The Expression Of Melatonin (MT), Nrf2, HO-1in The Pathogenesis Of Preeclampsia

Preeclampsia is pregnancy idiopathic disease, it is the main cause of the adverse outcome. The pathogenesis of this disease is unclear. Currently, there is Two-Stage theory. In the process of the development from the first stage to the second, the body needs to experience a series of pathophysiological changes, oxidative stress is the mainly factor, as a result of vascular endothelial damage. In preeclampsia, oxidative stress is important in the development of the frist stage to the second stage.Melatonin (melatonin, MT) is a kind of important indole neural endocrine hormone,it is an important antioxidant stress material, n-acetyl-5-methoxyl primary amines. It can directly eliminate free oxygen radicals and free nitrogen radicals. Some study found that Acute lung injury in vitro, cerebral ischemia reperfusion injury, renal injury caused by chemical drugs in animal models. MT resists the oxidative stress mainly through the Nrf2/ARE/HO-1pathways. There is MT expressed in peripheral blood of preeclampsia maternal which is significantly reduced compared with normal maternal, suggesting that MT may play an important effect on the changes of the pathogenesis of preeclampsia, however the specific mechanism and related pathways are unclear. Some studies have shown that Nrf2, HO-1expressed in the peripheral blood of preeclampsia puerpera have significant declineD. This study is proposed by measuring the expression level of MT, Nrf2, and HO-1in placental tissue of the preeclampsia maternal and the content of MT in peripheral blood, discussing the correlation of the three and their development of preeclampsia from the first stage to the second stage.Chapter I The expression of melatonin(MT) in placenta and peripheral blood of preeclampsiaObjective:Study the change of the melatonin levels between placenta and Peripheral Blood in puerpera with preeclampsia, and analyze the correlation between them. To explore the effects of melatonin for preeclampsia.Method:1.To choose singleton pregnancy pregnant women25cases who were diagnosed with preeclampsia and were admitted to accept delivery in Central South University Xiangya Second Hospital from July2013to March2014.10cases were mild preeclampsia group among them,15cases were severe preeclampsia group. At the same time, to choose the normal pregnant women15cases, and15women who were accepted the normal physical examination as control group.2.These selected outpatient drawn Peripheral venous blood when limosis,separated these serum and saved the specimen. All these selected hospitalized patients who were terminated pregnancy used cesarean delivery of lower uterine segment crosscutting.During the operation,we got the placental tissue in size of1cm3, and stored at-80℃in the refrigerator.3.To measure protein expression of melatonin in the placenta tissue with Western blot, measure protein expression of melatonin in peripheral venous blood with Elisa.Results:Elisa:MT level of the placental tissue was6.00±0.53pg/ml in Normal women, was59.38±2.19pg/ml in Normal control group, was38.43±1.50pg/ml in mild preeclampsia group, was24.84±2.58pg/ml in severe preeclampsia group. these four groups are statistically significant difference(P<0.05). Western blot:MT level of the placental tissue was0.37±0.04pg/ml in Normal control group, was0.26±0.04pg/ml in mild preeclampsia group, was0.09±0.03pg/ml in severe preeclampsia group, these three groups are statistically significant difference(P<0.05). Among normal puerperal、mild preeclampsia and severe preeclampsia, MT level in placenta tissue and peripheral blood was positive related. P=0.96.Conclusion:The levels of MT in peripheral venous blood have significant difference between pregnant women and normal women. This congclusion suggests that melatonin may have the function of protection in normal pregnancy. Compared with normal pregnant women, the melatonin level of the women who was suffered preeclampsia has stastisticlly significant difference, with the deterioration of the illness,the level of MT dwclined. The experiment leads that the lack of melatonin may be one of the reasons which reduced the capacity of oxidative stress resistance in eclampsia patients.The level of MT in placenta and peripheral blood was positive related between normal pregnancy and preeclampsia women. The results indicate that the peripheral blood melatonin may mainly be originated from the placenta.Chapter Ⅱ The expression of MT、HO-1and Nf2in placental tissue of preeclampsiaObjective:To study the expression of MT、HO-1and Nf2in placental tissue of preeclampsia pregnant women and the correlation of them, exploring their roles on the pathogenesis of preeclampsiaMethod:1.To choose singleton pregnancy pregnant women25cases who were diagnosed preeclampsia and were admitted to accept delivery in Central south university xiangya second hospital from July2013to March2014. Among them,10cases were mild preeclampsia group,15cases were severe preeclampsia group, and to choose the normal pregnant women15cases as control group.All these selected pregnant women who were terminated pregnancy used cesarean delivery of lower uterine segment crosscutting. During the operation, we got the placental tissue in size of1cm3,and stored at-80℃in the refrigerator.2.To measure protein expression of MT、Nrf2and HO-1in the placenta tissue with Western blot. Results:Nrf2level of the placental tissue was0.31±0.03in Normal control group, was0.18±0.06in mild preeclampsia group, was0.07±0.02in severe preeclampsia group.these three groups are statistically significant difference(P<0.05).HO-1level of the placental tissue was0.34±0.04in Normal control group, was0.19±0.04in mild preeclampsia group, was0.08±0.03in severe preeclampsia group.these three groups are statistically significant difference(P<0.05). Combined with the result of the experiment of the frist chapter, MT、Nrf and HO-1has positive correlation between placenta of normal maternal and preeclampsia group.But there are no obvious correlation among normal maternal and mild preeclampsia group and severe preeclampsia group.Conclusion:The expression of MT、Nrf2、HO-1in placental tissue of preeclampsia maternal have statistically significant difference, which suggests that melatonin play its antioxidant stress pathways in pregnancy through the pathways of the Nrf2/ARE/HO-1. The function of this pathway weakened, the pathological of preeclampsia changed.