基于蛋白质组学和代谢组学对中医痰湿体质肥胖症病变机制的相关研究

发布时间：2018-02-27 06:10

本文关键词： 中医痰湿体质肥胖症蛋白质组学代谢组学病变机制　出处：《浙江中医药大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的通过对平和质正常者、超重者(痰湿体质和非痰湿体质)、及痰湿体质肥胖症患者这四组血清差异蛋白、及差异代谢物的分析、对比研究,揭示中医痰湿体质及肥胖症形成的病理基础,进一步阐明中医痰湿体质与肥胖症病变的相关机制,为中医痰湿体质治疗学提供理论和临床依据。方法本研究采用蛋白质指纹图谱技术及高效液相色谱-飞行时间质谱联用(HPLC-Q-TOF-MS)技术,以平和质正常者、超重者(痰湿体质和非痰湿体质)、及痰湿体质肥胖症患者的血清为样本,通过对比、分析上述四组的实验数据,探讨各组相关血清蛋白质组及代谢组的差异表达。结果1.与平和质正常组相比较:①非痰湿质超重组与平和质正常组相比:蛋白质组学研究显示两组未见显著的差异蛋白;在代谢组学研究中共鉴定出5种血清差异代谢物:Alpha-N-Phenylacetyl-L-glutamine、PGF2α diethyl amide、3-(Uracil-1-yl)-L-alanine、Propionyl-L-carnitine、及 LysoPC(18:3(6Z,9Z,12Z))。②痰湿质超重组与平和质正常组相比:蛋白质组学研究显示两组未见显著的差异蛋白;在代谢组学研究中共鉴定出8种血清差异代谢物:acetonide、N-gamma-L-Glutamyl-L-Phenylalanine、Decanoyl-L-carnitine、L-Arginine、O-octanoyl-R-Carni-tine、N-palmitoyl serine、Phytosphingosine、C17Sphinganine。③痰湿质肥胖组与平和质正常组相比:蛋白质组学研究中共鉴定出3种差异蛋白质:分别为DNA依赖性蛋白激酶催化亚单位(DNA-dependent protein kinase catalytic subunit)、FBW1A(F-box/WD repeat-containing protein 1A)、LARG(Glycosyltransferase-like protein LARGE1);在代谢组学研究中共鉴定出8种血清差异代谢物:LysoPC(18:3(6Z,9Z,12Z))及 LysoPC(18:3(9Z,12Z,15Z))、PC(O-18:1(9Z)/0:0)、Propionyl-L-camitine、Alpha-N-Phenylacetyl-L-Glutamine、LysoPE(0:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z))、PE(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0)、PGF2αdiethylamide。2.与痰湿质超重组相比较:①非痰湿质超重组与痰湿质超重组相比:蛋白质组学研究显示两组未见显著的差异蛋白;在代谢组学研究中共鉴定出10 种血清差异代谢物:Hydroxyprolyl-Tyrosine、3-(Uracil-1-yl)-L-alanine、acetonide、L-Cami-tine、N-Oleoyl-L-Serine、PE(20:4(5Z,8Z,11Z,14Z)/0:0)、N-palmitoyl serine、PS(O-18:0/0:0)、Decanoyl-L-carnitine、LysoPE(20:3(11Z,14Z,17Z)/0:0)。②痰湿质肥胖组与痰湿质超重组相比:蛋白质组学研究显示两组未见显著的差异蛋白;在代谢组学研究中共鉴定出9种血清差异代谢物:LysoPC(18:3(9Z,12Z,15Z))及 LysoPC(18:3(6Z,9Z,12Z))、Phytos-phingosine、LysoPE(20:3(11Z,14Z,17Z)/0:0)及 LysoPE(0:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z))、acetonide、Alpha-N-Phenylacetyl-L-Glutamine、N-Oleoyl-L-Serine、PC(0-18:1(9Z/0:0))。结论1.运用蛋白质组学对比分析,痰湿质肥胖组与平和质正常组相比存在血清差异蛋白表达,其余组组之间差异无统计学意义,提示中医痰湿体质肥胖症患者存在着蛋白质的差异表达。2.运用代谢组学对比分析,各组之间均存在血清差异代谢物;其中痰湿质肥胖组与痰湿质超重组、平和质正常组相比,存在代谢物Alpha-N-Phenylacetyl-L-Glutamine 及 LysoPC(18:3(6Z,9Z,12Z))差异表达,且 LysoPC(18:3(6Z,9Z,12Z))数值变化为:痰湿质肥胖组痰湿质超重组平和质正常组;提示中医痰湿体质肥胖症患者存在着能量、脂肪酸等代谢异常。3.本实验结果提示,运用代谢组学,有利于中医痰湿质及其肥胖症的早期检测。
[Abstract]:The purpose of gentleness of normal, overweight (phlegm dampness and non phlegm dampness constitution, phlegm dampness constitution) and obesity patients of the four groups of serum proteins and metabolites between research and analysis, comparison, reveal the pathological basis of phlegm dampness constitution and obesity formation, further elucidate the mechanism of phlegm wet physique and obesity disease, for the treatment of phlegm dampness constitution to provide theoretical and clinical basis. Based on the method of protein fingerprinting technology and high performance liquid chromatography time of flight mass spectrometry (HPLC-Q-TOF-MS) technology, with the gentleness of normal, overweight (phlegm dampness and non phlegm dampness constitution). And phlegm constitution in obese patients serum samples, by contrast, analysis of the experimental data of the four groups, to investigate the expression difference of related serum protein group and metabolic group. Results 1. with the gentleness of normal group compared with non phlegm: 1. Quality of overweight and normal quality compared to the normal group: proteomics studies show no significant difference between the two