中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2010年
12期
927-930
,共4页
胆汁淤积,肝内%妊娠,动物%代谢%法尼醇X受体%过氧化物酶增殖体激活受体α
膽汁淤積,肝內%妊娠,動物%代謝%法尼醇X受體%過氧化物酶增殖體激活受體α
담즙어적,간내%임신,동물%대사%법니순X수체%과양화물매증식체격활수체α
Cholestasis,intrahepatic%Pregnancy,animal%Metabolism%Farnesoid X receptor%Peroxisome proliferators-activated receptor alpha
目的 探讨法尼醇X受体(FXR)、过氧化物酶增殖体激活受体α(PPAR α)与胆固醇7 α羟化酶(CYP7A1)、胆固醇27 α羟化酶(CYP27A1)、胆固醇12 α羟化酶(CYP8B1)mRNA在妊娠期肝内胆汁淤积孕鼠肝脏中的表达及其意义.方法将60只清洁级SD大鼠自孕第13天均分为3组,对照组:皮下注射精制植物油2.0ml·kg-1·d-1;未治疗组:皮下注射17-α-乙炔雌二醇1.25 mg·kg-1·d-1;治疗组:皮下注射17-α-乙炔雌二醇1.25 mg·kg-1·d-1,孕第17天起给予非诺贝特50 mg·kg-1·d-1灌胃.3组孕鼠分别于妊娠第13、17、21天断尾采血2 ml检测血清生物化学指标,并于妊娠第21天处死,提取肝脏组织.应用酶联免疫吸附法检测3组孕鼠血清中的胆酸水平;用实时定量PCR技术检测各组PPARα、FXR、CYP7A1、CYP27A1、CYP8B1 mRNA的表达量.多组间的比较用方差分析,多组的两两间比较用Student-Newman-Keuls法检验,两组数据间比较用t检验.结果 妊娠第17天,对照组、未治疗组、治疗组的胆汁酸水平分别为(26.6±2.3)μmol/L、(68.7±4.2)μmol/L、(69.5±3.8)μmol/L,未治疗组和治疗组胆汁酸水平与对照组比较,t值分别为2.516、2.642,P值均＜0.05,差异均有统计学意义.治疗组与未治疗组之间胆汁酸水平比较,t=1.835,P＞0.05,差异无统计学意义;妊娠第21天,对照组、未治疗组、治疗组胆汁酸水平分别为(27.1±3.2) mol/L、(69.4±3.7)μmol/L、(48.5±4.8)μmol/L,3组比较,F=7.81,P＜0.05,差异有统计学意义.对照组、未治疗组、治疗组中CYP7A1 mRNA的相对表达量分别为0.75±0.02、1.55±0.03、1.25±0.01,FXR mRNA的相对表达量分别为1.25±0.03、1.75±0.02、1.65±0.05,CYP27A1 mRNA的相对表达量分别为0.65±0.03、2.45±0.01、1.65±0.02,CYP8B1 mRNA的相对表达量分别为1.50±0.02、2.15±0.01、1.75±0.03,PPARαmRNA的相对表达量分别为1.45±0.02、0.85±0.02、1.35±0.01.CYP7A1、FXR、CYP27A1、CYP8B1 mRNA在未治疗组中的表达量与对照组相比,q值分别为6.554、5.613、8.126和6.143,P值均＜0.05,差异均有统计学意义.未治疗组中PPAR α mRNA的表达量与对照组相比,q=6.126,P＜0.01,差异有统计学意义.治疗组中CYP27A1、PPAR α mRNA、CYP8B1 mRNA水平与未治疗组相比,q值分别为6.346、7.231和5.892,P值均＜0.05,差异均有统计学意义.结论胆汁酸的合成与代谢调节机制存在障碍,是导致妊娠期肝内胆汁淤积症发生的原因之一,用PPAR α的激动剂对其有一定疗效.
