Effect Of A Selective JNK Inhibitor On The Bsep、Ntcp Expression In Pregnant Rats With Ethinylestradiol Induced Intrahepatic Cholestasis

Aims:To develop rats with intrahepatic cholestasis induced by17-b-estradiol.And then to evaluate the influence of selective AP-1inhibitor SP600125on the expression of c-Jun、Bsep、Ntcp in the hepalatic tissue and the levels of serum total bile salt(TBA) alanineaminotransferase(ALT)、aspartateaminotransferase(AST).Methods:Forty SD pregnant rats were randomly assigned to five groups(A-E):group A(Control)、group B(EE induced ICP)、group C(DMSO control)、group D (low dosage of SP600125)、group E(large dosage of SP600125). From day15to day19of gestation, rats in Group B to group E were only injected with the0.1%solution of ethinyl estradiol(EE) in propylene glycol(PG) subcutaneously at a dose of2.5ml kg-1d-1to modulate the ICP animal models;those in group A were injected with the propylene glycol(PG) subcutaneously at a dose of2.5ml·kg-1·d-1.Rats in group D and group E also received intraperitoneal SP600125injection(5mg/kg or10mg/kg,2h before the induction of ICP with EE). Rats in Group C only received DMSO. The animals were sacrificed on the5thday, and the changes of c-Jun was measured by immunohistochcmistry, while the Bsep、Ntcp were measured by Western Blotting; the Level of AST、 ALT、TBA were measured by enzymology.Results:The levels of TBA (42.08±8.83)、(AST158.67±47.02)、ALT (96.98±28.22) and c-Jun (101.05±5.20) in group B were significantly higher than those in the group A(TBA14.80±3.39,AST91.25±14.92,ALT41.46±3.78c-Jun118.99±5.95,p<0.05, respectively), Those in group E(TBA26.56±7.66,AST111.48±20.26,ALT64.94±14.39c-Jun113.96±5.50)were significantly lower than in the group C(TBA42.89±8.73,AST158.92±45.91,ALT95.16±27.10c-Jun102.11±5.63P<0.05, respectively). those targets (TBA34.31±7.59c-Jun107.96±5.36) in group D were significantly lower than in the group C, while those (AST140.86±38.33ALT86.50±21.37) compared with group C have no statistical significance (p>0.05)Bsep(0.291±0.043)and Ntcp(0.285±0.021) in group B were significantly lower than those in the group A (Bsep0.629±0.108Ntcp0.657±0.075p<0.05respectively). those in the group D (Bsep0.452±0.031Ntcp0.462±0.015) and group E(Bsep0.560±0.038Ntcp0.605±0.020) were significantly higher than that in group C(Bsep0.290±0.035Ntcp0.263±0.017p<0.05respectively). The Bsep、Ntcp in group B and group C were no significantly different (p>0.05)Conclusion: (1) JNK may participate the lower expression of Bsep、Ntcp in the ICP rats which induced by17-b-estradiol, and the possible mechanism is by activating the AP-1.(2) The JNK inhibitor SP600125can inhibitor the lower expression of Bsep、Ntcp by17-b-estradiol,and relieve the degree of Cholestasis.