groups in the protein; metabonomics study identified 5 different serum metabolites: Alpha-N-Phenylacetyl-L-glutamine, PGF2 alpha diethyl amide, 3- (Uracil-1-yl) -L-alanine, Propionyl-L-carnitine, and LysoPC (18:3 (6Z, 9Z, 12Z)). The phlegm overweight and normal quality compared to the normal group: proteomics study showed no significant difference between the two groups in the protein; metabonomics study identified 8 different serum metabolites: acetonide, N-gamma-L-Glutamyl-L-Phenylalanine, Decanoyl-L-carnitine, L-Arginine, O-octanoyl-R-Carni-tine, N-palmitoyl, serine, Phytosphingosine, C17Sphinganine. and phlegm dampness obesity compared with the gentleness of normal group: proteomics study identified 3 different proteins: DNA dependent protein respectively. Kinase catalytic subunit (DNA-dependent protein kinase catalytic subunit), FBW1A (F-box/WD repeat-containing protein 1A), LARG (Glycosyltransferase-like protein LARGE1); in the metabonomic study identified 8 different serum metabolites: LysoPC (18: 3 (6Z, 9Z, 12Z) and LysoPC (18:3) (9Z, 12Z, 15Z) (O-18:1), PC (9Z) /0:0), Propionyl-L-camitine, Alpha-N-Phenylacetyl-L-Glutamine, LysoPE (0:0/22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z), PE (22:6) (4Z, 7Z, 10Z, 13Z, 16Z, 19Z) /0:0), PGF2 alpha diethylamide.2. and phlegm overweight group comparison: the non phlegm dampness phlegm overweight and overweight compared: proteomics studies show no significant difference between the two groups in the protein; metabonomics study identified 10 different serum metabolites: Hydroxyprolyl-Tyrosine, 3- (Uracil-1-yl) -L-alanine, acetonide, L-Cami-tine, N-Oleoyl-L-Serine, PE (20:4 (5Z, 8Z, 11Z, 14Z) /0:0), N-palmitoyl serine (O-18:0/0:0), PS, Decanoyl-L-carnitine, LysoPE (20:3 (11Z, 14Z, 17Z) /0:0). The phlegm dampness phlegm dampness obesity group and overweight compared: proteomics studies show no significant difference between the two groups in the protein metabolism; the study group identified 9 serum metabolite differences: LysoPC (18:3 (9Z, 12Z, 15Z) and LysoPC (18:3) (6Z, 9Z, 12Z), Phytos-phingosine (20:3), LysoPE (11Z, 14Z, 17Z) and LysoPE (/0:0) 0:0/22:6 (4Z, 7Z, 10Z, 13Z, 16Z 19Z, acetonide, Alpha-N-Phenylacetyl-L-Glutamine)), PC (0-18:1, N-Oleoyl-L-Serine, (9Z/0:0) 1.). Conclusion using proteome comparative analysis, phlegm and obesity group and normal quality compared to the normal group there was no significant difference of serum protein, the differences between the remaining groups, prompting phlegm dampness constitution in patients with obesity differential expression protein by.2. metabolism Comparative analysis of proteomics, there are differences between the groups in serum metabolites; phlegm dampness phlegm dampness obesity group and overweight, compared with normal quality normal group, Alpha-N-Phenylacetyl-L-Glutamine and LysoPC are metabolites (18:3 (6Z, 9Z, 12Z)) and LysoPC (differential expression, 18:3 (6Z, 9Z, 12Z)) numerical change: phlegm dampness phlegm dampness obesity group, overweight group and normal group flat matter; that of phlegm dampness constitution in obese patients are energy,.3. abnormal fatty acid metabolism of the experimental results suggest that the use of metabolomics, is conducive to the early detection of TCM phlegm and obesity.

【学位授予单位】：浙江中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R259

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