目的 探討法尼醇X受體(FXR)、過氧化物酶增殖體激活受體α(PPAR α)與膽固醇7 α羥化酶(CYP7A1)、膽固醇27 α羥化酶(CYP27A1)、膽固醇12 α羥化酶(CYP8B1)mRNA在妊娠期肝內膽汁淤積孕鼠肝髒中的錶達及其意義.方法將60隻清潔級SD大鼠自孕第13天均分為3組,對照組:皮下註射精製植物油2.0ml·kg-1·d-1;未治療組:皮下註射17-α-乙炔雌二醇1.25 mg·kg-1·d-1;治療組:皮下註射17-α-乙炔雌二醇1.25 mg·kg-1·d-1,孕第17天起給予非諾貝特50 mg·kg-1·d-1灌胃.3組孕鼠分彆于妊娠第13、17、21天斷尾採血2 ml檢測血清生物化學指標,併于妊娠第21天處死,提取肝髒組織.應用酶聯免疫吸附法檢測3組孕鼠血清中的膽痠水平;用實時定量PCR技術檢測各組PPARα、FXR、CYP7A1、CYP27A1、CYP8B1 mRNA的錶達量.多組間的比較用方差分析,多組的兩兩間比較用Student-Newman-Keuls法檢驗,兩組數據間比較用t檢驗.結果 妊娠第17天,對照組、未治療組、治療組的膽汁痠水平分彆為(26.6±2.3)μmol/L、(68.7±4.2)μmol/L、(69.5±3.8)μmol/L,未治療組和治療組膽汁痠水平與對照組比較,t值分彆為2.516、2.642,P值均＜0.05,差異均有統計學意義.治療組與未治療組之間膽汁痠水平比較,t=1.835,P＞0.05,差異無統計學意義;妊娠第21天,對照組、未治療組、治療組膽汁痠水平分彆為(27.1±3.2) mol/L、(69.4±3.7)μmol/L、(48.5±4.8)μmol/L,3組比較,F=7.81,P＜0.05,差異有統計學意義.對照組、未治療組、治療組中CYP7A1 mRNA的相對錶達量分彆為0.75±0.02、1.55±0.03、1.25±0.01,FXR mRNA的相對錶達量分彆為1.25±0.03、1.75±0.02、1.65±0.05,CYP27A1 mRNA的相對錶達量分彆為0.65±0.03、2.45±0.01、1.65±0.02,CYP8B1 mRNA的相對錶達量分彆為1.50±0.02、2.15±0.01、1.75±0.03,PPARαmRNA的相對錶達量分彆為1.45±0.02、0.85±0.02、1.35±0.01.CYP7A1、FXR、CYP27A1、CYP8B1 mRNA在未治療組中的錶達量與對照組相比,q值分彆為6.554、5.613、8.126和6.143,P值均＜0.05,差異均有統計學意義.未治療組中PPAR α mRNA的錶達量與對照組相比,q=6.126,P＜0.01,差異有統計學意義.治療組中CYP27A1、PPAR α mRNA、CYP8B1 mRNA水平與未治療組相比,q值分彆為6.346、7.231和5.892,P值均＜0.05,差異均有統計學意義.結論膽汁痠的閤成與代謝調節機製存在障礙,是導緻妊娠期肝內膽汁淤積癥髮生的原因之一,用PPAR α的激動劑對其有一定療效.
