淤血预处理减轻兔肝门静脉阻断模型中肠道淤血-再灌注损伤

Congestion preconditioning attenuate intestinal congestion-reperfusion injury in rabbit model of hepatic portal vein occlusion

目的观察淤血预处理对兔肝门静脉阻断模型中肠道淤血-再灌注引起的肠道损伤和肝脏损伤的影响。方法选取雄性日本大耳兔75只,体重2.5~5.0 kg,随机分为五组:假手术组(S组)、淤血-再灌注组(OC组)、预处理A组(OC5组)、预处理B组(OC10组)、预处理C组(OC15组),每组15只。S组仅行剖腹手术暴露第一肝门30 min,OC组进行门静脉阻断30 min后开放门静脉。三个预处理组门静脉操作分别为OC5组夹闭5 min,开放5 min;OC10组夹闭10 min,开放10 min;OC15组夹闭15 min,开放15 min,随后阻断门静脉30 min后开放。术后2、8、24 h通过门静脉取血,检测血清中丙二醛(MDA)含量和内毒素、肿瘤坏死因子-α(TNF-α)、丙氨酸转氨酶(ALT)浓度。术后24 h血液样本采集完毕后,再次麻醉并处死以获取回肠末端肠黏膜及肝组织,显微镜下观察病理形态学结构改变。结果与S组比较,术后2、8、24 h OC组、OC5组、OC10组和OC15组血清MDA含量、内毒素、TNF-α、ALT浓度明显升高(P<0.05)。与OC组比较,术后2、8、24 h OC5组、OC10组和OC15组血清MDA含量、内毒素、TNF-α、ALT浓度明显降低(P<0.05)。与OC5组比较,术后2、8、24 h OC10组血清MDA含量、TNF-α、ALT浓度明显降低(P<0.05)。与OC5组比较,术后2、8 h OC10组血清内毒素浓度明显降低(P<0.05)。与OC10组比较,术后8 h OC15组血清MDA含量、ALT浓度明显升高(P<0.05)。与S组比较,OC组、OC5组、OC10组和OC15组肠黏膜损伤Chiu评分明显升高(P<0.05)。与OC组比较,OC5组、OC10组和OC15组黏膜损伤Chiu评分明显降低(P<0.05)。与OC5组比较,OC10组、OC15组的肠黏膜损伤Chiu评分明显降低(P<0.05)。结论淤血预处理可以减轻由于肝门静脉阻断导致的肠道淤血-再灌注损伤,减轻内毒素血症、过度炎性反应及氧自由基对肝脏的损伤。

Objective To investigate the effects of congestion preconditioning on intestinal and liver injury caused by intestinal congestion-reperfusion in rabbit model of hepatic portal vein occlusion.Methods Seventy-five male Japanese big-eared rabbits were selected,weighing 2.5-5.0 kg,were divided into five groups with 15 rabbits in each group:sham operation group(group S),congestion-reperfusion group(group OC),preconditioning group A(group OC5),preconditioning group B(group OC10)and preconditioning C group(group OC15).Group S only underwent laparotomy to expose the first porta hepatis for 30 min.In group OC,portal vein was opened after portal vein occluded 30 min.Preconditioning groups were divided into group OC5(clamping 5 min and open 5 min),group OC10(clamping 10 min and open 10 min),and group OC15(clamping 15 min and open 15 min)according to different portal vein occlusion time,then portal vein was occluded for 30 min and then opened.The serum concentrations of malondialdehyde(MDA),endotoxin,tumor necrosis factor-α(TNF-α),and alanine aminotransferase(ALT)were detected in portal vein 2,8,24 h after operation.The blood sample were collected 24 h after operation,the rabbits were anesthetized again and sacrificed to obtained the intestinal mucosa of terminal ileum and liver tissue,and the pathological morphological change was observed under the microscope.Results Compared with group S,the serum concentrations of MDA,endotoxin,TNF-α,and ALT in groups OC,OC5,OC10,and OC15 were increased significantly 2,8,and 24 h after surgery(P<0.05),respectively.Compared with group OC,the serum concentrations of MDA,endotoxin,TNF-α,and ALT in groups OC5,OC10,and OC15 were significantly reduced 2,8,and 24 h after operation,respectively(P<0.05).Compared with group OC5,the serum concentrations of MDA,TNF-α,and ALT in group OC10 were significantly reduced 2,8,and 24 h after surgery(P<0.05).Compared with group OC5,the serum concentrations of endotoxin in group OC10 decreased significantly 2 and 8 h after operation(P<0.05).Compared with group OC10,the serum concentrations of MDA and ALT in group OC15 were significantly increased 8 h after operation(P<0.05).Compared with group S,the Chiu score of intestinal mucosal injury in groups OC,OC5,OC10,and OC15 was significantly increased,respectively(P<0.05).Compared with group OC,the Chiu score of mucosal injury in groups OC5,OC10 and OC15 were significantly reduced(P<0.05).Compared with group OC5,the Chiu score of intestinal mucosal injury in groups OC10 and OC15 were significantly reduced(P<0.05).Conclusion Congestion preconditioning can reduce intestinal congestion-reperfusion injury caused by hepatic portal vein occlusion,reduce endotoxemia and liver injury caused by excessive inflammatory reaction and reactive oxygen species.