乌司他丁对失血性休克大鼠肝脏缺血再灌注损伤保护作用的研究

Effect of ulinastatin on prevention of ischemia/reperfusion liver injury during hemorrhagic shock and reperfusion in rats

目的:探讨乌司他丁对失血性休克大鼠肝脏缺血再灌注损伤的保护作用及机制。方法:24只雄性Wista大鼠随机分为假手术组、生理盐水治疗组、乌司他丁治疗组,每组8只。建立大鼠失血性休克模型。乌司他丁治疗组,予以乌司他丁25000U·kg-1加入2mL生理盐水静脉推注,并完成液体复苏;生理盐水治疗组予以2mL生理盐水静脉推注,并完成复苏;假手术组,除不放血和输液外,其他处理与模型相同。观察3h后处死大鼠,取血液离心分离血浆检测肝功能指标、血清肿瘤坏死因子(TNF-α);取肝右叶2块肝组织,1块用于肝组织病理改变和肝细胞凋亡观察;1块用于肝组织匀浆,离心取上清液进行肝组织MDA、SOD、髓过氧化物酶(MPO)检测。结果:失血性休克大鼠肝脏再灌注3h后,生理盐水治疗组肝组织发生了严重缺血再灌注损伤,肝细胞水样变,肝窦淤血变窄,间质大量炎性细胞浸润,而乌司他丁治疗组仅有轻度再灌注损伤。乌司他丁治疗组肝细胞凋亡、肝功能指标ALT、AST、血清TNF-α水平、肝组织MDA含量、MPO活性较生理盐水治疗组均有不同程度的减少(P<0.05),SOD活性较生理盐水治疗组升高(P<0.05)。结论:乌司他丁对大鼠失血性休克再灌注后肝脏损伤具有保护作用,其机制可能与抑制中性粒细胞浸润、抑制氧自由基的形成、抗肝细胞凋亡相关。

Objective： To investigate the protective effect of ulinastatin on the prevention of ischemia/reperfusion liver injury during hemorrhagic shock and reperfusion in rats.Methods： The model of hemorrhagic shock in rats was produced by Chaudry method.24 male Wistar rats, weighting 210 g to 250 g, were randomly divided into 3 groups：sham operation group,normal saline-treated group in which the rats were resuscitated by transfusion of shed blood and normal saline, ulinastatin-treated group in which the rats were treated with ulinastatin. The rats were sacrificed at 3h after reperfusion, and liver tissues and blood samples were collected. The liver tissues morphological changes were examined, and the contents of alanine aminotransferase（ALT）, aspartate aminol transferase（AST）, tunlornecrosisfactor-α（TNF-α）in serum, and the malondialdehyde（MDA）, superoxidase dismutase（SOD）, myeloperoxidase（MPO）in liver were also determined.Results： Compared with ulinastation group,the liver tissues in the normal saline-treated group showed obvious pathological changes , and serious reperfusion liver injurys occured. Apoptotic index of hepatic cells, ALT, AST, TNF-α, MDA and MPO contents were significantly lower,SOD contents were significantly higher in ulinastatin group than those in normal saline-treated group （all P0.05）.Conclusion： Ulinastatin has protective effect on liver against reperfusion injury.It＇s mechanism is related to inhibition of anti-oxidation, anti-apoptosis, and aggregation neutrophil＇s accumulation effect of ulinastatin.