乌司他丁联合缺血预处理对大鼠肝缺血再灌注损伤的影响

Effect of ulinastatin combined with ischemic preconditioning on hepatic ischemia-reperfusion injury in rats

目的探讨乌司他丁(UTI)预处理和缺血预处理(IPC)联合应用对大鼠肝缺血再灌注损伤的影响及可能的作用机制。方法选择雄性SD大鼠50只,随机分为5组,分别为对照(sham)组、缺血再灌注(IR)组、IPC组、UTI组、UTI联合缺血预处理(UCI)组。术后采集下腔静脉血并取肝组织标本,检测血清AST、ALT、TNFɑ,肝组织髓过氧化物酶(MPO)、NF-κB、肝组织湿干比(W/D)及光镜观察肝组织病理形态学变化。计量资料组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果所检测的血清ALT、AST、TNFα水平和肝组织MPO、NF-κB、W/D值,IR组、IPC组、UTI组、UCI组均明显高于sham组(P值均<0.05),而IPC组、UTI组、UCI组均明显低于IR组(P值均<0.05),UTI组明显低于IPC组(P值均<0.05),UCI组明显低于IPC组、UTI组(P值均<0.05)。肝脏病理学检查示IR组、IPC组、UTI组、UCI组与sham组比较,肝组织损伤明显(P值均<0.05),而IPC组、UTI组、UCI组均比IR组肝组织损伤程度轻(P值均<0.05),UTI组肝组织损伤轻于IPC组(P值均<0.05),UCI组肝组织损伤轻于IPC组、UTI组(P值均<0.05)。结论 UTI和UCI对肝脏缺血再灌注损伤均有保护作用,二者联合应用时,明显增强了对肝脏缺血再灌注损伤的保护效应。其发生机制可能与抑制了NF-κB表达,减少TNFɑ、MPO的释放,减轻了肝脏的炎症反应有关。

Objective To investigate the effect of ulinastatin（UTI） preconditioning combined with ischemic preconditioning（IPC） on hepatic ischemia-reperfusion（IR） injury in rats and possible mechanism of action.Methods A total of 50 male Sprague-Dawley rats were randomly divided into sham-operation group,IR group,IPC group,UTI group,and UTI-IPC group（UCI group）.Blood samples were collected from the inferior vena cava after surgery and liver tissue samples were also collected.The serum levels of aspartate aminotransferase（AST）,alanine aminotransferase（ALT）,and tumor necrosis factor-α（TNF-α）,the levels of myeloperoxidase（MPO） and nuclear factor-kappa B（NF-κB） in the liver tissue,and wet/dry weight ratio were determined,and pathomorphological changes of the liver tissue were observed under a light microscope.A one-way analysis of variance was used for comparison of continuous data between groups,and the LSD-t-test was used for further comparison between two groups.Results The IR,IPC,UTI,and UCI groups had significantly higher serum levels of ALT,AST,and TNF-α,levels of MPO and NF-κB in the liver tissue,and wet/dry weight ratio than the sham-operation group（all P〈0.05）; the IPC,UTI,and UCI groups had significantly lower levels than the IR group（all P〈0.05）,the UTI group had significantly lower levels than the IPC group（all P〈0.05）,and the UCI group had significantly lower levels than the IPC and UTI groups（all P〈0.05）.Liver pathological examination showed that compared with the sham-operation group,the IR,IPC,UTI,and UCI groups had significantly greater liver injury（all P〈0.05）,while the IPC,UTI,and UCI groups had a significantly lower degree of liver injury than the IR group（all P〈0.05）,the UTI group had significantly slighter liver injury than the IPC group（P〈0.05）,and the UCI group had significantly slighter liver injury than the IPC and UTI groups（both P〈0.05）.Conclusion Both UTI and UCI have a protective effect against hepatic IR injury,and the combination of UTI and UCI significantly enhances such protective effect,possibly by inhibiting the expression of NF-κB,reducing the release of TNF-α and MPO,and alleviating liver inflammatory response.