목적 탐토법니순X수체(FXR)、과양화물매증식체격활수체α(PPAR α)여담고순7 α간화매(CYP7A1)、담고순27 α간화매(CYP27A1)、담고순12 α간화매(CYP8B1)mRNA재임신기간내담즙어적잉서간장중적표체급기의의.방법장60지청길급SD대서자잉제13천균분위3조,대조조:피하주사정제식물유2.0ml·kg-1·d-1;미치료조:피하주사17-α-을결자이순1.25 mg·kg-1·d-1;치료조:피하주사17-α-을결자이순1.25 mg·kg-1·d-1,잉제17천기급여비낙패특50 mg·kg-1·d-1관위.3조잉서분별우임신제13、17、21천단미채혈2 ml검측혈청생물화학지표,병우임신제21천처사,제취간장조직.응용매련면역흡부법검측3조잉서혈청중적담산수평;용실시정량PCR기술검측각조PPARα、FXR、CYP7A1、CYP27A1、CYP8B1 mRNA적표체량.다조간적비교용방차분석,다조적량량간비교용Student-Newman-Keuls법검험,량조수거간비교용t검험.결과 임신제17천,대조조、미치료조、치료조적담즙산수평분별위(26.6±2.3)μmol/L、(68.7±4.2)μmol/L、(69.5±3.8)μmol/L,미치료조화치료조담즙산수평여대조조비교,t치분별위2.516、2.642,P치균＜0.05,차이균유통계학의의.치료조여미치료조지간담즙산수평비교,t=1.835,P＞0.05,차이무통계학의의;임신제21천,대조조、미치료조、치료조담즙산수평분별위(27.1±3.2) mol/L、(69.4±3.7)μmol/L、(48.5±4.8)μmol/L,3조비교,F=7.81,P＜0.05,차이유통계학의의.대조조、미치료조、치료조중CYP7A1 mRNA적상대표체량분별위0.75±0.02、1.55±0.03、1.25±0.01,FXR mRNA적상대표체량분별위1.25±0.03、1.75±0.02、1.65±0.05,CYP27A1 mRNA적상대표체량분별위0.65±0.03、2.45±0.01、1.65±0.02,CYP8B1 mRNA적상대표체량분별위1.50±0.02、2.15±0.01、1.75±0.03,PPARαmRNA적상대표체량분별위1.45±0.02、0.85±0.02、1.35±0.01.CYP7A1、FXR、CYP27A1、CYP8B1 mRNA재미치료조중적표체량여대조조상비,q치분별위6.554、5.613、8.126화6.143,P치균＜0.05,차이균유통계학의의.미치료조중PPAR α mRNA적표체량여대조조상비,q=6.126,P＜0.01,차이유통계학의의.치료조중CYP27A1、PPAR α mRNA、CYP8B1 mRNA수평여미치료조상비,q치분별위6.346、7.231화5.892,P치균＜0.05,차이균유통계학의의.결론담즙산적합성여대사조절궤제존재장애,시도치임신기간내담즙어적증발생적원인지일,용PPAR α적격동제대기유일정료효.
Objective To study the expressions of FXR, PPARα and Bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats. Methods 60 clean SD pregnant rats were selected and divided randomly into three groups. Since the 13th day of pregnancy rats in control group were injected then were treated with fenofibrate for another four days untill the 21th day. All rats were killed at the 21th day and livers were collected for study. The levels of serum TBA were examined by ELISA. The mRNA expressions of PPAR α, FXR, CYP7A1, CYP27A1 and CYP8B1 were examined by real-time PCR. Results (1)The levels of TBA were significantly higher in no-treated group (68.7 ± 4.2) μmol/L and treated group (69.5 ± 3.8) μmol/L compared with that of control group (26.6 ± 2.3) μmol/L at the 17th day (P ＜ 0.05) and no difference found between treated and no-treated groups (P ＞ 0.05). The levels of TBA were higher in notreated group (69.4 ± 3.7) μmol/L and treated group (48.5 ± 4.8) μmol/L as compared to control group (27.1 ± 3.2) μmol/L at the 21th day (P ＜ 0.05). The lever of TBA was significantly lower in Treated group compared with No-treated group (P ＜ 0.05). (2) The mRNA expressions of CYP7A1, FXR, CYP27A1 and CYP8B1 increased in No-treated group (1.55 ± 0.03, 1.75 ± 0.02, 2.45 ± 0.01, 2.15 ± 0.01, respectively)and were all higher as compared to control group (0.75 ± 0.02, 1.25 ± 0.03, 0.65 ± 0.03, 1.50 ± 0.02,respectively) (P ＜ 0.05). However, the mRNA expression of PPAR α decreased in No-treated group (0.85 ±0.02) compared with control group (1.45 ± 0.02) (P ＜ 0.05). The mRNA expressions of CYP27A1, PPAR α and CYP8B1 increased in treated group (1.25 ± 0.01, 1.65 ± 0.05, 1.65 ± 0.02, respectively) and were all higher than that of control group (P ＜ 0.05). Conclusion Abnormal expressions of CYP7A1, FXR, CYP27A1,CYP8B1 and PPARα may play a role in pathogenesis of estrogen-induced intrahepatic cholestasis. Activator of PPAR α may be used as therapeutical drug for ICP.
