右美托咪啶预处理对大鼠自体原位肝移植术后肠道损伤的影响

Effects of Dexmedetomidine Preconditioning on Gut Injury after Orthotopic Autologous Liver Transplantation in Rats

【目的】建立大鼠自体原位肝移植模型,探讨右美托咪啶(Dex)及其拮抗剂阿替美唑(Atip)预处理对大鼠自体原位肝移植术后肠道结构与功能改变的影响。【方法】48只成年SD大鼠,随机分为假手术组(S组)、模型组(M组)、低剂量Dex预处理组(D1组),高剂量Dex预处理组(D2组),低剂量Atip+低剂量Dex预处理组(A1组),高剂量Atip+高剂量Dex预处理组(A2组)。术后8 h留取末端回肠与动脉血,观察肠黏膜病理改变并行Chiu’s评分,ELISA法检测血清内毒素(LPS)水平与二胺氧化酶(DAO)活性,分光光度法测定肠道MDA含量与SOD活力,Western blotting法检测肠上皮紧密连接Occludin与ZO-1蛋白的表达。【结果】M组肠道病理损伤严重,LPS与MDA水平升高,紧密连接破坏;Dex预处理后,D2组较D1组肠道保护效应明显,LPS与MDA水平降低,SOD活力增强;相反,Atip+Dex预处理后,Dex肠道保护效应显著减弱。【结论】Dex预处理呈剂量依赖性地减轻大鼠自体原位肝移植术后的肠道损伤,可能与其抗炎、抗氧化作用密切相关。

[Objective] To establish a rat model of orthotopic autologous liver transplantation （OALT）,and to investigate the effects of dexmedetomidine （Dex） and atipamezole （Atip） preconditioning on the changes of intestinal structure and function after OALT in rats.[Methods] Forty-eight adult Sprague-Dawley rats were randomly assigned into Sham group （group S）,Model group （group M）,low dosage Dex group （group D1）,high dosage Dex group （group D2）,low dosage Atip＋ low dosage Dex group （group A1）,high dosage Atip＋ high dosage Dex group （group A2）.Rats were sacrificed 8 h after the operation,and terminal ileum was harvested as to evaluate the intestinal mucosa histopathology.The level of serum lipopolysaccharide （LPS） and diamineoxidase （DAO） was tested by ELISA.Spectrophotometry assay for MDA and SOD,as well as Western-blotting for Occludin and ZO-1 expression on intestinal epithelium,was performed.[Results] The intestinal mucosa injury,and high level of LPS and MDA were clearly observed in group M.With Dex pretreatment,the gut injury was obviously attenuated,and Dex exerted anti-inflammatory and anti-oxidant effect,particularly in D2 group.Meanwhile,with Atip＋Dex pretreatment,the beneficial effect of Dex was completely reversed.[Conclusion] Dex provided dose-dependent gut-protection for intestinal injury after OALT in rats.The anti-inflammatory and anti-oxidant effect of Dex,may majorly contributed to its gut-protective effect.