本文選題：S-腺苷蛋氨酸　切入點：蛋氨酸　出處：《浙江大學(xué)》2017年碩士論文

【摘要】：目的：探究S-腺苷蛋氨酸對子宮平滑肌收縮的影響,及在脂多糖(LPS)誘導(dǎo)的感染性早產(chǎn)中發(fā)揮的作用,為安全有效的新型保胎藥物提供理論依據(jù)。方法：(1)ICR小鼠離體子宮平滑肌收縮實驗：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,將其脫頸椎處死,解剖子宮,在樂氏溶液中將其沿縱行肌纖維方向?qū)⒆訉m分為約0.5cm長。將所取肌條沿縱行肌纖維方向,兩端分別固定于張力換能器,采用累積濃度給藥法,給予沙丁胺醇、S-腺苷蛋氨酸、蛋氨酸、牛磺酸、精氨酸等藥物,記錄、測量并分析離體子宮收縮曲線。(2)LPS誘導(dǎo)的ICR小鼠早產(chǎn)模型建立以及各處理組早產(chǎn)率和仔鼠死亡率的統(tǒng)計：ICR雌雄小鼠交配,將孕鼠隨機分為空白對照組,LPS實驗對照組,LPS+氨基酸藥物(S-腺苷蛋氨酸、蛋氨酸、�；撬岷途彼�)處理組,雌鼠懷孕14.5d時腹腔注射1000μg/kg劑量的LPS或者PBS 0.2ml作為溶劑對照,分別統(tǒng)計各處理組雌鼠早產(chǎn)率和仔鼠死亡率；收集產(chǎn)后小鼠子宮、宮頸樣本,制備組織切片,HE染色,觀察病理改變。結(jié)果：(1)沙丁胺醇和S-腺苷蛋氨酸對未孕、妊娠早期(6.5d)、妊娠中期(12.5-13.5d)和妊娠晚期(16.5-17.5d)四個時間點的小鼠離體子宮平滑肌的收縮均有較強的抑制作用,分別在10-7mol/L和1.0mmol/L的溶液濃度下完全抑制收縮。蛋氨酸、�；撬嵩趯嶒灊舛认聦CR小鼠離體子宮平滑肌的收縮影響不明顯,而精氨酸有增強收縮的作用,同時不同階段的子宮平滑肌敏感性不同。(2)在LPS的誘導(dǎo)下,ICR小鼠的早產(chǎn)率和仔鼠死亡率均達(dá)到100%,而30mg/kg劑量的S-腺苷蛋氨酸組和蛋氨酸組相比LPS組均有明顯下降(早產(chǎn)率分別降至0和40%,仔鼠死亡率分別降至30.3%和41.7%)。�；撬岷途彼釋PS誘導(dǎo)的早產(chǎn)率和仔鼠死亡率無明顯作用。病理切片結(jié)果提示LPS組炎癥細(xì)胞浸潤明顯,30mg/kg劑量的S-腺苷蛋氨酸組有明顯減輕,但100mg/kg劑量的S-腺苷蛋氨酸組并沒有明顯改善,而蛋氨酸組炎癥細(xì)胞浸潤明顯,提示低劑量S腺苷蛋氨酸對LPS誘導(dǎo)的早產(chǎn)具有一定保護(hù)作用。�；撬釋PS誘導(dǎo)的早產(chǎn)病理變化影響不明顯,而精氨酸對炎癥細(xì)胞浸潤有一定抑制趨勢。結(jié)論：在離體水平,證明了S-腺苷蛋氨酸能夠有效抑制妊娠個階段離體子宮的收縮,并在整體水平建立了LPS誘導(dǎo)的早產(chǎn)模型,證明了30mg/kg的S-腺苷蛋氨酸和蛋氨酸在降低早產(chǎn)率和仔鼠死亡率中作用明顯,從而證明S-腺苷蛋氨酸可能是一個有效并且安全的保胎藥。S-腺苷蛋氨酸在抑制離體子宮平滑肌收縮和LPS誘導(dǎo)的早產(chǎn)中的作用的具體機制有待進(jìn)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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R965

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