中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2008年
6期
453-456
,共4页
兰易%刘建%程浩%邹姝丽%甘晓玲
蘭易%劉建%程浩%鄒姝麗%甘曉玲
란역%류건%정호%추주려%감효령
胆汁淤积,肝内%小异二聚体伴侣%胆固醇7a-羟化酶
膽汁淤積,肝內%小異二聚體伴侶%膽固醇7a-羥化酶
담즙어적,간내%소이이취체반려%담고순7a-간화매
Cholestasis,intrahepatic%Small heterodimer partner%Cholesterol-7-hydroxylase
目的 建立妊娠期肝内胆汁淤积症孕鼠模型,检测小异二聚体伴侣(SHP)及其靶基因胆固醇7a-羟化酶(CYP7A1)在肝脏的表达,探讨其在妊娠期肝内胆汁淤积症发病机制中的作用.方法 孕15d SD大鼠30只随机分为对照组和雌激素组,每组15只.用药前和用药后第5天分别检测血清中ALT、 AST、碱性磷酸酶、总胆汁酸、总胆红素、直接胆红素水平,同时观察肝脏形态学变化,并应用RT-PCR和Western blot分别检测肝脏SHP和CYP7A1的mRNA和蛋白质的表达.结果 雌激素组用药后ALT、 AST、碱性磷酸酶、总胆汁酸、总胆红素、直接胆红素比用药前明显升高(P<0.01);对照组用药前后各血清生物化学指标无明显变化(P>0.05).雌激素组孕鼠肝脏出现肝内胆汁淤积表现,对照组肝脏形态、结构正常.雌激素组和对照组SHP mRNA分别为0.4865±0.0237和0.3657±0.0317, CYP7A1 mRNA分别为0.4311±0.0157和0.3285±0.0123,差异均有统计学意义(P<0.01).雌激素组和对照组SHP蛋白表达分别为0.5033±0.0274和0.3762±0.0284, CYP7A1蛋白表达分别为0.4802±0.0217和0.3570±0.0175,差异均有统计学意义(P<0.01).结论 雌激素诱导的胆汁淤积促进肝脏SHP及其靶基因CYP7A1表达增加,导致胆汁酸合成进一步增加,从而引发胆汁淤积,这可能是妊娠期肝内胆汁淤积症发病机制之一.
目的 建立妊娠期肝內膽汁淤積癥孕鼠模型,檢測小異二聚體伴侶(SHP)及其靶基因膽固醇7a-羥化酶(CYP7A1)在肝髒的錶達,探討其在妊娠期肝內膽汁淤積癥髮病機製中的作用.方法 孕15d SD大鼠30隻隨機分為對照組和雌激素組,每組15隻.用藥前和用藥後第5天分彆檢測血清中ALT、 AST、堿性燐痠酶、總膽汁痠、總膽紅素、直接膽紅素水平,同時觀察肝髒形態學變化,併應用RT-PCR和Western blot分彆檢測肝髒SHP和CYP7A1的mRNA和蛋白質的錶達.結果 雌激素組用藥後ALT、 AST、堿性燐痠酶、總膽汁痠、總膽紅素、直接膽紅素比用藥前明顯升高(P<0.01);對照組用藥前後各血清生物化學指標無明顯變化(P>0.05).雌激素組孕鼠肝髒齣現肝內膽汁淤積錶現,對照組肝髒形態、結構正常.雌激素組和對照組SHP mRNA分彆為0.4865±0.0237和0.3657±0.0317, CYP7A1 mRNA分彆為0.4311±0.0157和0.3285±0.0123,差異均有統計學意義(P<0.01).雌激素組和對照組SHP蛋白錶達分彆為0.5033±0.0274和0.3762±0.0284, CYP7A1蛋白錶達分彆為0.4802±0.0217和0.3570±0.0175,差異均有統計學意義(P<0.01).結論 雌激素誘導的膽汁淤積促進肝髒SHP及其靶基因CYP7A1錶達增加,導緻膽汁痠閤成進一步增加,從而引髮膽汁淤積,這可能是妊娠期肝內膽汁淤積癥髮病機製之一.
목적 건립임신기간내담즙어적증잉서모형,검측소이이취체반려(SHP)급기파기인담고순7a-간화매(CYP7A1)재간장적표체,탐토기재임신기간내담즙어적증발병궤제중적작용.방법 잉15d SD대서30지수궤분위대조조화자격소조,매조15지.용약전화용약후제5천분별검측혈청중ALT、 AST、감성린산매、총담즙산、총담홍소、직접담홍소수평,동시관찰간장형태학변화,병응용RT-PCR화Western blot분별검측간장SHP화CYP7A1적mRNA화단백질적표체.결과 자격소조용약후ALT、 AST、감성린산매、총담즙산、총담홍소、직접담홍소비용약전명현승고(P<0.01);대조조용약전후각혈청생물화학지표무명현변화(P>0.05).자격소조잉서간장출현간내담즙어적표현,대조조간장형태、결구정상.자격소조화대조조SHP mRNA분별위0.4865±0.0237화0.3657±0.0317, CYP7A1 mRNA분별위0.4311±0.0157화0.3285±0.0123,차이균유통계학의의(P<0.01).자격소조화대조조SHP단백표체분별위0.5033±0.0274화0.3762±0.0284, CYP7A1단백표체분별위0.4802±0.0217화0.3570±0.0175,차이균유통계학의의(P<0.01).결론 자격소유도적담즙어적촉진간장SHP급기파기인CYP7A1표체증가,도치담즙산합성진일보증가,종이인발담즙어적,저가능시임신기간내담즙어적증발병궤제지일.
Objectives To investigate the expressions of small heterodimer partner (SHP) and target gene cholesterol-7-hydroxylase (CYP7A1) in livers of rats with intrahepatic cholestasis of pregnancy (ICP), and to study the mechanism of ICP. Methods Thirty SD rats (pregnant for 15 days) were equally and randomly divided into two groups: an estradiol benzoate (EB) group and a normal saline (NS) group. Two ml blood was drawn from each rat before and on the 5th day after medicine administration to measure the levels of ALT, AST, ALP, TBA, TBIL, and DBIL. After delivery, the histopathological changes of the mother rat livers were studied. The mRNA and protein expressions of SHP and CYP7A1 in the livers were determined by RT-PCR and Western blot. Results (1) In the EB group, the serum levels of ALT, AST, ALE TBA, TBil, and DBil after EB administration increased significantly (P<0.01), but there were no significant changes in the NS group (P>0.05); (2) Intrahepatic cholestasis appeared in the EB group, but not in the NS group; (3) The mRNA expressions of SHP and CYP7A1 were significantly higher in the EB group than in the NS group [(SHPmRNA: NS 0.365±0.0317 vs EB 0.4865±0.0237, P<0.01), (CYP7A1 mRNA: NS 0.3570±0.0175 vs EB 0.4802±0.0217, P<0.01)]; (4) The protein expressions of SHP and CYP7A1 were also higher in the EB group than that in the NS group [(SHP: NS 0.3762±0.0284 vs EB 0.5033±0.0274, P<0.01),(CYP7AI: NS 0.3570±0.0175 vs EB 0.4802±0.0217, P<0.01)]. Conclusion Estrogen induces ICP in rats. The mRNA and protein expressions of SHP and CYP7A1 in livers of the ICP rats were increased, which causes more bile acids to be synthesized. This may be one of the mechanisms of ICP.
