重组人促红细胞生成素对感染致急性肝脏损伤大鼠的保护作用  

Protective effects of recombinant human erythropoietin against acute liver injury induced by sepsis in rats.

作　　者：桑珍珍[1] 许云[1] 盛英杰[1] 贾冬[1] 金帅[1] 张鹏思[1] 赵敏[1] 

机构地区：[1]中国医科大学附属盛京医院急诊科,沈阳110004

出　　处：《中华急诊医学杂志》2014年第12期1327-1332,共6页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金（81171793）;国家临床重点专科建设项目资助

摘　　要：目的探讨重组人促红细胞生成素（recombinant human erythropoietin，rHuEPO）对盲肠结扎穿孔术（CLP）所致大鼠急性肝损伤的保护作用。方法96只雄性SD大鼠随机（随机数字法）分为：假CLP组（对照组），CLP组（脓毒症组），rHuEPO组。采用盲肠结扎穿孔术复制急性肝损伤的动物模型，rHuEPO组造模后即刻经尾静脉推注rHuEPO 5OOOU／kg。手术后连续观察24h，选择术后2h、6h、12h、24h为观察点。分别在各时点随机处死大鼠，采用酶联免疫法（ELISA法）检测血清TNF-α、iNOS水平变化；同时检测肝功能（ALT、AST）；采用光镜和透射电镜观察肝组织形态学变化。结果①各时间点大鼠血清中ALT、AST、TNF-α、iNOS水平的变化为脓毒症组及rHuEPO组上述指标明显高于对照组；rHuEPO组与脓毒症组相比，上述指标明显降低，差异具有统计学意义（P〈0．01）。②光镜及电镜观察发现，脓毒症时肝脏病理学改变为局灶性肝细胞坏死，炎性细胞浸润，小叶间静脉充血扩张，肝细胞核固缩，线粒体、内质网明显减少。rHuEPO组肝脏病理学改变较CLP组明显减轻。结论rHuEPO能够降低血清中ALT、AST、TNF-α、iNOS水平，发挥调节炎症反应进而改善肝功能的作用，对感染所致急性肝损伤具有一定的保护作用。Objective To investigate the protective effects of recombinant human erythropoietin （rHuEPO） on eaecal ligation and puncture （CLP） -induced acute liver injury. Methods Ninety-six healthy male Sprague-Dawley rats weighing 25O - 3OO g were randomly divided into 3 groups ： normal control group （ sham group, n = 32） , CLP model group （ sepsis group, n = 32） and rHuEPO treatment group （ n = 32）. The rat model of sepsis was established by caecal ligation and puncture. In treatment group, rats were treated with rHuEPO 5OOO U/kg administered through caudalis vein after CLP procedure. Continuous observation was carried out until 24 b after modeling. Of each group, 8 rats were sacrificed at 2 h, 6 b, 12 h and 24 h, respectively, and then the liver tissue samples and blood samples were collected. Blood samples were assayed for determining the levels of serum cytokines [ tumor necrosis factor-alpha （ TNF-a） ], and inducible nitric oxide synthase （iNOS） by using the enzyme-linked immunoadsorbentassay （ELISA） method. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were also detected. Histopathological changes of liver tissues were observed under optical and transmission electron microscopy. Results ①The levels of ALT, AST, TNF-α, iNOS in serum of rats in control group were lower than those in model group and rHuEPO group （P 〈O. O1 ）. The levels of TNF-α, IL-6 and iNOSin serum of rats in rHuEPO group were decreased significantly compared with model group （P 〈 O.O1 ）.②The optical microscopy and the transmission electron microscopy showed hepatocyte edema, liver focal necrosis, inflammatory cell infiltration in portal area and severe congestion of interlobular veins, hepatocyte karyopyknosis, mitochondrial and endoplasmic reticulum （ER） obviously decreased in sepsis group at 24 h. Hepatic injury was attenuated after employment of rHuEPO. Conclusions Recombinant human erythropoietin can inhibit the levels of ALT, AST, TNF-α, iN

关 键 词：重组人促红细胞生成素 盲肠结扎穿孔术 脓毒症 急性肝损伤 

分 类 号：R575[医药卫生—消化系统]