Investigation On Relationship Between New Gaseous Transmitter Hydrogen Sulfide And Preeclampsia

Preeclampsia is the leading cause of maternal and neonatal morbidity and mortality,which serious harms maternal and neonatal safety.Various hypotheses as to the origin of preeclampsia have been explored over time,but its pathogenesis is still unclear.It is well recognized that the main pathogenesis of preeclampsia is vascular endothelial activation,dysfunction and structural injury.Vascular endothelial cell injury caused by the imbalance of secretion vasoactive substances as well as its activity changes has played an important role in the process of preeclampsia development.Vascular contraction may be regulated by vasoactive substances such as NO,ET and prostaglandin.Their quantity and activity changing may lead to fetal placental vascular spasm,activation of coagulation system,placental perfusion cycle and systemic small artery spasm,which is the key that pathological changes of preeclampsia proliferated from placenta to systemic.Hydrogen sulfide(H₂S) is well known as a toxic gas with the characteristic smell of rotten eggs.But it is becoming increasingly clear that mammalian also produce H₂S.However,recent data have revealed that endogenous.H₂S is synthesized naturally in the body from L-cysteine mainly by the activity of two enzymes,cystathionineβ-synthase(CBS) and cystathionineγ-lyase(CSE).CBS seems to be main H₂S-forming enzyme in the brain and nervous system,where as CSE is the main H₂S-synthesizing enzyme in the cardiovascular system.In cardiovascular system,H₂S can relax smooth muscle cells by activating ATP-dependent K⁺ channels(K_ATP) and decrease the blood pressure.The deficit of H₂S/CSE system may be responsible for the development of spontaneous hypertension.The administration of exogenous H₂S can effectively prevent myocardial ischemia injury.The endogenous metabolism and physiological functions of H₂S position this gas well in the novel family of gas transmitters together with nitric oxide(NO) and carbon monoxide(CO).Now that H₂S can regulate the smooth muscle of blood tube,and NO as gaseous transmitter was closely related to the incidence of preeclampsia.So can we come to the conclusion whether the association does exist between H₂S and the incidence of preeclampsia?In order to study what a role can gaseous transmitter hydrogen sulfide do to the incidence of preeclampsia,we have had the following research:The distribution of CSE or CBS at normal full-term pregnancy and preeclampsia placenta;the Change and significance of H₂S/CSE system or H₂S/CBS system in the pathogenesis of preeclampsia;regulation of diastolic function of H₂S on human umbilical artery vascular smooth muscle.MethodsAll placenta and umbilical artery specimens were obtained from 26 preeclampsia maternal and 26 term healthy pregnancies after cesarean section or vaginal delivery.1.Using iramunohistochemistry to detect the distribution of CSE or CBS at controls and preeclampsia placenta;2.Using sensitive sulphur electrode to detect the activity of CBS at placenta of controls and preeclampsia;Using realtimePCR to detect the level of CBSmRNA at controls and preeclampsia placenta;3.Using umbilical artery in vitro vascular ring tension experiment to detect relaxing effect of exogenous H₂S on the human umbilical artery vascular smooth muscle and related mechanisms.Results1.CBS were distributed at controls and preeclampsia placenta;2.1)The activity of CBS at preeclampsia placenta was lower than the controls:2) The activity of CBS at preeclampsia placenta with the systolic blood pressure/diastolic blood pressure was a negative correlation;3) Compared with the controls,the level of CBSmRNA at the preeclampsia placenta has decreased;3.1)The diastolic response of preeclampsia's HUA induced by exogenous H₂S was lower than the controls.2)The diastolic response induced by exogenous H₂S has decreased after the intervention by glibenclamide.3) The diastolic response induced by exogenous H₂S has increased after the intervention by SNP.4) The diastolic response induced by exogenous H₂S has decreased after the intervention by L-NAME.Conclusion1.Endogenous H₂S may be synthesized at the placenta by CBS and play an important role in the pregnancy.2.The level of endogenous H₂S decline could be related to the incidence of preeclampsia.CBS activity is leading to possible downward adjustment of endogenous H₂S level of the reasons for the decline.Gene level of CBS were consistent downward trend also confirming this conclusion.3.Vasoconstrictor substances had increased the vascular reactivity of umbilical artery under the preeclampsia and vasorelaxant substances had decreased it;Exogenous H₂S can induce an acute vasorelaxing effect on human umbilical artery,which may be synergized by NO;H₂S vasorelaxing effect may partially inhibited by Glibenclamide,L-NAME.And Removal of vascular endothelial.It is suggested that H₂S vasorelaxing effect be related to activating K_ATPand promoting synthesis of NO in endothelial cell.