摘要
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。
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.
出处
《中国医师杂志》
CAS
2012年第8期1046-1049,共4页
Journal of Chinese Physician
