维药异常黑胆质成熟剂抗抑郁症作用的血浆和尿液代谢组学研究

发布时间：2018-07-01 13:47

本文选题：异常黑胆质成熟剂 + 代谢组学　；参考：《新疆医科大学》2016年硕士论文

【摘要】：目的:观察异常黑胆质成熟剂(简称异黑成熟颗粒,ASMq)对抑郁症大鼠内源性代谢物变化的影响,从代谢组学角度探讨ASMq抗抑郁症作用的内在机制。方法:清洁级SD雄性大鼠,72只。采用慢性不可预见性温和应激(CUMs)诱导大鼠抑郁症模型。在模型建立后分别用低、中、高剂量(1.5,3.0,6.0g/kg)ASMq对抑郁症大鼠模型进行干预,并于第44 d处死大鼠,采用生物核磁共振技术检测血浆及尿液代谢物含量变化,分段积分后采用正交偏最小二乘判别(OPLS-DA)对1H-NMR谱数据进行模式识别分析。利用1H-NMR谱信息用PLS-DA分析可以把抑郁症模型组和ASMq低、中、高剂量组之间大鼠血浆代谢谱变化区分开,分析ASMq干预后抑郁症大鼠血浆和尿液中的内源性代谢物的变化。观察ASMq对抑郁症模型大鼠血浆和尿液代谢物的影响;结果:1.与正常对照组比较,抑郁症模型组大鼠血浆中异亮氨酸、乳酸、肌酸、谷氨酰胺、络氨酸、糖蛋白、脂类、不饱和脂类、β-羟丁酸、乙酸、丙氨酸、α-葡萄糖和β-葡萄糖等含量显著升高(P0.05),组氨酸的含量显著下降(P0.05),差异均有统计学意义。与抑郁症模型组比较,ASMq低、中、高剂量组大鼠血浆中组氨酸、α-葡萄糖、β-葡萄糖等含量显著升高(P0.05),肉毒碱、乳酸、β-羟丁酸、肌酸、丙酮酸、苯丙氨酸、丙氨酸、脂类(VLDL、LDL)、不饱和脂类、丙酮、络氨酸、糖蛋白和甲酸的含量显著下降(P0.05),差异有统计学意义。2.与正常对照组比较,抑郁症模型组大鼠尿液中乳酸、β-葡萄糖、不饱和脂类、酪氨酸、苯丙氨酸等含量显著升高(P0.05),异亮氨酸、β-羟丁酸、乙酰乙酸、丙酮酸、α-葡萄糖、肌酸的含量显著下降(P0.05),差异均有统计学意义。与抑郁症模型组比较,ASMq低、中、高剂量组大鼠尿液中脂类(VLDL)、异亮氨酸、缬氨酸、β-羟丁酸、亮氨酸、胆碱、糖蛋白、乙酰半胱氨酸、蛋氨酸、乙酰乙酸、丙酮酸、柠檬酸、谷氨酰胺、α-葡萄糖、β-葡萄糖、组氨酸、肌酸、酪氨酸、苯丙氨酸等含量显著升高(P0.05),乳酸、肉碱、氧化三甲胺(TMAO)、甘氨酸、不饱和脂类、甲酸的含量显著下降(P0.05),差异有统计学意义。结论:本研究优选的维药异常黑胆质成熟剂已有国药准字符合条件,ASMq可能通过对抑郁症大鼠的糖代谢,脂代谢,氨基酸代谢起到一定的调控和改善作用而提高机体兴奋性,治疗抑郁症。提示,调控抑郁症大鼠血浆和尿液代谢是ASMq抗抑郁症作用机制的主要方面。
[Abstract]:Aim: to observe the effect of abnormal black bile maturation granule (ASMq) on the changes of endogenous metabolites in depression rats, and to explore the mechanism of antidepressant effect of ASMq from the perspective of metabonomics. Methods: 72 SD male rats of clean grade were used. Chronic unpredictable mild stress (CUMs) was used to induce depression in rats. After the establishment of the model, low, middle and high doses of ASMq (1.5V 3.0g / kg) were used to interfere with the depression rat model, and the rats were killed on the 44th day. The contents of metabolites in plasma and urine were detected by biomagnetic resonance (BNMR). The 1H-NMR data were analyzed by orthogonal partial least squares discriminant (OPLS-DA) after piecewise integration. The changes of plasma metabolic spectrum in depression model group and low, medium and high dose groups could be distinguished by PLS-DA analysis, and the changes of endogenous metabolites in plasma and urine of depression rats after ASMq intervention could be analyzed. The effects of ASMq on plasma and urine metabolites in rats with depression were observed. Compared with the normal control group, the plasma levels of isoleucine, lactic acid, creatine, glutamine, complexine acid, glycoprotein, lipids, unsaturated lipids, 尾 -hydroxybutyric acid, acetic acid, 尾 -hydroxybutyric acid in the depression model group were higher than those in the normal control group. The contents of alanine, 伪 -glucose and 尾 -glucose increased significantly (P0.05), and the content of histidine decreased significantly (P0.05). Compared with the depression model group, ASMq was lower and higher in the high dose group than that in the depression model group (P0.05). The contents of carnitine, lactic acid, 尾 -hydroxybutyric acid, creatine, pyruvate, phenylalanine were significantly increased in the high dose group. The contents of lipid, unsaturated lipid, acetone, complex amino acid, glycoprotein and formic acid decreased significantly (P0.05), the difference was statistically significant. Compared with the normal control group, the contents of lactic acid, 尾 -glucose, unsaturated lipids, tyrosine, phenylalanine in the urine of the depression model group were significantly higher than those in the normal control group (P0.05), isoleucine, 尾 -hydroxybutyric acid, acetoacetic acid, pyruvate, 伪 -glucose, etc. Creatine content decreased significantly (P0.05), the differences were statistically significant. Compared with the depression model group, ASMq was lower and higher in the high dose group than that in the depression model group. The levels of lipids (VLDL), isoleucine, valine, 尾 -hydroxybutyric acid, leucine, choline, glycoprotein, acetylcysteine, methionine, acetoacetic acid, pyruvate, citric acid in the urine of rats were lower than those in the depression model group. The contents of glutamine, 伪 -glucose, 尾 -glucose, histidine, creatine, tyrosine and phenylalanine increased significantly (P0.05), and the contents of lactic acid, carnitine, trimethylamine oxide (TMAO), glycine, unsaturated lipid and formic acid decreased significantly (P0.05). Conclusion: ASMq can improve the excitability of rats with depression by regulating and improving the metabolism of glucose, lipid and amino acid. Treat depression. It is suggested that the regulation of plasma and urine metabolism is the main mechanism of ASMq antidepressant action.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R29

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