本文關鍵詞： 高血壓腦出血術后 通腑瀉熱活血湯 血漿代謝組學 氫譜核磁共振法 中醫(yī)藥　出處：《廣州中醫(yī)藥大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:從代謝組學角度研究高血壓腦出血術后痰瘀腑實證血清代謝物變化規(guī)律,尋找引起繼發(fā)性腦損害的相關病理標記物,探究其病理機制及研究通腑瀉熱活血湯促進高血壓腦出血術后痰瘀腑實證腦損害修復的可能機理,為拓展中醫(yī)藥的臨床應用提供實驗依據(jù)。方法:我們的研究納入自2015-7-1至2016-9-1月因高血壓腦出血而行手術治療的12名患者,采用氫譜核磁共振(1H-NMR)CPMG脈沖序列檢測這12名高血壓腦出血患者的術前、及術后第1、3、7、12天血漿樣本,每名患者采集5個血漿樣本,本實驗共收集60個血樣本,所有患者的術前、術后第1天、術后第3天、術后第7天、術后第12天各為1組,分為5組,所有患者術后第3天開始服用通腑瀉熱活血湯。對不同組之間代謝產物含量的變化,采用主成分分析(principal components analysis PCA)、偏最小二乘判別分析(PLS-Discriminant Analysis PLSDA),分析5組血漿的核磁共振波譜以及相應代謝物積分值的變化,篩選對實驗結果貢獻值最大的代謝物,采用自身前后對比,運用統(tǒng)計學配對t檢驗分析比較不同組間代謝物的變化,從代謝層面探討通腑瀉熱活血湯促進高血壓腦出血術后損傷修復的作用機制,并探討高血壓腦出血術后痰瘀腑實證的本質。結果:臨床實驗部分,經(jīng)氫譜核磁共振(1H-NMR)檢測,患者術前、術后第1天、術后第3天、術后第7天、術后第12天這5組血漿代謝譜存在明顯差異(P0.05),模式識別和主成份分析(PCA)顯示:高血壓腦出血術后第3天經(jīng)辨證為痰瘀腑實者,服用通腑瀉熱活血湯前后具有可區(qū)分性、可比較性;術前組和術后第1天組患者血漿中差異較大的特異性代謝物6個:丙氨酸、異亮氨酸、α-酮戊二酸、糖蛋白、前列腺素、極低密度脂蛋白。術后第1天組和術后第3天組中患者血漿中差異較大的特異性代謝物6個:γ-氨基丁酸、α-酮戊二酸、甜菜堿、絲氨酸、前列腺素E1、脂蛋白;術后第3天組和術后第12天組中患者血漿中差異較大的特異性代謝物6個:N-乙酰糖蛋白、α-葡糖糖、膽堿、肌醇、亮氨酸、谷氨酰胺。術后第7天組和術后第12天組中患者血漿中差異較大的特異性代謝物2個:N-乙酰糖蛋白、乳酸。結論:高血壓腦出血后,腦組織處于一種高能耗狀態(tài),糖異生、脂肪酸、三羧酸循環(huán)紊亂、免疫功能低下、興奮性氨基酸神經(jīng)毒害。當高血壓腦出血術后患者經(jīng)中醫(yī)辨證為痰瘀腑實證者,服用通腑瀉熱活血湯能改善腦出血后機體的的脂肪、糖代謝,減輕缺血缺氧損傷,穩(wěn)定細胞膜、維持細胞結構完整,促進已損傷細胞修復,最大限度恢復神經(jīng)細胞功能,改善預后。服用中藥后γ-氨基丁酸(GABA)的大量釋放可對抗谷氨酸等興奮性氨基酸的神經(jīng)毒性作用,完成對神經(jīng)元的保護,通腑瀉熱活血中藥能維持神經(jīng)元能量代謝穩(wěn)態(tài)及促進神經(jīng)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, 偽 -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: 緯 -aminobutyric acid, 偽 -ketoglutaric acid, betaine, serine, prostaglandin E1. Lipoprotein; The plasma specific metabolites of 6: N- acetylglycoprotein, 偽-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.
【學位授予單位】：廣州中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R651.12

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