极化液对内毒素血症大鼠肝损伤的影响

Effects of GIK on liver injury induced by lipopolysaccharide in rats

目的研究葡萄糖-胰岛素-钾(极化液,GIK)对内毒素血症大鼠肝损伤的影响。方法雄性SD大鼠60只,体重200~250g,随机分为三组:对照组,脂多糖组(LPS组,LPS 8mg/kg),GIK组(LPS 8mg/kg+GIK 4ml·kg^(-1)·h^(-1))。采用全自动生化仪检测腹腔注射LPS后3d和5d大鼠血清丙氨酸氨基转移酶(ALT)及天门冬氨酸氨基转移酶(AST)含量,ELISA法检测三组大鼠肝组织匀浆TNF-α含量,并行HE染色观察肝组织病理变化,TUNEL免疫荧光检测肝实质细胞凋亡情况。结果与注射后3d比较,注射后5dLPS组大鼠血清ALT、AST、肝组织匀浆TNF-α含量明显升高,而GIK组大鼠血清ALT、AST、肝组织匀浆TNF-α含量明显下降(P<0.05)。与对照组比较,注射后3dLPS组和GIK组大鼠血清ALT、AST、注射后5dLPS组大鼠血清ALT、AST明显升高(P<0.05),注射后3、5dLPS组和GIK组大鼠肝组织匀浆TNF-α含量、肝损伤等级评分、肝细胞凋亡指数明显升高(P<0.05)。与LPS组比较,注射后3dGIK组大鼠肝组织匀浆TNF-α含量、肝细胞凋亡指数明显降低(P<0.05),注射后5dGIK组大鼠血清ALT、AST、肝组织匀浆TNF-α含量、肝损伤等级评分、肝细胞凋亡指数明显降低(P<0.05)。结论腹腔注射LPS可引起大鼠肝损伤,导致肝功能改变及肝细胞破坏;GIK可减轻LPS诱导的大鼠肝损伤。

Objective To investigate if glucose-insulin-potassium （GIK）would relieve the liver injury induced by endotoxemia in rats.Methods Sixty SD male rats,weight 200-250g,were randomly divided into three groups （n = 20）：control group （group C）,lipopolysaccharide group （group LPS,LPS 8 mg/kg）and Glucose-insulin-potassium group（group GIK,8 mg/kg LPS＋GIK 4 ml·kg-1 ·h-1 ）.All the rats were injected with 20 mg/kg ketamine intraperitonealy before trial. Erythrocin was daubed on the wound to avoid infection.The rats of group LPS and group GIK were injected LPS 8 mg/kg intraperitoneal,then,rats in group LPS and group GIK received saline（4 ml·kg-1 ·h-1 ）or GIK（Glucose 200 g/L,Insulin 60 IU/L,KCL 60 mmol/L）infusion continuously. Liver and serum samples were collected on before injection,3 days after injection and 5 days after in-jection.Serum concentrations of ALT and AST were measured.TNF-αlpha of liver homogenate was detected by ELISA.The severity of liver damage was assessed by an approprite histopathological sco-ring system and apoptosis of parenchymal cells were assessed by TUNEL immunofluorescence assay. Results Compared with group control,the level of serum ALT and AST in group LPS and group GIK were significantly higher at 3 days after injection.The level of hepatic TNF-α,the hepatic damage score and the index of hepatic apoptosis in group LPS and group GIK were significantly higher on 3 days after injection and 5 days after injection.（P〈0.05）.Compared with group LPS,the level of hepatic TNF-αand the hepatocyte apoptosis rates decreased significantly in group GIK on 3 days after injection.The level of serum ALT and AST,hepatic TNF-α,the hepatic damage score and the hepatocyte apoptosis rates decreased significantly in group GIK at 5 days after injection（P 〈0.05）.Conclusion Intraperitoneal injection of endotoxin can cause liver injury in rats,resulting in the liver hepatdysfunction and hepatocyte damage.GIK has protective effects on LPS induced liver injury in rats.