CAJ | 학술논문

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 5000U/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.
목적 탐토중조인촉홍세포생성소(recombinant human erythropoietin,rHuEPO)대맹장결찰천공술(CLP)소치대서급성간손상적보호작용.방법 96지웅성SD대서수궤(수궤수자법)분위:가CLP조(대조조),CLP조(농독증조),rHuEPO조.채용맹장결찰천공술복제급성간손상적동물모형,rHuEPO조조모후즉각경미정맥추주rHuEPO 5000U/kg.수술후련속관찰24h,선택술후2h、6h、12h、24h위관찰점.분별재각시점수궤처사대서,채용매련면역법(ELISA법)검측혈청TNF-α、iNOS수평변화;동시검측간공능(ALT、AST);채용광경화투사전경관찰간조직형태학변화.결과 ①각시간점대서혈청중ALT、AST、TNF-α、iNOS수평적변화위농독증조급rHuEPO조상술지표명현고우대조조;rHuEPO조여농독증조상비,상술지표명현강저,차이구유통계학의의(P＜0.01).②광경급전경관찰발현,농독증시간장병이학개변위국조성간세포배사,염성세포침윤,소협간정맥충혈확장,간세포핵고축,선립체、내질망명현감소.rHuEPO조간장병이학개변교CLP조명현감경.결론 rHuEPO능구강저혈청중ALT、AST、TNF-α、iNOS수평,발휘조절염증반응진이개선간공능적작용,대감염소치급성간손상구유일정적보호작용.
Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on caecal ligation and puncture (CLP)-induced acute liver injury.Methods Ninety-six healthy male Sprague-Dawley rats weighing 250-300 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 5000 U/kg administered through caudalis vein after CLP procedure.Continuous observation was carried out until 24 h after modeling.Of each group,8 rats were sacrificed at 2 h,6 h,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-α)],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 (①)The levels of ALT,AST,TNF-a,iNOS in serum of rats in control group were lower than those in model group and rHuEPO group (P ＜0.01).The levels of TNF-α,IL-6 and iNOS in serum of rats in rHuEPO group were decreased significantly compared with model group (P ＜ 0.01).(②) The 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-a,iNOS in serum,thus modifying the inflammatory response and providing protective effects against acute liver injury in the wake of infection.