清热化痰汤治疗青年原发性高血压痰热壅盛证的疗效及代谢组学研究

【作者】 冯玄超；

【导师】 胡元会；

【作者基本信息】 北京中医药大学 ， 中医学， 2012， 硕士

【摘要】 目的：观察中药清热化痰汤治疗青年原发性高血压痰热壅盛证的临床疗效。同时基于磁共振氢谱(’H-NMR)代谢组学研究方法,结合主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA)方法,初步探究青年原发性高血压痰热壅盛证患者血清内源性代谢标志物,观察清热化痰汤对青年原发性高血压痰热壅盛证患者4周末血清内源性代谢标志物的影响。为原发性高血压痰热壅盛证的诊断以及中医药治疗提供客观依据。方法：选择2010年5月至2012年1月,中国中医科学院广安门医院心内科门诊就诊青年原发性高血压辨证为痰热壅盛证患者33例,采用清热化痰汤治疗4周。治疗期间观察每周患者血压及症状改善情况。从中选取12例男性高血压患者,在治疗前、治疗4周后晨起空腹抽取静脉血,同时随机选取本院体检正常的青年男性志愿者12名晨起空腹抽取静脉血。所有静脉血经低温高速离心机离心后留取血清,保存于-80℃冰箱中。在Bruker AVANCE III-500MHz超导傅立叶变化核磁共振波谱仪上,采用有预饱和的增强谱(NOESY)、弛豫时间编辑(CPMG)和扩散编辑(LED)脉冲序列,将所得积分值行主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA).观察青年原发性高血压痰热壅盛证患者血清内源性代谢产物,以及清热化痰汤干预后患者血清内源性代谢产物的变化。结果：1.清热化痰汤对血压的影响：患者血压在服药一周后就有下降,且收缩压与治疗前相比有差异(P<0.05),舒张压与治疗前相比有明显差异(P<0.01)。连续治疗4周后,降压疗效显示：显效23例,占69.69%；有效8例,占24.24%；总有效率为93.93%。无效2例。2.清热化痰汤对证候及症状的影响：患者服药一周后证候评分即有下降,并与疗前有差异(P<0.05)。连续治疗4周后,证候疗效显示：显效26例,占78.79%；有效5例,占15.14%；总有效率为93.93%。无效2例。且眩晕、头痛、头重如裹、气短、急躁易怒、胸闷、失眠等单一症状均有改善。3.青年原发性高血压痰热壅盛证患者和健康对照者血清中小分子及大分子化合物可利用代谢组学手段加以区分。得出了青年原发性高血压痰湿壅盛证的特异性血清内源性代谢物为：低密度/极低密度脂蛋白, N-乙酰糖蛋白,0-乙酰糖蛋白,脂类,不饱和脂肪酸,高密度脂蛋白,磷脂酰胆碱,胆碱磷酸,胆碱/磷酸胆碱,丙氨酸,乳酸,谷氨酸盐,葡萄糖,柠檬酸,3-羟基丁酸。4.青年原发性高血压痰热壅盛证患者服用清热化痰汤治疗4周后血清中小分子及大分子化合物可利用代谢组学手段与治疗前区分。从得分图上看,青年原发性高血压痰热壅盛证治疗后组介于青年原发性高血压痰热壅盛证治疗前组和健康对照组之间,进一步分析发现治疗后患者特异性血清内源性代谢物与治疗前相比有所改善。结论：1.临床上应用清热化痰汤治疗青年原发性高血压痰热壅盛证病人疗效显著：降压疗效显示总有效率为93.93%；证候积分疗效显示总有效率为93.93%。证明清热化痰汤可有效降低血压,改善症状。2.青年原发性高血压痰热壅盛证患者体内存在物质代谢紊乱的情况：糖类代谢紊乱表现在：血清中葡萄糖,乳酸,柠檬酸含量下降。脂类代谢紊乱表现在：血清中低密度/极低密度脂蛋白,脂类,不饱和脂肪酸含量升高；高密度脂蛋白,磷脂酰胆碱,胆碱/磷酸胆碱,胆碱磷酸,3-羟基丁酸含量下降。蛋白质代谢紊乱表现在：血清中丙氨酸,谷氨酸盐含量下降；N-乙酰糖蛋白,0-乙酰糖蛋白含量升高。3.清热化痰汤可有效改善青年原发性高血压痰热壅盛证患者代谢紊乱的情况,主要表现在：可适当升高血清中葡萄糖、乳酸、柠檬酸、高密度脂蛋白、磷脂酰胆碱、胆碱/磷酸胆碱、胆碱磷酸、3-羟基丁酸、丙氨酸、谷氨酸盐的含量,降低低密度/极低密度脂蛋白、脂类、不饱和脂肪酸、N-乙酰糖蛋白、0-乙酰糖蛋白的含量。更多还原

