本文關(guān)鍵詞： 中醫(yī)痰濕體質(zhì) 肥胖癥 蛋白質(zhì)組學(xué) 代謝組學(xué) 病變機(jī)制　出處：《浙江中醫(yī)藥大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的通過對(duì)平和質(zhì)正常者、超重者(痰濕體質(zhì)和非痰濕體質(zhì))、及痰濕體質(zhì)肥胖癥患者這四組血清差異蛋白、及差異代謝物的分析、對(duì)比研究,揭示中醫(yī)痰濕體質(zhì)及肥胖癥形成的病理基礎(chǔ),進(jìn)一步闡明中醫(yī)痰濕體質(zhì)與肥胖癥病變的相關(guān)機(jī)制,為中醫(yī)痰濕體質(zhì)治療學(xué)提供理論和臨床依據(jù)。方法本研究采用蛋白質(zhì)指紋圖譜技術(shù)及高效液相色譜-飛行時(shí)間質(zhì)譜聯(lián)用(HPLC-Q-TOF-MS)技術(shù),以平和質(zhì)正常者、超重者(痰濕體質(zhì)和非痰濕體質(zhì))、及痰濕體質(zhì)肥胖癥患者的血清為樣本,通過對(duì)比、分析上述四組的實(shí)驗(yàn)數(shù)據(jù),探討各組相關(guān)血清蛋白質(zhì)組及代謝組的差異表達(dá)。結(jié)果1.與平和質(zhì)正常組相比較:①非痰濕質(zhì)超重組與平和質(zhì)正常組相比:蛋白質(zhì)組學(xué)研究顯示兩組未見顯著的差異蛋白;在代謝組學(xué)研究中共鑒定出5種血清差異代謝物: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痰濕質(zhì)超重組與平和質(zhì)正常組相比:蛋白質(zhì)組學(xué)研究顯示兩組未見顯著的差異蛋白;在代謝組學(xué)研究中共鑒定出8種血清差異代謝物:acetonide、N-gamma-L-Glutamyl-L-Phenylalanine、Decanoyl-L-carnitine、L-Arginine、O-octanoyl-R-Carni-tine、N-palmitoyl serine、Phytosphingosine、C17Sphinganine。③痰濕質(zhì)肥胖組與平和質(zhì)正常組相比:蛋白質(zhì)組學(xué)研究中共鑒定出3種差異蛋白質(zhì):分別為DNA依賴性蛋白激酶催化亞單位(DNA-dependent protein kinase catalytic subunit)、FBW1A(F-box/WD repeat-containing protein 1A)、LARG(Glycosyltransferase-like protein LARGE1);在代謝組學(xué)研究中共鑒定出8種血清差異代謝物: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.與痰濕質(zhì)超重組相比較:①非痰濕質(zhì)超重組與痰濕質(zhì)超重組相比:蛋白質(zhì)組學(xué)研究顯示兩組未見顯著的差異蛋白;在代謝組學(xué)研究中共鑒定出10 種血清差異代謝物: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痰濕質(zhì)肥胖組與痰濕質(zhì)超重組相比:蛋白質(zhì)組學(xué)研究顯示兩組未見顯著的差異蛋白;在代謝組學(xué)研究中共鑒定出9種血清差異代謝物: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))。結(jié)論1.運(yùn)用蛋白質(zhì)組學(xué)對(duì)比分析,痰濕質(zhì)肥胖組與平和質(zhì)正常組相比存在血清差異蛋白表達(dá),其余組組之間差異無統(tǒng)計(jì)學(xué)意義,提示中醫(yī)痰濕體質(zhì)肥胖癥患者存在著蛋白質(zhì)的差異表達(dá)。2.運(yùn)用代謝組學(xué)對(duì)比分析,各組之間均存在血清差異代謝物;其中痰濕質(zhì)肥胖組與痰濕質(zhì)超重組、平和質(zhì)正常組相比,存在代謝物Alpha-N-Phenylacetyl-L-Glutamine 及 LysoPC(18:3(6Z,9Z,12Z))差異表達(dá),且 LysoPC(18:3(6Z,9Z,12Z))數(shù)值變化為:痰濕質(zhì)肥胖組痰濕質(zhì)超重組平和質(zhì)正常組;提示中醫(yī)痰濕體質(zhì)肥胖癥患者存在著能量、脂肪酸等代謝異常。3.本實(shí)驗(yàn)結(jié)果提示,運(yùn)用代謝組學(xué),有利于中醫(yī)痰濕質(zhì)及其肥胖癥的早期檢測(cè)。
[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.

【學(xué)位授予單位】：浙江中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R259

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