中国医师杂志
中國醫師雜誌
중국의사잡지
JOURNAL OF CHINESE PHYSICIAN
2012年
8期
1046-1049
,共4页
JNK丝裂原活化蛋白激酶类%雌激素类%胆汁淤积,肝内
JNK絲裂原活化蛋白激酶類%雌激素類%膽汁淤積,肝內
JNK사렬원활화단백격매류%자격소류%담즙어적,간내
JNK mitogen-activated protein kinases%Estrogens%Cholestasis,intrahepatic
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15d SD大鼠皮下注射17-β-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 ±5.20 vs 118.99±5.95,P＜0.05),给予SP600125干预后,干预组Bsep、Ntep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 ±0.031 vs 0.291±0.043,Ntcp:0.462±0.015 vs0.285 ±0.021,P＜0.05；高剂量干预组Bsep:0.568 ±0.038 vs 0.291 ±0.043；Ntcp:0.605 ±0.020 vs 0.285±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.
目的 探討c-Jun氨基末耑激酶(JNK)選擇性抑製劑SP600125對雌激素誘導的妊娠期肝內膽汁淤積癥大鼠肝組織內Bsep、Ntcp蛋白的錶達情況及血清總膽汁痠濃度的影響.方法 將孕15d SD大鼠皮下註射17-β-乙炔雌二醇建立ICP動物模型,併予以SP600125進行榦預,檢測各組孕鼠血清膽汁痠(TBA)、各組孕鼠肝髒組織c-Jun、膽鹽輸齣泵(Bsep)及膽痠共轉運蛋白(Ntcp)的錶達水平.結果 在ICP模型組中c-Jun的灰度值較正常對照組顯著降低(101.05 ±5.20 vs 118.99±5.95,P＜0.05),給予SP600125榦預後,榦預組Bsep、Ntep的錶達較ICP模型組顯著升高,且高榦預組升高得更為明顯(低劑量榦預組Bsep:0.452 ±0.031 vs 0.291±0.043,Ntcp:0.462±0.015 vs0.285 ±0.021,P＜0.05；高劑量榦預組Bsep:0.568 ±0.038 vs 0.291 ±0.043；Ntcp:0.605 ±0.020 vs 0.285±0.021,P＜0.05),血清膽汁痠水平下降.結論 在雌激素誘導ICP的動物模型中,SP600125可阻止c-Jun/AP-1錶達升高,其可能參與瞭雌激素下調肝髒Bsep、Ntcp的錶達機製.
목적 탐토c-Jun안기말단격매(JNK)선택성억제제SP600125대자격소유도적임신기간내담즙어적증대서간조직내Bsep、Ntcp단백적표체정황급혈청총담즙산농도적영향.방법 장잉15d SD대서피하주사17-β-을결자이순건립ICP동물모형,병여이SP600125진행간예,검측각조잉서혈청담즙산(TBA)、각조잉서간장조직c-Jun、담염수출빙(Bsep)급담산공전운단백(Ntcp)적표체수평.결과 재ICP모형조중c-Jun적회도치교정상대조조현저강저(101.05 ±5.20 vs 118.99±5.95,P＜0.05),급여SP600125간예후,간예조Bsep、Ntep적표체교ICP모형조현저승고,차고간예조승고득경위명현(저제량간예조Bsep:0.452 ±0.031 vs 0.291±0.043,Ntcp:0.462±0.015 vs0.285 ±0.021,P＜0.05；고제량간예조Bsep:0.568 ±0.038 vs 0.291 ±0.043；Ntcp:0.605 ±0.020 vs 0.285±0.021,P＜0.05),혈청담즙산수평하강.결론 재자격소유도ICP적동물모형중,SP600125가조지c-Jun/AP-1표체승고,기가능삼여료자격소하조간장Bsep、Ntcp적표체궤제.
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 tissue 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 intervention group was more obvious ( low dose intervention group Bsep:0.452 ±0.031 vs 0.291 ±0.043,Ntcp: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,Ntcp: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 c-Jun/AP-1,and it may participate in the lower expression of Bsep、Ntcp in the ICP rats which were induced by 17-bestradiol.