【Abstract】 Objective:To observe the curative effect of Chinese medicine Qing Re Hua Tan (QRHT) Tang in youth essential hypertension (YEH) patients with abundant phlegm-heat. And based on’H-NMR metabolomics, combining Principal Components Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA) to explore the serum endogenous biomarker substances of YEH patients with abundant phlegm-heat and observe the effect of QRHT Tang in those serum endogenous biomarker substances after4weeks treatment. Provide objective basis for diagnosis and TCM treatment of EH patients with abundant phlegm-heat syndrome.Methods:33selected cases all came from Guang’anmen Hospital, China Academy of Chinese Medical Sciences out-patients with YEH patients and differentiated by two associate chief physicians with abundant phlegm-heat syndrome. All the patients were treated by QRHT Tang for4weeks. During the treatment, patient measured his/her blood pressure three times a day and reported it to the doctor when he/she.came to hospital meanwhile the doctor asked the patient about the symptoms and finish the Case Report Form (CRF). Select12male YEH patients and12male healthy young people. All serum samples were detected by’H-NMR and research the differences of metabolites by PCA and PLS-DA.Results:1. Curative effect of QRHT Tang on blood pressure:blood pressure began to drop at the very first week. After continuous4weeks’treatment, there were23markedly effective cases and8effective cases; the total effective rate was93.93%.2. Curative effect of QRHT Tang on syndrome and symptoms:syndrome score began to drop at the very first week. After continuous4weeks’treatment, there were26markedly effective cases and5effective cases; the total effective rate was93.93%. QRHT Tang can improve symptoms.3. The serum substances of YEH patients with abundant phlegm-heat and the healthy people can be distinguished by’H-NMR metabolomics methods. The serum endogenous biomarker substances of YEII patients with abundant phlegm-heat are:LDL/VLDL, N-Ac, O-Ac, lipid, HDL, PtdCho, Lactate, Alanine, Cho/Pcho, GPC, Glucose,3-HB, Citrate, Glutamine.4. After4weeks’treatment, the serum substances can be distinguished between the YEH patients with abundant phlegm-heat and the healthy people. The serum endogenous biomarker substances tendered to the healthy people after the treatment.Conclusion:1. Chinese medicine QRHT Tang can effectively reduce the patient’s blood pressure and the symptoms score, improve the quality of life.2. There are metabolic disorders in YEH patients with abundant phlegm-heat. The content of Glueose, Lactate and Citrate in those patients are lower than health people shows the carbohydrate metabolism disorders. The content of LDL/VLDL, lipid and UFA in those patients are higher than health people, while the content of HDL, PtdCho, Cho/Pcho, GPC and3-HB in those patients are lower than health people shows the lipid metabolic disorders. The content of Alanine and Glutamine in those patients are lower than health people, while the content of N-Ac and O-Ac in those patients are higher than health people shows the proteometabolism disorders.3. Chinese medicine QRHT Tang can effectively change the metabolic disorders in YEH patients with abundant phlegm-heat. QRHT tang can appropriately increase the content of Glueose, Lactate, Citrate, HDL, PtdCho, Cho/Pcho, GPC,3-HB, Alanine and Glutamine. It also can appropriately decrease the content of LDL/VLDL, lipid, UFA, N-Ac and O-Ac. Provide objective basis for its curative effect.更多还原