The Effect Of Hydrogen Sulfide On The Expressions Of Contraction-associated Proteins In Myometrial Cells And Its Underlying Mechanism

The gestational age greater than 28 weeks while less than 37 weeks due to various reasons advanced into labor are regarded as premature,which is one of the most common pathological disease during pregnancy,and is a leading cause of neonatal death.Currently,although the medical technology progresses rapidly and the medical levels have been significantly improved,many premature births have been prolonged after timely treatments and extended their gestational ages,the treatment strategies in numerous premature infants are still unavailable,leading to many adverse pregnancies.According to the WHO reports,it is indicated that the incidence of preterm delivery is as high as 9.6%worldwide,and more than 1 million a year of perinatal death due to premature birth.In addition,more and more infants suffer from diseases due to preterm birth,which cause serious burdens on their families and our society.The possible reason could be that the mechanism of myometrial cells from the resting state to activate state has not been clarified.We have no effective method and intervention strategies to restrain myometrium‘s contractions to prevent and treatment the preterm labor.Therefore,the study on the mechanism of premature is urgently all over the world.Previous studies have already demonstrated that human myometrium from resting state changing into contraction need to express a serious of contraction-associated proteins?CAPs?,such as junction proteins,oxytocin receptors and prostaglandins receptors?PGR?,etc.More and more studies have pointed that the delivery may be an inflammatory response process.Study conducted in 1980 has already pointed the uterine local cytokines and chemokines may participate in the process of childbirth.Further more,many studies have also founded that the cytokines and chemokines of womb increased significantly in both preterm and term labor.At the process of labor,all of myometrium,cervix and decidual tissues have inflammatory reactions obviously,which including the rise levels of oedema,neutrophil infiltration,and the increased of inflammatory cytokines,chemokines and prostaglandins.However,in previous studies the mechanism is still unclear.Hydrogen sulfide as the third type of gas signal molecule founded in recent years,is involved in many physiological and pathological changes in the body systems.Recently,some studies have founded there were many endogenous hydrogen sulfide synthetases in myometrium,prompted that uterine has the abilities to synthesize the endogenous hydrogen sulfide.Several other studies also have found that low dose of hydrogen sulfide could inhibit myometrial contractions,maintain the uterus steadily and keep the myometrium in a resting state.However,these mechanisms remain to be further studied.Our study's aim is to explore the inhibition mechanisms of myometrium contraction by hydrogen sulfide through evaluated the levels of myometrial contraction-associated proteins and the pro-inflammatory factors.By means of this reach we may provide a new idea for prevention and treatment of the premature delivery.Because of the delivery mechanism of preterm labor and normal pregnancy is the same,and the premature cases are too little to collect samples,so in this subject we collected the normal full-term pregnancy myometrial tissues as the research objects.At first,we confirmed that there were differences of the expressions on CAPs and the pro-inflammatory cytokines between the myometriums of labor and non-labor.Then we analysised the correlations of these proteins,prompted that there were higher expressions of CAPs and pro-inflammatory factors than control group's,and significant correlates between those proteins.After this,we puted donor sodium hydrosulfide which can produce hydrogen sulfide in the original generation of human normal myometriums,still detected the expressions of the myometrium CAPs and pro-inflammatory factors,found that H₂S had a negative role in the regulation of those proteins.Then,we added pro-inflammatory cytokines IL-1?in the medium,founded that the inhibitory effect of H₂S on CAPs had reversed.It was further confirmed that the productions of the myometrium CAPs might be associated with the pro-inflammatory cytokines,which might be the intermediate links.Finally,we found that K_ATP channel blocker could inhibite the negative expressions of H₂S on pro-inflammatory cytokines.It suggested that these above changes might be achieved through the K_ATP channels.Conclusion:There is a high expression of CAPs and pro-inflammatory in human myometriums in the condition of labor;H₂S suppresses the expression of CAPs via inhibition of pro-inflammatory cytokines in human myometrium.The inhibitory effect of H₂S on pro-inflammatory cytokines is dependent on activation of K_ATP channels.