S-腺苷蛋氨酸对子宫平滑肌收缩及LPS诱导早产模型的影响

发布时间：2018-04-09 16:44

本文选题：S-腺苷蛋氨酸　切入点：蛋氨酸　出处：《浙江大学》2017年硕士论文

【摘要】：目的：探究S-腺苷蛋氨酸对子宫平滑肌收缩的影响,及在脂多糖(LPS)诱导的感染性早产中发挥的作用,为安全有效的新型保胎药物提供理论依据。方法：(1)ICR小鼠离体子宫平滑肌收缩实验：取未妊娠、妊娠早期(6.5d)、妊娠中期(12.5-13.5d)和妊娠晚期(16.5-17.5d)小鼠,将其脱颈椎处死,解剖子宫,在乐氏溶液中将其沿纵行肌纤维方向将子宫分为约0.5cm长。将所取肌条沿纵行肌纤维方向,两端分别固定于张力换能器,采用累积浓度给药法,给予沙丁胺醇、S-腺苷蛋氨酸、蛋氨酸、牛磺酸、精氨酸等药物,记录、测量并分析离体子宫收缩曲线。(2)LPS诱导的ICR小鼠早产模型建立以及各处理组早产率和仔鼠死亡率的统计：ICR雌雄小鼠交配,将孕鼠随机分为空白对照组,LPS实验对照组,LPS+氨基酸药物(S-腺苷蛋氨酸、蛋氨酸、牛磺酸和精氨酸)处理组,雌鼠怀孕14.5d时腹腔注射1000μg/kg剂量的LPS或者PBS 0.2ml作为溶剂对照,分别统计各处理组雌鼠早产率和仔鼠死亡率；收集产后小鼠子宫、宫颈样本,制备组织切片,HE染色,观察病理改变。结果：(1)沙丁胺醇和S-腺苷蛋氨酸对未孕、妊娠早期(6.5d)、妊娠中期(12.5-13.5d)和妊娠晚期(16.5-17.5d)四个时间点的小鼠离体子宫平滑肌的收缩均有较强的抑制作用,分别在10-7mol/L和1.0mmol/L的溶液浓度下完全抑制收缩。蛋氨酸、牛磺酸在实验浓度下对ICR小鼠离体子宫平滑肌的收缩影响不明显,而精氨酸有增强收缩的作用,同时不同阶段的子宫平滑肌敏感性不同。(2)在LPS的诱导下,ICR小鼠的早产率和仔鼠死亡率均达到100%,而30mg/kg剂量的S-腺苷蛋氨酸组和蛋氨酸组相比LPS组均有明显下降(早产率分别降至0和40%,仔鼠死亡率分别降至30.3%和41.7%)。牛磺酸和精氨酸对LPS诱导的早产率和仔鼠死亡率无明显作用。病理切片结果提示LPS组炎症细胞浸润明显,30mg/kg剂量的S-腺苷蛋氨酸组有明显减轻,但100mg/kg剂量的S-腺苷蛋氨酸组并没有明显改善,而蛋氨酸组炎症细胞浸润明显,提示低剂量S腺苷蛋氨酸对LPS诱导的早产具有一定保护作用。牛磺酸对LPS诱导的早产病理变化影响不明显,而精氨酸对炎症细胞浸润有一定抑制趋势。结论：在离体水平,证明了S-腺苷蛋氨酸能够有效抑制妊娠个阶段离体子宫的收缩,并在整体水平建立了LPS诱导的早产模型,证明了30mg/kg的S-腺苷蛋氨酸和蛋氨酸在降低早产率和仔鼠死亡率中作用明显,从而证明S-腺苷蛋氨酸可能是一个有效并且安全的保胎药。S-腺苷蛋氨酸在抑制离体子宫平滑肌收缩和LPS诱导的早产中的作用的具体机制有待进一步的研究。
[Abstract]:Aim: to investigate the effect of S-adenosylmethionine on the contraction of uterine smooth muscle and its role in lipopolysaccharide induced infectious premature delivery.The uterus was divided into about 0.5cm long along the direction of longitudinal muscle fiber in Le's solution.The muscle strips were fixed on the tension transducer at both ends along the longitudinal direction of muscle fibers. Salbutamol S-adenosine, methionine, taurine, arginine and other drugs were administrated by the method of cumulative concentration administration.The model of ICR mice induced by lipopolysaccharide (LPS) in vitro was measured and analyzed.Pregnant rats were randomly divided into control group (control group) and control group (control group) treated with L-adenosine, methionine, taurine and arginine. Female rats were injected intraperitoneally with 1000 渭 g/kg LPS or PBS 0.2ml as solvent control group at day 14.5 after pregnancy.The preterm delivery rate and the infant mortality rate of each treatment group were counted, the uterus and cervix samples of postpartum mice were collected, the tissue sections were prepared by HE staining, and the pathological changes were observed.Results: (1) Salbutamol and S-adenosylmethionine could inhibit the contraction of isolated uterine smooth muscle at four time points, I. e., pregnant women, early pregnancy (6.5d), middle pregnancy (12.5-13.5d) and late pregnancy (16.5-17.5d).The shrinkage was completely inhibited at the concentration of 10-7mol/L and 1.0mmol/L, respectively.Methionine and taurine had little effect on the contraction of isolated uterine smooth muscle of ICR mice at the experimental concentration, but arginine could enhance the contraction.At the same time, the sensitivity of uterine smooth muscle at different stages was different.) under the induction of LPS, the preterm delivery rate and the infant mortality of ICR mice reached 100. The 30mg/kg dose of S- adenosylmethionine group and methionine group were significantly lower than that of LPS group (early morning).The birth rate decreased to 0% and 40%, and the infant mortality rate decreased to 30.3% and 41.7%, respectively.Taurine and arginine had no effect on LPS induced premature delivery rate and infant mortality.The results of pathological section showed that the infiltration of inflammatory cells in LPS group was obviously reduced with 30 mg / kg of S- adenosylmethionine group, but that in 100mg/kg group was not significantly improved, while in methionine group, the infiltration of inflammatory cells was obvious.It suggested that low dose of S-adenosylmethionine could protect preterm labor induced by LPS to some extent.Taurine had no obvious effect on the pathological changes of LPS induced preterm labor, but arginine had a tendency to inhibit the infiltration of inflammatory cells.Conclusion: at the in vitro level, S- adenosylmethionine can effectively inhibit the contraction of isolated uterus during pregnancy, and establish the model of preterm delivery induced by LPS at the whole level.It was proved that 30mg/kg 's S-adenosylmethionine and methionine played a significant role in reducing premature delivery rate and infant mortality.It is suggested that S- adenosylmethionine may be an effective and safe antifetal drug. The mechanism of S- adenosylmethionine in inhibiting uterine smooth muscle contraction and LPS induced premature delivery needs further study.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R965

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