Study On The Pathogenesis Of Oxidative Stress-Related Factors Nrf2 And HSP70 And Intrahepatic Cholestasis Of Pregnancy

Objective:To measure the expressions of oxidative stress-related factors Nrf2 mRNA and HSP70 mRNA in the placenta of patients with intrahepatic cholestasis of pregnancy(ICP),and to explore the role of mitochondrial oxidative stress in the pathogenesis of ICP.Methods:The placental tissue samples of ICP patients who were treated in the affiliated hospital of north Sichuan medical college and terminated pregnancy by cesarean section were collected from March,2018 to May,2019,including 30 mild cases and 30 severe cases.In addition,30 placental tissue samples of single normal pregnant women excluding surgical complications and pregnancy-related diseases in the same period were collected as control group.The expression of Nrf2 mRNA and HSP70 mRNA in the placental tissue was determined by RT-qPCR.The results were analyzed by statistical methods such as variance analysis,t-test,and chi-square test,and the difference was statistically significant(P<0.05).Results:(1)Nrf2 mRNA and HSP70 mRNA were expressed in placental tissues of ICP patients and normal pregnant women;(2)The expressions of Nrf2 mRNA and HSP70 mRNA in the placenta tissues of the mild and severe ICP group were higher than those of control group,and the expressions of placental tissues of ICP severe group were higher than those of mild group,and the expression differences between groups were statistically significant(P<0.01);(3)The expressions of Nrf2 mRNA and HSP70 mRNA in placenta of ICP group were positively correlated(r=0.980,P<0.05);(4)Compared with the average age of pregnant women in the ICP group and the control group,the difference was not statistically significant(P>0.05),and compared with the average gestational week of the ICP group and the control group,the difference was statistically significant(t=-6.487,P<0.01).The average gestational week was significantly lower than that of the control group and the mild group,and there was no significant difference in the average gestational week between the ICP mild group and the control group.(5)There was a statistically significant difference in the meconium-stained amniotic fluid between the ICP group and the control group.(χ2=9.317,P<0.05).Conclusions:1.Both Nrf2 mRNA and HSP70 mRNA are expressed in the placental tissue of the ICP group and the control group,and Nrf2 and HSP70 are found in human placental trophoblasts.2.The expressions of Nrf2 mRNA and HSP70 mRNA in ICP placenta tissue were higher than those in the normal control group,suggesting that mitochondrial oxidative stress in trophoblasts is related to ICP.It is speculated that under the stimulation of high bile acid,the mitochondria of trophoblasts undergo oxidative stress reaction.When the antioxidant defense system is decompensated,mitochondrial-mediated apoptosis pathways will be activated to cause apoptosis,eventually leading to adverse pregnancy outcome.3.There is a positive correlation between the expression level of Nrf2 mRNA and HSP70 mRNA in ICP placenta tissue,suggesting that Nrf2 and HSP70,mitochondrial oxidative stress-related factors in trophoblasts,may interact with each other,and jointly play an anti-oxidative stress role and participate in the occurrence of ICP.4.In this study,RT-qPCR was used to study the expression of Nrf2 in placenta tissue of ICP patients from a genetic perspective.At present,no similar reports have been reported in China.5.There is a lack of relevant research in placenta of term pregnancy patients with severe ICP,which needs to be further studied in experimental animal models.