The Effect Of S-adenosylmethionine On The Contraction Of Uterine Smooth Muscle And LPS-induced Preterm Labor

Objective:To investigate the effect of S-adenosylmethionine (SAMe) on contraction of uterine smooth muscle and its role in preterm labor induced by LPS, and to provide a theoretical basis for novel drug for preterm labor with good characters in safety and effectiveness.Methods:(1) In vitro experiments-contraction of isolated uterine smooth muscle of ICR mice: The mice were sacrificed from non-pregnat mice, and pregnancy early (6.5 days), mid pregnancy (12.5 to 13.5 days) and late pregnancy (16.5 to 17.5 days). The uterus was dissected from the different time-points pregnant mice, and the uterus was divided into about 0.5 cm length in the direction of the longitudinal muscle fibers in the Lock's solution. The muscle strips were taken along the longitudinal direction of the muscle fibers and fixed to the transducers at both ends. Sulbactamol, SAMe, methionine, taurine, arginine and other drugs were administered by the cumulative concentration administration method, the uterine contraction curves were recorded, measured and analyzed. (2) In vivo experiments -- LPS-induced premature mouse model was established and the premature delivery rate and the mortality rate of the offspring were recorded:ICR pregnant mice were randomly divided into blank control group, LPS control group, LPS+SAMe, LPS+methionine, LPS+taurine and LPS+arginine group. The female mice were injected intraperitoneally with 1000?g/kg LPS or 0.2ml PBS as the solvent control at 14.5d after pregnancy. Premature delivery and the mortality or survival offspring were recorded; Uterus and cervix were collected further study.RESULTS:(1) The strong inhibitory effects of salbutamol and SAMe on contraction of isolated uterine smooth muscle of the mice in the early stage (6.5 days), the second trimester (12.5?13.5 days) and the third trimester (16.5?17.5 days) were observed, salbutamol 10-7mol/L and SAMe 1.0mmol/L completely inhibited contraction. The effects of the other three amino acids (methionine and taurine) on the contraction of isolated uterine smooth muscle in mice were not significant, while arginine can enhance the contraction of isolated uterine smooth muscle with different degree dependent on the different phase of pregnancy.(2) In the LPS-induced preterm mice model, the preterm birth rate and the mortality of the offspring were 100%, while in 30mg/kg SAMe group and the methionine group, they were significantly lower than the LPS group. The mortality rates were reduced to 30% and 41.7%, respectively. Taurine and arginine had no significant effect on LPS-induced premature delivery and mortality. Uterine tissues of maternal mice were harvested during there parturition and were then made into paraffin sections. Through HE staining, percentages of neutrophils in the myometria of each group were evaluated respectively.CONCLUSIONS:SAMe can effectively inhibit the contraction of uterine phases of pregnancy, and SAMe and methionine at 30 mg/kg can improve LPS-induced preterm labor and mortality of offspring. So SAMe may be a novel relaxation drug for uterine smooth muscle. The specific mechanism of SAMe in inhibiting the contraction of isolated uterine smooth muscle and mediating LPS-induced premature delivery remains to be further studied.