ABSTRACT
Objective To investigate the therapeutic effects of emodin on acute cholestatic hepatitis and mec-hanism thereof. Methods Fifty Sprague - Dawley (SD)rats were randomly divided into 5 groups and were treated with emodin,ursodeoxycholic acid,dexamethasone,or normal saline respectively for 4 days. On the fifth day gastric perfusion of alpha - naphthylisothiocyanate(ANIT)was performed to establish models of choiestatic hepatitis. Four to six hours after the establishment of model the above mentioned agents were given continuously. Forty - eight hours after the model establishment blood samples were collected from abdominal aorta to examine the total bilirubin(TB),direct bilirubin (DB),alanine aminotransferase(ALT),total bile acid(TBA),aspartate aminotransferase(AST),alkaline phosphatase (ALP),gamma glutamine transferase(GGT). Specimen of liver was collected to undergo pathological examination. Real - time PCR was used to detect the mRNA expression of farnesoid X receptor(FXR),small heterodimer partner (SHP ),bile salt export pump (BSEP ),uridine diphosphate glucuronosyltransferase 2 family polypeptide B4 (UGT2B4). Results The serum levels of total bilirubin (TB),direct bilirubin (DB),alanine aminotransferase (ALT),total bile acids (TBA),aspartate aminotransferase (AST),and alkaline phosphatase (ALP)of the model group were respectively (68. 1 ± 26. 1)μmol/ L,(46. 3 ± 20. 1)μmol/ L,(483 ± 228)U/ L,(159. 1 ± 57. 9)μmol/L,(2. 0 ± 0. 5)U/ L,(996 ± 382)U/ L,(324 ± 120)U/ L. The levels of TB,DB,ALT,TBA,AST,ALP of the emodin group were respectively (15. 0 ± 8. 7)μmol/ L,(10. 8 ± 3. 9)μmol/ L,(147 ± 71)U/ L,(60. 1 ± 22. 7)μmol/ L, (295 ± 104)U/ L,(222 ± 59)U/ L,and were all significantly lower than those of the model group (all P < 0. 05). The levels of TB,DB,ALT,TBA,AST,GGT,ALP of the emodin group were all significantly lower than those of the ursode-oxycholic acid group (all P < 0. 05). The levels of TB,DB,ALT,TBA,GGT,AST were all significantly lower than those of the dexamethasone group (all P < 0. 01). The expression levels of FXR,SHP,BSEP,UGT2B4 mRNA in the emodin group (1. 087 ± 0. 285,0. 892 ± 0. 390,0. 902 ± 0. 149,1. 785 ± 0. 403)were all significantly higher than those of the model group (0. 152 ±0. 088,0. 559 ±0. 194,0. 561 ±0. 123,0. 177 ±0. 039,all P <0. 05). Conclusions By decreasing the levels of TB,DB,ALT,TBA,AST,ALP and reducing pathological changes,emodin has a protective effect on cholestatic hepatitis. It has better effects than ursodeoxycholic acid and dexamethasone. These effects may be due to promoting FXR,SHP,BSEP and UGT2B4 expression.
ABSTRACT
T of PRF1 gene was found.There was a strong linkage disequilibrium among the SNPs of GZMB.Conclusion:7 SNPs were detected in PRF1 and GZMB genes all together,two of which were first identified. There is apparent linkage disequilibrium among SNPs of PRF1and GZMB gene in Han population of Chongqing.