甲硫氨酸负荷致同型半胱氨酸轻度升高对大鼠肝脏脂质代谢的影响及机制研究

发布时间：2018-05-30 23:18

本文选题：甲硫氨酸 + 同型半胱氨酸　；参考：《上海交通大学学报(医学版)》2015年07期

【摘要】：目的了解高甲硫氨酸摄入对肝脏脂质代谢的影响及可能机制。方法选取6周龄健康SD雄性大鼠20只,随机分为对照组和甲硫氨酸负荷组。适应性喂养2周后,对照组饲以正常饮食并采用PBS灌胃,甲硫氨酸负荷组在正常饮食基础上采用甲硫氨酸灌胃,持续喂养8周,每周称取体质量,处死后收集血液和肝脏组织。肝脏称重并计算脏器系数;肝组织切片H-E染色进行组织学观察;血生化分析仪测定血清生化指标;采用ELISA法测定血清同型半胱氨酸水平;real-time PCR检测大鼠肝组织脂代谢相关酶基因的表达水平。在体外培养的Hep G2细胞,油红O染色光学显微镜观察甲硫氨酸负荷或同型半胱氨酸处理对细胞中脂质沉积的影响,Western blotting检测同型半胱氨酸处理后细胞中成熟型肝组织甾醇调节元件结合蛋白1c(n-SREBP1c)表达的变化。结果甲硫氨酸负荷组与对照组大鼠体质量的增长无明显差异,但甲硫氨酸负荷组的脏器系数显著高于对照组(P0.05);甲硫氨酸负荷组大鼠肝脏出现轻微小泡性脂肪变性,但未出现炎症和明显肝功能损害;甲硫氨酸负荷组大鼠血清同型半胱氨酸、血清总胆固醇及高密度脂蛋白水平显著高于对照组(P0.05);甲硫氨酸负荷组肝组织Fas、Acc、Scd1、Cpt1αmRNA表达与对照组比较差异无统计学意义(P0.05)。在甲硫氨酸或同型半胱氨酸作用下,Hep G2细胞发生明显的脂质蓄积;同型半胱氨酸处理Hep G2细胞n-SREBP1c表达显著增高。结论甲硫氨酸摄入过量将导致肝脏轻微脂肪变性,且与血液中同型半胱氨酸水平升高有关。甲硫氨酸负荷导致的同型半胱氨酸水平轻度升高可通过调节肝细胞脂质代谢关键转录因子的活化,对肝脏脂质代谢造成影响。
[Abstract]:Objective to investigate the effect of high methionine intake on liver lipid metabolism and its possible mechanism. Methods Twenty male SD rats aged 6 weeks were randomly divided into control group and methionine loading group. After 2 weeks of adaptive feeding, the control group was fed with normal diet and fed with PBS, and the methionine loaded group was fed with methionine on the basis of normal diet. The rats were continuously fed with methionine for 8 weeks. The body weight was taken out every week, and the blood and liver tissues were collected after death. The liver was weighed and the organ coefficient was calculated; H-E staining of liver sections was performed for histological observation; serum biochemical indexes were measured by blood biochemistry analyzer; Serum homocysteine level was measured by ELISA method and real-time PCR was used to detect the expression of lipid metabolism-related enzymes in rat liver tissue. Hep G2 cells cultured in vitro, Effects of methionine loading or homocysteine treatment on lipid deposition in cells were observed by oil red O staining optical microscope. The expression of sterol regulatory element binding protein 1cnSREBP1c in mature liver tissue was detected by Western blotting after homocysteine treatment. Results there was no significant difference in the growth of body mass between the methionine loading group and the control group, but the organ coefficient of the methionine loading group was significantly higher than that of the control group (P 0.05), and the slight vesicular steatosis appeared in the liver of the methionine loading group. However, there was no inflammation and obvious liver function damage, and the serum homocysteine level in methionine loading group was higher than that in the control group. The levels of serum total cholesterol and high density lipoprotein were significantly higher than those of the control group (P 0.05), and the expression of Cpt1 伪 mRNA in the liver tissue of the methionine loading group was not significantly different from that of the control group (P 0.05). Under the action of methionine or homocysteine, the lipid accumulation in Hep G2 cells was obvious, and the n-SREBP1c expression in Hep G2 cells treated with homocysteine was significantly increased. Conclusion excessive intake of methionine may lead to mild steatosis of the liver and may be associated with increased homocysteine levels in the blood. The slight increase of homocysteine level induced by methionine load may affect hepatic lipid metabolism by regulating the activation of key transcription factors of lipid metabolism in hepatocytes.
【作者单位】：重庆医科大学公共卫生与管理学院医学与社会研究中心健康领域社会风险预测治理协同创新中心;重庆医科大学附属第一医院糖脂代谢中心;
【分类号】：R575

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