高血压病中医证型及药物干预的代谢组学研究
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摘要
目的：观察高血压病肝火亢盛证、痰湿壅盛证的代谢组学特点,比较两组证型间代谢组学物质差异,探析两证型潜在的判别生物标志物群。同时,观察高血压病治疗后代谢组学变化情况,探析降压药物对代谢谱的影响。
方法：在江苏省中医院心内科门诊及体检中心前来就诊与体检人群中,选取原发性高血压患者,其中符合病例入选标准的肝火亢盛证型患者10例(a组),痰湿壅盛证患者10例(b组),健康对照组人群15例(K组)。观察入组人群的生命体征及相关生化指标,并抽取受试者空腹12小时静脉血,对其中a、b组20例患者中的10人进行了降压药物干预,4周后取得空腹12小时静脉血,作为治疗后组(y组)。经样品前处理后,用GC/TOF-MS(气相色谱飞行时间质谱)技术对两证型组患者、健康人群、治疗后组的血清进行全谱代谢组学分析。运用代谢组学方法及基本统计学方法对血样结果进行分析,根据各样本的主成分得分作图,判别其组间差异,得出相关生物标志物群。
结果：(1)痰湿壅盛组患者的BMI、TG、·HDL-C、LDL-C与健康人群对照组间出现了明显差异(P<0.05),存在统计学意义。(2)肝火亢盛组、痰湿壅盛组与健康人群对照组间,代谢谱存在明显差异。(3)肝火亢盛组与痰湿壅盛组之间的代谢谱亦存在一定差异,两组间有显著性差异的化合物为苯丙氨酸、谷氨酸(P<0.05)。(4)药物干预后,患者血清代谢谱出现明显的变化,有显著差异的化合物如：果糖、苯丙氨酸、亚油酸(P<0.05)。
结论：(1)运用代谢组学的研究方法可以成功区分高血压病肝火亢盛组、痰湿壅盛组和正常对照组。(2)初步认为苯丙氨酸、谷氨酸可作为鉴别肝火亢盛证组与痰湿壅盛证组的代谢组学生物标志物。(3)初步得出受降压药物影响较为显著的代谢物质如：果糖、苯丙氨酸、亚油酸。(4)认为超重、肥胖、血脂异常与高血压病痰湿壅盛证的发生存在相关性。
Objective: Observed the metabonomics features on hyperactivity of liver fire syndrome and dampness and phlegm syndrome of essential hypertension. Metabolites were compared between two syndrome for seeking the potential biomarkers. Meanwhile,observed the changes in metabolomics after treatment of hypertension and the effect of antihypertensive drugs on the metabolism of spectrum.
Methods:This study selects patients with essential hypertension as subject, among which 10 patients with hyperactivity of liver fire syndrome as Group a,10 cases of dampness and phlegm syndrome as Group B and 15 health comparison cases as Group K. The selection is made under the Case Selection Criteria. The participants are chosen from Department of Cardiology in Jiangsu Provincial Hospital of TCM and the physical examination center. The vital sign and biochemical parameters of each groups of participants are observed; 12 hours of fasting venous blood was collected; 10 of 20 patients among Group a & b are taken antihypertensive medical for 4 weeks before obtain 24 hours of fasting venous blood. Thus these 10 patients are arranged in a new group (Group y). After the proper treatment of samples, a wide spectrum of plasma metabonomics analysis is organized on the blood sample of patients with two syndromes, healthy people and people in treatment. Using basic statistical methods and metabolomics approach to analyze the results of the blood sample.According to the principal component score plot of samples, can distinguish differences between groups and related biological markers can be obtained.
Results:(1) Dampness and phlegm syndrome group of patients have significant difference between the control group in BMI, TG, HDL-C, LDL-C (P<0.05), there were statistically significant.(2) Hyperactivity of liver fire syndrome,dampness and phlegm syndrome and healthy population control group have differences in metabolic spectra.(3) There are certain differences in metabolism spectrum between hyperactivity of liver fire syndrome and dampness and phlegm syndrome. The two syndromes have significant difference in Phenylalanine, glutamic acid (P<0.05).(4) After treatment, patients have significant changes in metabolic spectrum. There are significant differences in the compounds such as:fructose, phenylalanine, 9、12-octadecadienoic acid (P<0.05)
Conclusions:(1) The use of metabonomics methods can successfully distinguish between hyperactivity of liver fire syndrome, dampness and phlegm syndrome and control group.(2) Preliminary view that phenylalanine, glutamic acid can be used as identification of hyperactivity of liver fire syndrome and dampness and phlegm syndrome to biological markers of metabonomics. (3) Preliminary view that fructose, phenylalanine,9、12-octadecadienoic acid has significant change after using antihypertensive drugs. (4) Considered overweight, obesity and dyslipidemia affect the incidence of hypertension dampness and phlegm syndrome.
