Protective effect of spleen polypeptide on acute liver injury induced by azithromycin combined with acetaminophen in mice / 国际药学研究杂志

ABSTRACT

Objective: To investigate the effect of spleen polypeptide on liver injury induced by azithromycin combined with acetaminophen in mice. Methods: The mice were randomly divided into 6 groupsthe normal control group,model group,spleen polypeptide dose groups[25,50,and 100 mg/ (kg•d)],and silybin positive drug group[70 mg/ (kg•d)]. The mice in the normal con- trol group were injected with normal saline in the whole animal experiment. The mice in the model group,spleen polypeptide dose group and positive group were treated respectively with normal saline,spleen polypeptide by caudal vein injection and silybin by ga- vage for 4 d. After 2 hours of administration on day 4,all mice except those in the normal control group were given acetaminophen (350 mg/kg)and azithromycin(280 mg/kg)by gavage for 7 d. The organ index of mice was calculated,and the plasma alanine amino- transferase(ALT),aspartate aminotransferase(AST),ALT/AST,urea nitrogen(BUN),creatinine(CREA),uric acid(UA),total protein(TP),albumin(ALB),globulin(GLO)and albumin /globulin(A/G)in mice were measured. The superoxide dismutase (SOD),catalase(CAT)and glutathione peroxidase(GSH-PX)activity of liver tissue homogenate were measured. The expression of Bax and Bcl-2 protein in hepatocytes was measured by Western blot. Results: Compared with the normal control group,the liver in- dex of the model group was increased significantly(P<0.01),and the spleen and kidney indices were decreased(P<0.05,P< 0.01). Compared with the model group,the liver index of the spleen polypeptide 100 mg/ (kg•d)group was decreased significantly (P<0.01),the spleen and the kidney index of the spleen polypeptide 25,50 and 100 mg/ (kg•d)groups were increased significantly (P<0.01),and the liver index of positive drug group was decreased significantly(P<0.01). Compared with the normal control group,the plasma levels of ALT,AST,TP,GLO,UA,BUN and CREA were increased significantly in the model mice(P<0.05, P<0.01),and the plasma levels of ALB and A/G were decreased(P<0.05,P<0.01). Compared with the model group,the plasma AST levels of the spleen polypeptide 25,50,100 mg/ (kg•d)and positive drug groups were decreased significantly(P<0.01),and the plasma ALT,AST,TP,GLO,UA,BUN and CREA levels of the spleen polypeptide 100 mg/ (kg•d)and positive drug groups were decreased(P<0.05,P<0.01),and the plasma levels of ALB and A/G were increased(P<0.05). Compared with the normal control group,hepatic levels of SOD,CAT,GSH-Px activity and the expression of Bcl-2 were decreased significantly(P<0.01),and the expression of Bax was increased significantly(P<0.01). Compared with the model group,the activity of GSH-Px,CAT,SOD and the expression of Bal-2 in liver of the spleen polypeptide[25,50 and 100 mg/ (kg•d)]groups and the positive group were increased significantly(P<0.01),and the expression of Bax decreased significantly(P<0.01). Conclusion: Spleen polypeptide could im- prove acute liver injury induced by azithromycin combined with acetaminophen in mice.