title: Lowering blood ammonia prevents hepatocyte injury and apoptosis.
abstract: To study hepatocyte injure through establishing the rat model of acute hepatic failure (ALF). ALF rat model was established by administration with D-galactosamine and LPS, and then giving lowering blood ammonia (LBA) treatment. Besides, the intervention groups were injected with ornithine and aspartate. The control groups were injected saline. Blood ammonia, ALT, AST, TNF-α and IL-6 in blood samples were test at 12 hrs and 24 hrs after treatment with LBA. Hepatocyte apoptosis were tested by TUNEL and DNA Ladder. Expression of P53 and SPP1 were detected by RT-PCR.
  
  
  RESULTS
  showed that blood ammonia in hepatic failure group and intervention group compared with blank control group was significantly increased at 12 h, 24 h; intervention group compared with hepatic failure group was significantly reduced (P<0.05). Serum ALT, AST in 24 h group were higher than 12 h. 12 h intervention group was decreased compared with hepatic failure group, but there was no significant statistically difference (P>0.05). 24 h intervention group compared with hepatic failure group was significantly reduced (P<0.05). Except the control group, DNA ladder and the TUNEL results showed hepatocyte apoptosis rate increased in 24 h compared with 12 h. Intervention group compared with hepatic failure group was significantly reducing (P<0.05). IL-6, TNF-α, p53 expression levels were increased with time (24 h>12 h). The hepatic failure and intervention group compared with blank control group was significantly increased; Intervention group compared with hepatic failure group was significantly reducing (P<0.05). SPP1 gene was high expression in ALF rat model. SPP1 level in hepatic failure and intervention group compared with control group was significantly increased, and intervention group compared with hepatic failure group was significantly reducing (P<0.05). In conclusion, hepatocyte apoptosis is an important pathological change in ALF rat mode, and lowing ammonia can reduce liver injury and apoptosis. Blood TNF-α, IL-6 and SPP1 may be more sensitive injure indicators.
authors.affiliation: Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Key-Disiplines Laboratory Clinical-Medcine Henan Zhengzhou 450052, Henan, China.
authors.forename: Guanmin
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan, China.
authors.forename: Zujiang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan, China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Key-Disiplines Laboratory Clinical-Medcine Henan Zhengzhou 450052, Henan, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Key-Disiplines Laboratory Clinical-Medcine Henan Zhengzhou 450052, Henan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan, China.
authors.forename: Kelei
authors.initials: K
authors.lastname: Guan
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan, China.
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Kan
keywords: Acute liver failure; apoptosis; blood ammonia