Expression And Significance Of HIF-1α And EPO In Placental Tissues Of Intrahepatic Cholestasis Of Pregnancy In Xining Region

Objective:By investigating the expression of hypoxia inducible factor-1 α(HIF-1α)and erythropoietin(EPO)in placental tissues of women with intrahepatic cholestasis of pregnancy(ICP)in Xining.Initially,we explored the mechanism of HIF-1 α and EPO in the pathogenesis of ICP in Xining,in order to provide some reference for the theoretical study of ICP in Xining area.Method: Fifty-three placenta samples were collected from ICP pregnant women(28 cases in the mild ICP and 25 cases in the severe ICP),30 cases of control group.All study samples were obtained from placental tissues of pregnant women delivering by cesarean section at the Affiliated Hospital of Qinghai University and the Red Cross Hospital of Qinghai Province from 09/2019 to 10/2020.HIF-1α and EPO protein expression in placental tissue detected by immunohistochemistry(IHC)、Western Blot(WB).The results of IHC analysis were analyzed by Image Pro Plus 6.0 software to calculate the mean optical density of HIF-1 α and EPO;WB bands to calculate the relative expression of HIF-1α,EPO protein.Data on general conditions,laboratory tests,and perinatal outcomes were also collected.Finally,the data were analyzed by t-test,ANOVA.Result:1.Analysis of general conditions,laboratory tests:(1)There were no significant differences in maternal age、BMI、FIB、PLT、DD、IBIL、total protein、albumin and globulin among the three groups(P > 0.05);(2)There were significant differences in TBA、ALT、DBIL、TBIL、ALP、AST、GGT、PT、APTT and TT among the three groups(P < 0.05);There were also statistical differences in gestational weeks and newborn weight between the three groups(P <0.05).2.Perinatal prognosis analysis:(1)The occurrence of low weight infants、preterm birth、and fetal distress is higher in ICP pregnancies than in normal pregnancies(P <0.05),(due to the small sample size of ICP,the mild and severe ICP groups were combined into ICP group).3.HIF-1α study results:(1)IHC: ICP pregnancies had higher mean optical density of HIF-1 α than normal pregnancies(P<0.05);the three groups were compared with each other,mild ICP is higher than in normal pregnancies,severe ICP is higher than normal and mild ICP pregnancies(P < 0.05).In ICP,the mean optical density of HIF-1α was positively correlated with TBA concentration(rs=0.675,P<0.05).(2)WB: HIF-1α protein expression is higher in ICP than in normal pregnancies(P< 0.05);the three groups were compared with each other,mild ICP is higher than in normal pregnancies(P < 0.05),severe ICP is higher than normal and mild ICP pregnancies(P < 0.05).In ICP,the relative expression of HIF-1α protein was positively correlated with TBA concentration(rs=0.432,P<0.05).4.EPO study results:(1)IHC: ICP pregnancies had higher mean optical density of EPO than normal pregnancies(P<0.05);the three groups were compared with each other,mild ICP is higher than in normal pregnancies,severe ICP is higher than normal and mild ICP pregnancies(P < 0.05).In ICP,the mean optical density of EPO was positively correlated with TBA concentration(rs=0.675,P<0.05).(2)WB: EPO protein expression is higher in ICP than in normal pregnancies(P <0.05);the three groups were compared with each other,mild ICP is higher than in normal pregnancies(P < 0.05),severe ICP is higher than normal and mild ICP pregnancies(P < 0.05).In ICP,the relative expression of EPO protein was positively correlated with TBA concentration(rs=0.432,P<0.05).5.Relationship between HIF-1α and EPO in ICP placental tissues:(1)IHC:The mean optical density of HIF-1α and EPO were positively correlated(r=0.525,P<0.05);(2)WB:The relative expression of HIF-1α and EPO protein was positively correlated(r=0.493,P<0.05).Conclusion:1.Pregnant women with ICP in Xining have coagulation and liver function abnormalities to some extent,and severe ICP has a greater impact on coagulation and liver function.2.The increased occurrence of low weight infants、preterm birth、and intrauterine hypoxia in ICP pregnant women in Xining was considered to be related to the toxic effects of bile acids or the hypoxic environment in Xining Region.3.HIF-1α was highly expressed in ICP placental tissues and positively correlated with TBA concentration,considering that HIF-1α was involved in the pathophysiological process of ICP in Xining.4.EPO was highly expressed in ICP placental tissues and positively correlated with TBA concentration,considering that EPO was involved in the pathophysiological process of ICP in Xining.5.The expression of HIF-1α and EPO were positively correlated in ICP placental tissues,and both were considered to be closely related to the pathogenesis of ICP in Xining.One of the reasons for the high EPO expression might be caused by the upregulation of HIF-1α expression.