The Relationship Between Uterine Artery Incision And Onset Of Preeclampsia In The Second Trimester Of Pregnancy And The Association Between H₂S Generating Enzymes And The Production Of Angiogenic Factors In Preeclamptic Placenta

Preeclampsia?PE?is a serious pregnancy-specific disease,the incidence rate of 3%-5%,with a wide range of parental endothelial dysfunction is characterized by its main clinical symptoms of 20 weeks after pregnancy,new blood pressure and protein Pee.The pathogenesis of the disease has not yet fully elucidated,and no clear diagnosis mechanism and effective treatment.Therefore,Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality and preterm birth is the world's leading cause of neonatal morbidity and mortality.Lacking of the predictive experiments and the typical clinical manifestations and laboratory tests,preeclampsia contribute to potential adverse maternal and neonatal outcomes.With the further development of preeclampsia pathogenesis,in the clinical diagnosis and treatment to provide a new means of inspection at the same time also put forward new requirements.At present,many of the pre-eclampsia predisposing indicators of the gradual increase,which,due to its noninvasive and easy to clinical characteristics of the development of a lot of attention.In view of placental perfusion insufficiency in the pathogenesis of preeclampsia plays a decisive role in the monitoring of uterine artery blood flow during pregnancy by ultrasound,so the evaluation of placental perfusion to predict the development of preeclampsia potential development point.Many studies have suggested that pulsation index?PI?and resistance index?RI?of uterine arterial blood flow have a certain value in predicting the development of preeclampsia,but because of the fluctuation of different gestational age When to detect the maximum value of the forecast and did not reach a consensus.We try to find the correlation between uterine artery remodeling and risk of preeclampsia and vascular endothelial injury in the second trimester of pregnancy?22-24 weeks of gestation?.Up to now,The only known cure is delivery of the placenta,which also prompted us placenta principle contributor to the pathogenesis of preeclampsia.In recent years,many studies have found that serum levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase 1?sFlt-1?and soluble endoglin?sEng?in preeclampsia patients significantly higher than normal ones,and the placenta is the main organ that produces these anti-angiogenic factors,suggesting that the abnormal levels of anti-angiogenic factors produced by our placenta are closely related to the development of preeclampsia.Hematopoiesis,glomerular endothelial cell proliferation,HELLP?hemolysis,elevated liver enzymes,and low platelet?syndromes and brain edema and a series of preeclampsia and eclampsia clinical manifestations.Therefore,it is very important to explore the regulatory mechanism of the production of anti-angiogenic factors in the placenta.Hydrogen sulfide?H₂S?is a gas signal transduction factor found in recent years,involved in the body of a variety of physiological and pathological processes such as relaxation of blood vessels,heart protection,inflammatory response.Endogenous H₂S is a related metabolite of the methionine cycle in vivo.Methionine is produced by cystathionine?--lyase?CSE?can produce H₂S.Studies have shown that CBS and CSE are widely expressed in placenta of normal pregnancy,but the expression of these two enzymes is significantly reduced in the placenta of patients with preeclampsia.This suggests that a reduction in H₂S production in the placenta that reduces CBS and CSE expression may lead to preeclampsia.So,what is the reduction in H₂S through what mechanisms lead to the occurrence of preeclampsia,whether by regulating the expression of anti-angiogenic factors leading to disease,these problems have not yet elucidated.Although many studies have confirmed that sFlt-1 plays an important role in the pathogenesis of preeclampsia,its mechanism has not yet been fully elucidated.Since the soluble protein is mainly cut through the membrane-bound form,the enzymatic hydrolysis of the integrin-like metalloproteinase family?ADAMs?can mediate the shedding of the protein.We speculate that the ADMAs family may have a role in sFlt-1 regulation.The main results are as follows:Part 1:The relationship between uterine artery incision and onset of preeclampsia in the second trimester of pregnancy2800 cases of singleton primiparas who received antenatal examination in Maternal and Child Health Hospital of Pudong New Area Shanghai between April 2014 and October2015 were selected for prospective study and divided into notch group and non-notch group according to the uterine artery notch at 22-24 weeks of gestation,serum was collected at 24-30 weeks,31-36 weeks and 37-41 weeks of gestation respectively to determine sFlt-1 and sEng in serum,ultrasonography was conducted to determine uterine spiral arterial resistance index?RI?and pulsatility index?PI?.We found that the incidence of preeclampsia in the uterine artery is significantly higher than that in the normal group,and the second trimester placental perfusion index?PI,RI?was statistically significant.The levels of serum sFlt-1 and sEng were significantly increased in different gestational weeks.Part 2:The association between H₂S generating enzymes and the production of angiogenic factors in preeclamptic placenta1.The expression of H₂S-producing enzyme CBS and CSE in placenta ofpreeclampsia was lower than that in normal maternal placentaWe collected the clinical samples of Pudong Maternal and Child Health Hospital.Immunohistochemistry showed that the expression of CBS and CSE in placenta of preeclampsia was significantly lower than that in normal placenta.At the same time,western blot analysis showed that the expression of CBS CSE protein in placenta of preeclampsia group was significantly decreased.These results suggest that we reduce the expression of CBS CSE due to a decrease in the expression of CBS CSE in preeclampsia.2.H₂S can inhibit the formation of antiangiogenic factor sFlt-1 in the placentaWe take the Pudong Maternal and Child Health Hospital placenta clinical samples,the placenta in vitro tissue block culture.We used H₂S donor NaHS and CBS,CSE substrate L-cysteine for 48 h after treatment,collection of tissue culture supernatant,Elisa method found that both drugs can be dose-dependent reduction of anti-angiogenic factors The generation of sFlt-1.These results also suggest that H₂S can inhibit the production of antiangiogenic factor sFlt-1 in placental tissue.3.H₂S can inhibit the expression of ADAM17 in the placenta and inhibit theproduction of anti-angiogenic factor sFlt-1We take the Pudong Maternal and Child Health Hospital placenta clinical samples,the placenta in vitro tissue block culture.We used H₂S donor NaHS and CBS,CSE substrate l cysteine for 48h after the collection of tissue tissue,westernblot method found that both drugs can be dose-dependent reduction of ADAM17 protein expression.At the same time,we also cultivate the primary trophoblast cells,using siRNA knocking low ADAM17 protein expression,after the detection of cell supernatant in the expression of sFlt-1 also decreased.These results suggest that H₂S can inhibit the expression of ADAM17 in the placenta and inhibit the production of anti-angiogenic factor sFlt-1.Conclusion The decrease of expression of CBS and CSE in the placenta leads to the decrease of H₂S production,which leads to the increase of the expression of ADAM17 and the increase of the secretion of anti-angiogenic factor sFlt-1,which leads to the damage of vascular endothelium,leading to the occurrence and development of preeclampsia.