方法：在江苏省中医院心内科门诊及体检中心前来就诊与体检人群中,选取原发性高血压患者,其中符合病例入选标准的肝火亢盛证型患者10例(a组),痰湿壅盛证患者10例(b组),健康对照组人群15例(K组)。观察入组人群的生命体征及相关生化指标,并抽取受试者空腹12小时静脉血,对其中a、b组20例患者中的10人进行了降压药物干预,4周后取得空腹12小时静脉血,作为治疗后组(y组)。经样品前处理后,用GC/TOF-MS(气相色谱飞行时间质谱)技术对两证型组患者、健康人群、治疗后组的血清进行全谱代谢组学分析。运用代谢组学方法及基本统计学方法对血样结果进行分析,根据各样本的主成分得分作图,判别其组间差异,得出相关生物标志物群。
结果：(1)痰湿壅盛组患者的BMI、TG、·HDL-C、LDL-C与健康人群对照组间出现了明显差异(P<0.05),存在统计学意义。(2)肝火亢盛组、痰湿壅盛组与健康人群对照组间,代谢谱存在明显差异。(3)肝火亢盛组与痰湿壅盛组之间的代谢谱亦存在一定差异,两组间有显著性差异的化合物为苯丙氨酸、谷氨酸(P<0.05)。(4)药物干预后,患者血清代谢谱出现明显的变化,有显著差异的化合物如：果糖、苯丙氨酸、亚油酸(P<0.05)。
结论：(1)运用代谢组学的研究方法可以成功区分高血压病肝火亢盛组、痰湿壅盛组和正常对照组。(2)初步认为苯丙氨酸、谷氨酸可作为鉴别肝火亢盛证组与痰湿壅盛证组的代谢组学生物标志物。(3)初步得出受降压药物影响较为显著的代谢物质如：果糖、苯丙氨酸、亚油酸。(4)认为超重、肥胖、血脂异常与高血压病痰湿壅盛证的发生存在相关性。
Objective: Observed the metabonomics features on hyperactivity of liver fire syndrome and dampness and phlegm syndrome of essential hypertension. Metabolites were compared between two syndrome for seeking the potential biomarkers. Meanwhile,observed the changes in metabolomics after treatment of hypertension and the effect of antihypertensive drugs on the metabolism of spectrum.
Methods:This study selects patients with essential hypertension as subject, among which 10 patients with hyperactivity of liver fire syndrome as Group a,10 cases of dampness and phlegm syndrome as Group B and 15 health comparison cases as Group K. The selection is made under the Case Selection Criteria. The participants are chosen from Department of Cardiology in Jiangsu Provincial Hospital of TCM and the physical examination center. The vital sign and biochemical parameters of each groups of participants are observed; 12 hours of fasting venous blood was collected; 10 of 20 patients among Group a & b are taken antihypertensive medical for 4 weeks before obtain 24 hours of fasting venous blood. Thus these 10 patients are arranged in a new group (Group y). After the proper treatment of samples, a wide spectrum of plasma metabonomics analysis is organized on the blood sample of patients with two syndromes, healthy people and people in treatment. Using basic statistical methods and metabolomics approach to analyze the results of the blood sample.According to the principal component score plot of samples, can distinguish differences between groups and related biological markers can be obtained.
Results:(1) Dampness and phlegm syndrome group of patients have significant difference between the control group in BMI, TG, HDL-C, LDL-C (P<0.05), there were statistically significant.(2) Hyperactivity of liver fire syndrome,dampness and phlegm syndrome and healthy population control group have differences in metabolic spectra.(3) There are certain differences in metabolism spectrum between hyperactivity of liver fire syndrome and dampness and phlegm syndrome. The two syndromes have significant difference in Phenylalanine, glutamic acid (P<0.05).(4) After treatment, patients have significant changes in metabolic spectrum. There are significant differences in the compounds such as:fructose, phenylalanine, 9、12-octadecadienoic acid (P<0.05)
Conclusions:(1) The use of metabonomics methods can successfully distinguish between hyperactivity of liver fire syndrome, dampness and phlegm syndrome and control group.(2) Preliminary view that phenylalanine, glutamic acid can be used as identification of hyperactivity of liver fire syndrome and dampness and phlegm syndrome to biological markers of metabonomics. (3) Preliminary view that fructose, phenylalanine,9、12-octadecadienoic acid has significant change after using antihypertensive drugs. (4) Considered overweight, obesity and dyslipidemia affect the incidence of hypertension dampness and phlegm syndrome.
引文
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