门冬氨酸鸟氨酸联合奥拉米特对急性肝衰竭大鼠肝功能的影响  

Effects of ornithine aspartate combined with orazamide on liver function of acute liver failure rats

作　　者：李晶晶[1] 张文馨 张倩[1] 刘艳月[1] 谷红丽[1] 万菲菲 王晶[2] LI Jingjing;ZHANG Wenxin;ZHANG Qian;LIU Yanyue;GU Hongli;WAN Feifei;WANG Jing(Department of Infection,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052;Department of Hepatobiliary Surgery,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052)

机构地区：[1]郑州大学第一附属医院感染科,郑州450052 [2]郑州大学第一附属医院肝胆外科,郑州450052

出　　处：《郑州大学学报（医学版）》2021年第5期598-602,共5页Journal of Zhengzhou University(Medical Sciences)

基　　金：河南省高等学校重点科研项目计划(18A320061)。

摘　　要：目的:探讨门冬氨酸鸟氨酸(OA)联合奥拉米特对急性肝衰竭大鼠肝功能的影响。方法:雄性SD大鼠分5组处理。正常对照组(n=8)腹腔注射生理盐水(5 mL/kg)。余4组采用腹腔注射D-氨基半乳糖(700 mg/kg)联合脂多糖(3μg/kg)的方法建立急性肝衰竭大鼠模型,并分别于造模前24、16、8 h,以及造模后8、16 h灌胃生理盐水5 mL/kg(模型对照组)、OA 1.0 g/kg(OA组)、奥拉米特0.036 g/kg(奥拉米特组)、OA+奥拉米特(联合干预组),每组6只大鼠。最后一次灌胃24 h后检测大鼠肝功能指标、血氨及乳酸浓度;HE染色观察大鼠肝组织病理变化;免疫组化法检测肝组织中氨甲酰磷酸合成酶(CPS)Ⅰ、CPSⅡ的表达。结果:与正常对照组相比,模型对照组大鼠血氨、乳酸、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TB)、直接胆红素(DB)、血清白蛋白(ALB)浓度均升高(P<0.05);肝组织中CPSⅠ蛋白表达下降,CPSⅡ表达升高(P<0.05);肝组织病理呈弥漫性肝细胞坏死,肝窦出血,肝小叶结构紊乱,炎症细胞浸润。与模型对照组比较,OA组大鼠血氨、乳酸浓度以及肝功能指标均降低(P<0.05),联合干预组降低更明显(P<0.05);OA组及联合干预组肝组织病变减轻,奥拉米特组未见明显变化;OA组肝组织中CPSⅠ蛋白表达升高,CPSⅡ蛋白表达下降(P<0.05),联合干预组改变更明显(P<0.05)。结论:急性肝衰竭时机体血氨代谢通路改变,OA和奥拉米特联用可改善急性肝衰竭大鼠的肝功能。Aim:To investigate the effects of ornithine aspartate(OA)and orazamide on acute liver failure(ALF)rats.Methods:Male SD rats were allocated into 5 groups.The normal control group(n=8)was intraperitoneally injected with normal saline(5 mL/kg).The other four groups were injected intraperitoneally with D-galactosamine(700 mg/kg)combined with lipopolysaccharide(3μg/kg)to establish ALF model,and gavage of 5 mL/kg normal saline(model group),OA 1.0 g/kg(OA group),orazamide 0.036 g/kg(orazamide group),or OA+orazamide(combined intervention group)24,16 and 8 hours before and 8 and 16 hours after modeling was performed,respectively,and 6 rats in each group.24 hours after the last gavage,the indexes of liver function,the concentrations of blood ammonia and lactic acid were measured,the pathological changes of rat liver were observed by HE staining,the expressions of carbamoyl phosphate synthase(CPS)Ⅰand CPSⅡin liver tissue were detected by immunohistochemistry.Results:Compared with the normal control group,the concentrations of blood ammonia,lactic acid,alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TB),direct bilirubin(DB)and serum albumin(ALB)in the model group increased(P<0.05),the expression of CPSⅠprotein decreased and the expression of CPSⅡincreased(P<0.05);the liver histopathology showed diffused hepatocyte necrosis,hepatic sinus hemorrhage,disorder of hepatic lobule structure and infiltration of inflammatory cells.Compared with the model group,the concentrations of blood ammonia,lactic acid and liver function indexes in the OA group decreased(P<0.05),especially in the combined intervention group(P<0.05).The liver lesions in the OA group and the combined intervention group were less than those in the model group,and there was no significant change in the orazamide group.Compared with the model group,the expression of CPSⅠprotein increased and CPSⅡprotein decreased in the OA group(P<0.05),especially in the combined intervention group(P<0.05).Conclusion:The blood ammonia metabo

关 键 词：急性肝衰竭 门冬氨酸鸟氨酸 奥拉米特 大鼠 

分 类 号：R575.3[医药卫生—消化系统]