摘要
目的探讨重组促红细胞生成素(rHuEPO)对脂肪肝缺血再灌注损伤(HIRI)大鼠细胞凋亡和炎症因子的影响。方法高脂饲料饲养的无特定病原体(SPF)雄性SD大鼠90只,造模成功后,采用随机数表法分为假手术组、模型组和rHuEPO组,每组30只,rHuEPO组于缺血前24 h时腹腔注射rHuEPO 4000 IU/kg,假手术组和模型组腹腔注射等容量的生理盐水,再灌注后1 h、3 h和6 h的采集血液及肝组织标本,比较各组大鼠肝细胞凋亡指数、血浆肿瘤坏死因子-α(TNF-α)和白细胞介素-1(IL-1)、血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)、肝组织丙二醛(MDA)和超氧化物歧化酶(SOD)水平。结果病理观察显示:HIRI后模型组、rHuEPO组大鼠肝组织结构改变,其中模型组改变更为明显;假手术组、模型组和rHuEPO组大鼠再灌注1 h的细胞凋亡指数分别为(3.28±0.63)%、(27.86±2.87)%、(21.38±2.62)%,差异有统计学意义(P<0.05);三组大鼠再灌注3 h的细胞凋亡指数分别为(3.56±0.83)%、(37.24±3.65)%、(28.65±2.74)%,再灌注6 h的细胞凋亡指数分别为(3.41±0.72)%、(46.92±3.88)%、(32.44±3.07)%,差异均有统计学意义(P<0.05);假手术组大鼠血清ALT及AST水平、血浆TNF-α及IL-1水平、肝组织MDA水平明显低于rHuEPO组和模型组,r HuEPO组明显低于模型组,差异均有统计学意义(P<0.05);模型组和rHuEPO组大鼠血清ALT及AST水平、血浆TNF-α及IL-1水平、肝组织MDA水平再灌注3 h组明显高于再灌注1 h组,再灌注6 h组高于再灌注3 h组,差异均有统计学意义(P<0.05);假手术组大鼠肝组织SOD再灌注1 h、3 h、6 h水平分别为(113.28±9.67)U/mg、(115.07±9.72)U/mg、(114.36±9.52)U/mg,模型组分别为(51.25±6.34)U/mg、(42.36±6.14)U/mg、(36.18±5.92)U/mg,rHuEPO组分别为(82.58±7.42)U/mg、(70.06±6.95)U/mg、(67.43±6.71)U/mg,假手术组水平明显高于rHuEPO组和模型组,rHuEPO组明显高于模型组,差异均有统计学意义(P<0.05);假手术组的不同亚组各观察指标比较,差异均无统计学意义(P>0.05)。结论r HuEPO预处理对脂肪肝大鼠再灌注后损伤具有保护作用,可有效抑制肝细胞凋亡、炎症反应及氧化应激,有效保护肝功能。
Objective To explore the influence of recombinant human erythropoietin(rHuEPO)on fatty liver apoptosis and inflammatory factors in rats with hepatic ischemia-reperfusion injury(HIRI).Methods The 90 SD male rats of specific pathogen free(SPF)were fed with high fat diet,and the rats were divided into the sham operation group,model group and rHuEPO group by random number table method,with 30 rats in each group.In rHuEPO group,rHuEPO 4000 IU/kg was injected intraperitoneally at 24 h before ischemia,and sham operated group and model group were injected with equal volume of normal saline intraperitoneally,the blood and liver tissue samples of 1 h,3 h and 6 h after reperfusion were collected.The liver cell apoptosis index,plasma tumor necrosis factor-α(TNF-α)and interleukin-1(IL-1),serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST),malondialdehyde(MDA)and superoxide dismutase(SOD)level of the three groups were compared.Results Pathological observation showed that after HIRI,the liver tissue structure of the model group and r HuEPO group were changed,and the change of model group was more obvious.After 1 h reperfusion,the apoptosis index of the sham operation group,model group and rHuEPO group were(3.28±0.63)%,(27.86±2.87)%,(21.38±2.62)%,respectively,and there were significant differences among the three groups(all P<0.05);After 3 h reperfusion,the apoptosis index of the sham operation group,model group and rHuEPO group were(3.56±0.83)%,(37.24±3.65)%,(28.65±2.74)%,respectively,and there were significant differences among of the three groups(all P<0.05);After 6 h reperfusion,the apoptosis index of the sham operation group,model group and rHuEPO group were(3.41±0.72)%,(46.92±3.88)%,(32.44±3.07)%,respectively,and there were significant differences among the three groups(all P<0.05).Serum ALT and AST levels,plasma TNF-αand IL-1,MDA levels of liver tissue of the sham operation group were significantly lower than those of r Hu EPO group and model group,and those in r Hu EPO group were also significantly lower than those of model group,the differences were statistically significant(all P<0.05);serum ALT and AST levels,plasma TNF-αand IL-1,MDA levels of the model group and r Hu EPO group after 3 h reperfusion were significantly higher than those after 1 h reperfusion,and those of the two groups after6 h reperfusion were significantly higher than those after 3 h reperfusion,all with statistically significant differences(all P<0.05);after 1 h,3 h and 6 h reperfusion,the level of SOD in liver tissue of sham operation group were(113.28±9.67)U/mg,(115.07±9.72)U/mg,(114.36±9.52)U/mg,respectively,which were significantly higher than corresponding(51.25±6.34)U/mg,(42.36±6.14)U/mg,(36.18±5.92)U/mg in model group,while those in the model group significantly higher than corresponding(82.58±7.42)U/mg,(70.06±6.95)U/mg,(67.43±6.71)U/mg in the r Hu EPO group(P<0.05).There were no significant differences in the observation indexes between the different subgroups of the sham operation group(P>0.05).Conclusion r Hu EPO preconditioning can protect hepatocytes from ischemia-reperfusion injury,inflammatory reaction and oxidative stress,and protect liver function effectively after reperfusion injury in rats with fatty liver.
作者
常顺伍
韩晓玉
宫晓光
王葆春
CHANG Shun-wu;HAN Xiao-yu;GONG Xiao-guang;WANG Bao-chun(Department of General Surgery,Hainan General Hospital,Haikou 570311,Hainan,CHINA)
出处
《海南医学》
CAS
2020年第14期1769-1773,共5页
Hainan Medical Journal
基金
海南省自然科学基金(编号:20158353)。
关键词
重组促红细胞生成素
缺血再灌注损伤
脂肪肝
大鼠
细胞凋亡
炎症因子
Recombinant human erythropoietin(rHuEPO)
Hepatic ischemia reperfusion injury(HIRI)
Fatty liver
Rats
Apoptosis
Inflammatory factors
