠(P<0.01)。然而,两组的PAFR mRNA水平相似。PAF给药后1至4小时,PS大鼠回肠中的CINC mRNA水平升高,而假手术大鼠的CINC mRNA水平在1小时时短暂升高。
门静脉高压增加了回肠对PAF的易感性。这些发现表明,导致PAF产生的情况在门静脉高压患者中可能是危险的。