从代谢组学分析高血压脑出血术后继发性脑损害的病机及通腑泻热活血汤的作用机理

发布时间：2018-01-19 21:24

本文关键词： 高血压脑出血术后通腑泻热活血汤血浆代谢组学氢谱核磁共振法中医药　出处：《广州中医药大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:从代谢组学角度研究高血压脑出血术后痰瘀腑实证血清代谢物变化规律,寻找引起继发性脑损害的相关病理标记物,探究其病理机制及研究通腑泻热活血汤促进高血压脑出血术后痰瘀腑实证脑损害修复的可能机理,为拓展中医药的临床应用提供实验依据。方法:我们的研究纳入自2015-7-1至2016-9-1月因高血压脑出血而行手术治疗的12名患者,采用氢谱核磁共振(1H-NMR)CPMG脉冲序列检测这12名高血压脑出血患者的术前、及术后第1、3、7、12天血浆样本,每名患者采集5个血浆样本,本实验共收集60个血样本,所有患者的术前、术后第1天、术后第3天、术后第7天、术后第12天各为1组,分为5组,所有患者术后第3天开始服用通腑泻热活血汤。对不同组之间代谢产物含量的变化,采用主成分分析(principal components analysis PCA)、偏最小二乘判别分析(PLS-Discriminant Analysis PLSDA),分析5组血浆的核磁共振波谱以及相应代谢物积分值的变化,筛选对实验结果贡献值最大的代谢物,采用自身前后对比,运用统计学配对t检验分析比较不同组间代谢物的变化,从代谢层面探讨通腑泻热活血汤促进高血压脑出血术后损伤修复的作用机制,并探讨高血压脑出血术后痰瘀腑实证的本质。结果:临床实验部分,经氢谱核磁共振(1H-NMR)检测,患者术前、术后第1天、术后第3天、术后第7天、术后第12天这5组血浆代谢谱存在明显差异(P0.05),模式识别和主成份分析(PCA)显示:高血压脑出血术后第3天经辨证为痰瘀腑实者,服用通腑泻热活血汤前后具有可区分性、可比较性;术前组和术后第1天组患者血浆中差异较大的特异性代谢物6个:丙氨酸、异亮氨酸、α-酮戊二酸、糖蛋白、前列腺素、极低密度脂蛋白。术后第1天组和术后第3天组中患者血浆中差异较大的特异性代谢物6个:γ-氨基丁酸、α-酮戊二酸、甜菜碱、丝氨酸、前列腺素E1、脂蛋白;术后第3天组和术后第12天组中患者血浆中差异较大的特异性代谢物6个:N-乙酰糖蛋白、α-葡糖糖、胆碱、肌醇、亮氨酸、谷氨酰胺。术后第7天组和术后第12天组中患者血浆中差异较大的特异性代谢物2个:N-乙酰糖蛋白、乳酸。结论:高血压脑出血后,脑组织处于一种高能耗状态,糖异生、脂肪酸、三羧酸循环紊乱、免疫功能低下、兴奋性氨基酸神经毒害。当高血压脑出血术后患者经中医辨证为痰瘀腑实证者,服用通腑泻热活血汤能改善脑出血后机体的的脂肪、糖代谢,减轻缺血缺氧损伤,稳定细胞膜、维持细胞结构完整,促进已损伤细胞修复,最大限度恢复神经细胞功能,改善预后。服用中药后γ-氨基丁酸(GABA)的大量释放可对抗谷氨酸等兴奋性氨基酸的神经毒性作用,完成对神经元的保护,通腑泻热活血中药能维持神经元能量代谢稳态及促进神经元的生存。
[Abstract]:Objective: to study the changes of serum metabolites in post-operative phlegm-stasis syndrome of hypertensive intracerebral hemorrhage from the perspective of metabolomics, and to search for the related pathological markers to cause secondary brain damage. To explore its pathological mechanism and to study the possible mechanism of Tongfu Xierehuoxue decoction to promote the repair of phlegm and stasis syndrome brain damage after hypertensive intracerebral hemorrhage. Methods: our study included 12 patients who underwent surgical treatment for hypertensive intracerebral hemorrhage from 2015-7-1 to 2016-9-1. The plasma samples of 12 patients with hypertensive intracerebral hemorrhage were detected by 1H-NMR-CPMG pulse sequence before operation and 712 days after operation. A total of 60 blood samples were collected from each patient. All patients were divided into 5 groups before operation, 1 day after operation, 3 days after operation, 7 days after operation and 12 days after operation. All patients began to take Tongfu Xiexie Huoxue decoction on the third day after operation. Principal components analysis (PCA) was used. Partial least squares discriminant analysis (PLS-discriminant Analysis PLSDAA) was used to analyze the changes of plasma nuclear magnetic resonance (NMR) spectra and the corresponding metabolite integrals in 5 groups. The metabolites which contributed the most to the experimental results were screened and compared before and after the experiment. Statistical paired t test was used to analyze and compare the changes of metabolites between different groups. To explore the mechanism of Tongfu Xierehuoxue decoction (Tongfu Xierehuoxue decoction) in promoting the repair of injury after hypertensive intracerebral hemorrhage, and to explore the essence of phlegm and stasis after hypertensive intracerebral hemorrhage. Results: clinical experiment part. The results of 1H-NMRs showed that there were significant differences in plasma metabolic spectrum between the 5 groups before and after operation, 1 day after operation, 3 days after operation, 7 days after operation and 12 days after operation (P0.05). Pattern recognition and principal component analysis (PCAA) showed that the syndrome differentiation of phlegm and blood stasis in patients with hypertensive intracerebral hemorrhage on the 3rd day after operation was distinguishable and comparable before and after taking Tongfu Xierehuoxue decoction; There were 6 specific metabolites in plasma of patients before and after operation: alanine, isoleucine, 伪 -ketoglutaric acid, glycoprotein, prostaglandin. Very low density lipoprotein (VLDL). There were six specific metabolites in plasma of patients in the first day after operation and the third day after operation: 纬 -aminobutyric acid, 伪 -ketoglutaric acid, betaine, serine, prostaglandin E1. Lipoprotein; The plasma specific metabolites of 6: N- acetylglycoprotein, 伪-glucosamine, choline, inositol, leucine were significantly different between the third day group and the 12th day group. Glutamine. There were significant differences in plasma specific metabolites 2: N- acetyl glycoprotein and lactic acid between the 7th and 12th day after operation. Conclusion: after hypertensive intracerebral hemorrhage. Brain tissue is in a state of high energy consumption, glucose allogenesis, fatty acid, tricarboxylic acid circulation disorder, low immune function. Excitatory amino acid neurotoxicity. When patients with hypertensive intracerebral hemorrhage after the syndrome differentiation of phlegm and stasis, taking Tongfu Xierehuoxue decoction can improve the body after cerebral hemorrhage fat, sugar metabolism. Reduce ischemia and hypoxia injury, stabilize cell membrane, maintain the integrity of cell structure, promote the repair of damaged cells, and maximize the recovery of nerve cell function. The release of GABA can antagonize the neurotoxicity of glutamic acid and other excitatory amino acids and protect neurons. Chinese herbal medicine can maintain the steady state of neuronal energy metabolism and promote the survival of neurons.
【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R651.12

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