Abstract： Objective To investigate the changes of umbilical cord and the vasoactive substance in umbilical vein in intrahepatic cholestasis of pregnancy.Methods By HE staining method we analyzed the pathologic change of umbilical cord of 25 women with intrahepatic cholestasis of pregnancy(ICP)and fetal distress(ICP fetal distress group),25 ICP women without fetal distress group(ICP control group)and 27 normal pregnancies(control group).The nitric oxide synthase(NOS)and endothelin-1(ET-1)were detected in human umbilical vein endothelial cells(HUVEC)by immunohistochemistry method.Umbilical vein total bile acid(TBA)and NOS and ET-1 were measured.Resuits (1)A remarkable high TBA level was found in umbilical vein in ICP,and it was higher in ICP fetal distress group(19.0±2.3)μmol/L than in ICP control group(9.0±1.7)μmol/L(P＜0.05);it was higher in ICP control group than the control group(4.4±1.5)μmol/L(P＜0.05).(2)A significant difference was found in the endotheliocytes of umbilical vein in ICP fetal distress group compared with ICP control group.The ratio of cells with pathological changes in ICP fetal distress group(92％,23/25)was higher than ICP control group(68％,17/25;P＜0.05).The occurrence of the pathological changes was associated with TBA.(3)The expression of eNOS in ICP fetal distress group 0.09±0.06 was lower than in ICP control group 0.21±0.08(P＜0.05),and it was lower in ICP control group than in control group 0.47±0.07(P＜0.05).In contrast.the expression of ET-1 in ICP fetal distress group 0.49±0.08 was higher than in ICP control group 0.32±0.07(P＜0.05),and it was higher in ICP control group than control group 0.14±0.06(P＜0.05).The expression of inducible nitric oxide synthase(iNOS)in ICP fetal distress group 0.20±0.04 and ICP control group 0.21±0.05 was lower than in control group 0.26±0.04(P＜0.05),but no significant difference was found in ICP fetal distress group and ICP control group(P＞0.05).(4)The expression of eNOS,iNOS and ET-1 was correlated with umbilical vein TBA in ICP(r1=-0.88,r2=-0.45,r3=0.79;P＜0.01),respectively.Conclusions High level of TBA in ICP is harmful to the umbilical vein endothelium,which is correlated with the raised expression of ET-1.and the decreased expression of eNOS,and iNOS in human umbilical cord endothelium cells.All these changes of umbilical vein may be associated with the occurrence of fetal distress in ICP.