过氧化物酶体增殖物激活受体-γ激动剂罗格列酮对肝门阻断所致肠道损伤的保护作用及机制

Protective effect of peroxisome proliferators-activated receptor-γ agonist rosiglitazone against the intestinal injury induced by hepatic inflow occlusion

目的 探讨过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂罗格列酮在肝门阻断所致肠道损伤中的作用和机制.方法 将雄性SD大鼠随机分为4组：对照组（CTL）、假手术组（Sham）、肝门阻断组（HIO）和罗格列酮预处理组（Ros）.采用Pringle＇s法行肝门阻断,持续30 min.解除阻断血流恢复2h后,测定回肠组织丙二醛（MDA）、超氧化物歧化酶（SOD）的含量,检测血清二胺氧化酶（DAO）、白细胞介素-1β（IL-1β）以及肿瘤坏死因子·α（TNF-0）的水平.结果 相对于HIO组,Ros组大鼠回肠组织MDA含量降低[（1.91 ±0.40） nmol/mg蛋白比（4.71 ±0.72） nmol/mg蛋白,P＜0.01],SOD活性升高[（217.48±37.30） U/mg蛋白比（151.13 ±30.59） U/mg蛋白,P＜0.01],血清DAO[（16.02 ±2.04） U/L比（20.83±2.46） U/L,P＜0.01]、IL-1β[（121.11±24.34） ng/L比（309.10±37.39） ng/L,P＜0.05]及TNF-t[（26.35 ±7.19） ng/L比（101.95±18.68） ng/L,P＜0.05]水平均显著下降.结论 PPAR-、γ激动剂罗格列酮通过减轻组织氧化应激反应、抑制促炎因子的过表达,对肝门阻断造成的肠道损伤具有保护作用.

Objective To investigate the effect of peroxisome proliferators-activated receptor-γ （PPAR-γ） agonist rosiglitazone on the intestinal injury induced by hepatic inflow occlusion （HIO）.Methods Sprague-Dawley male rats were randomly divided into four groups：control （CTL） group,sham group,HIO group and rosiglitazone pretreatment （Ros） group.Hepatoduodenal ligament was occluded （Pringle manoeuvre） by clamp for 30 min.After allowing reperfusion for 2 h by release of the clamp,ileac tissue level of malonaldehyde （MDA）,activity of superoxide dismutase （SOD） and serum content of diamine oxidase （DAO） were assessed according to the corresponding kits.Serum levels of interleukin （IL）-1β and tumor necrosis factor （TNF）-α were detected by using enzyme-linked immunosorbent assay.Results As compared with HIO group,rosiglitazone significantly reduced the tissue level of MDA [（1.91 ±0.40）nmol/mg protein vs.（4.71 ± 0.72） nmol/mg protein,P ＜ 0.01],enhanced the activity of SOD [（217.48-37.30） U/rg protein vs.（151.13 ± 30.59） U/mg protein,P ＜ 0.01],decreased the levels of DAO [（16.02-2.04） U/L vs.（20.83±2.46） U/L,P＜0.01],IL-l[β [（121.11 ±24.34） ng/L vs.（309.10±37.39） ng/L,P＜0.05] aswellasTNF-α [（26.35 ±7.19） ng/Lvs.（101.95-18.68）ng/L,P ＜ 0.05] in serum.Conclusion PPAR-γ agonist rosiglitazone can protect against intestinal injury caused by HIO though the mechanism of attenuating oxidative stress and inhibiting the overexpression of proinflammatory cytokines.