c—Jun氨基末端激酶选择性抑制剂对雌激素诱导致妊娠期大鼠肝内胆汁淤积症的影响

目的探讨c-Jun氨基末端激酶（JNK）选择性抑制剂SP600125对雌激素诱导的妊娠期肝内胆汁淤积症大鼠肝组织内Bsep、Ntcp蛋白的表达情况及血清总胆汁酸浓度的影响。方法将孕15dSD大鼠皮下注射17—13-乙炔雌二醇建立ICP动物模型，并予以SP600125进行干预，检测各组孕鼠血清胆汁酸（TBA）、各组孕鼠肝脏组织c—Jun、胆盐输出泵（Bsep）及胆酸共转运蛋白（Ntcp）的表达水平。结果在ICP模型组中c．Jun的灰度值较正常对照组显著降低（101．05±5．20vs118．99±5．95，P〈0．05），给予SP600125干预后，干预组Bsep、Ntcp的表达较ICP模型组显著升高，且高干预组升高得更为明显（低剂量干预组Bsep：0．452±0．031V80．291±0．043，Ntcp：0．462±0．015V80．285±0．021，P〈0．05；高剂量干预组Bsep：0．568±0．038VS0．291±0．043；Ntcp：0．605±0．020VS0．285±0．021，P〈0．05），血清胆汁酸水平下降。结论在雌激素诱导ICP的动物模型中，SP600125可阻止c-Jun／AP-1表达升高，其可能参与了雌激素下调肝脏Bsep、Ntcp的表达机制。

Effect of a selective JNK inhibitor on pregnant rats with ethinylestradiol induced intrahepatic cholestasis

Objective To evaluate the influence of SP600125, a selective c-Jun N-terminal kinase （JNK） inhibitor, on the levels of serum total bile salt （TBA） and Bsep, Ntcp expression in the hepatic tis- sue of rats with ethinylestradiol induced intrahepatic cholestasis. Methods Rats pregnant for 15days were administered the subcutaneous injection of 17- b -estradiol propylene （EE） to modulate the ICP animal models, and be SP600125 to intervene. Testing the level of serum TBA and the expression of c-Jun, Bsep, Ntcp in the hepalatic tissue. Results The average gray values of c-Jun in the group of ICP models were significantly lower than the normal control group （ 101.05±5.20 vs 118.99±5.95, P 〈 0. 05 ）. After the intervention of SP600125, comparing with the group of ICP models , the expression of Bsep, Ntcp in the group of SP600125 intervention were significantly higher , and this change in the high dose of SP600125 in- tervention group was more obvious （ low dose intervention group Bsep ：0. 452 ± 0.031 vs 0. 291± 0. 043, Nt-cp：0. 462 ± 0. 015 vs 0. 285 ± 0. 021, P 〈 0. 05 ; high dose intervention group Bsep： 0. 568 ±0. 038 vs 0. 291± 0. 043, Ntep ：0. 605 ±0. 020 vs 0. 285 ± 0. 021, P 〈 0.05 ） , while the level of TBA in the serum was significantly lower. Conclusions Treatment with SP600125 can down-regulate the level of e-Jun/AP- 1 ,and it may participate in the lower expression of Bsep,Ntcp in the ICP rats which were induced by 17-bestradiol.