Multiple organ inflammatory response to portosystemic shunt in the rat

Multiple organ inflammatory response to portosystemic shunt in the rat
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DOI:
10.1016/j.cyto.2011.08.033
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发表时间:
2011-12-01
期刊:
影响因子:
3.8
通讯作者:
Arias, Jaime
Arias, Jaime
中科院分区:
医学3区
文献类型:
--
作者:
Garcia, Cruz;Gine, Elena;Arias, Jaime

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门体分流术是预防食道静脉曲张再出血的最佳方法,但术后炎性并发症的风险很高,包括肝性脑病。因此,门体分流手术可引起全身炎症反应,并伴有包括肝性脑病在内的多器官功能障碍综合征。为了验证这一假设,我们使用了术后6周的雄性Wistar大鼠:对照组(CR;n=14)、假手术组(SO;n=8)和门腔静脉端侧分流术的大鼠(PCS;n=15)。用ELISA法检测肿瘤坏死因子-α、IL-1β和IL-10的表达,用Western-印迹法检测血管内皮细胞的内皮型一氧化氮合酶(ENOS)、诱导型一氧化氮合酶(INOS)、构成型和诱导型血红素加氧酶(HO-1和HO-2)的表达。逆转录聚合酶链式反应(RT-PCR)法检测小肠、肝、脾、肺组织中HO-1、HO-2、TNF-α、IL-1β和IL-10的表达水平。在大鼠的门腔分流术中,会导致促炎和抗炎介质的器官间失衡。肝脏组织中肿瘤坏死因子-αmRNA表达降低(0.69+/-0.28,p<0.05)。肝脏产生IL-1β(204.13+/-71.90pg/100g;p<0.001)和IL-10(4505.47+/-337.97 pg/100g;p<0.001)也减少。而肠道促炎症(肿瘤坏死因子-α:1471.86+/-153.62 pg/100g,p<0.001;IL-1β:48.35+/-9.84pg/100g,p<0.001和诱导型一氧化氮合酶:0.59+/-0.001,p<0.01)和抗炎(IL-10:1503.39+/-53.5pg/100g,p<0.001和HO-1:2.23+/-0.001,p<0.001)增加调解员。在大鼠的全门腔分流术中,内脏-肺轴上的促炎和抗炎介质的损伤可能与多器官功能障碍综合征有关。因此,门体分流术后的并发症可以整合为可能源于肠道的全身炎症反应。(C)2011爱思唯尔有限公司。保留所有权利。
Portosystemic shunt surgery is the best procedure to prevent recurrent bleeding of esophageal varices, but carries a high risk of postoperative inflammatory complications, including hepatic encephalopathy. Thus, portosystemic shunting procedures could induce a systemic inflammatory response with multiple organ dysfunction syndrome, including hepatic encephalopathy. To verify this hypothesis we used male Wistar rats at 6 weeks of postoperative evolution: Control (CR; n = 14), Sham-operated (SO; n = 8) and rats with end-to-side portacaval shunt (PCS; n = 15). TNF-alpha, IL-1 beta and IL-10 were assayed by ELISA techniques, the expression of the endothelial constitutive nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), constitutive and inducible heme-oxygenase (HO-1 and HO-2) were assayed by Western-blot. mRNA levels of HO-1, HO-2, TNF-alpha, IL-1 beta and IL-10 were quantified by reverse transcriptase polymerase chain reaction amplification (RT-PCR) in the small bowel, liver, spleen and lungs. Portacaval shunting in the rat produces an interorgan imbalance of pro- and anti-inflammatory mediators. TNF-alpha mRNA expression is decreased in the liver (0.69 +/- 0.28, p < 0.05). The hepatic production of IL-1 beta (204.13 +/- 71.90 pg/100 g; p < 0.001) and IL-10 (4505.47 +/- 337.97 pg/100 g; p < 0.001) is also decreased. However, the intestinal pro-inflammatory (TNF-alpha: 1471.86 +/- 153.62 pg/100 g, p < 0.001; IL-1 beta: 48.35 +/- 9.84 pg/100 g, p < 0.001 and iNOS: 0.59 +/- 0.01, p < 0.01) and anti-inflammatory (IL-10: 1503.39 +/- 53.5 pg/100 g, p < 0.001 and HO-1: 2.23 +/- 0.16, p < 0.001) mediators are increased. Total portacaval shunting in the rat induces impairments of pro- and anti-inflammatory mediators in the splanchnic-lung axis that could be associated with a multiple organ dysfunction syndrome. Therefore, the complications after portosystemic shunts could be integrated into a systemic inflammatory response of possible intestinal origin. (C) 2011 Elsevier Ltd. All rights reserved.