| In Traditional Chinese Medicine (TCM), hyperlipidemia and atherosclerosis belong to the syndrome of phlegm-dampness and blood stasis, and the latter are the important pathogenesis of the former. The phlegm-stasis syndrome may be the manifestations resulted from some changed proteins that are closely related to hyperlipidemia and atherosclerosis. So, it will help to reveal the biochemistry basis and pathogenesis of phlegm-stasis syndrome clearly to study the relationship between the changed proteins and phlegm-stasis syndrome in hyperlipidemia and atherosclerosis.This research is an important part of the project "Study on the Proeomics about Phlegm and Blood Stasis Syndrome in Hyperlipidemia and Atherosclerosis", which is one of the projects "the key problems in TCM" sponsored by National Natural Science Foundation. Combining the TCM basical theory with modern scientific technology, the research explored the change of syndromes due to different protein's expression levels and the relationship between the changed proteins and TCM syndromes or a lot of related factors.METHODS1. Gathering plasm samples from 146 patients of hyperlipidemia and atherosclerosis, controlled with 37 normal plasm samples. In the patients, there are 32 Phlegm syndromes (PS), 38 Blood stasis syndromes (BSS), 41 Phlegm-Stasis syndromes (PSS), and 35 Non-Phlegm-or-Blood stasis syndromes (NPBSS) .All samples were studyed by the 2-DE eletrophoresis systems of GE company.2. Gel atlas of the plasm are analysed by Imagmaster 2-DE platinum 6.0 made by GE company.3. Typical components of different Phlegm and Blood stasis syndromes are aquired by Fisher discrimination. With these components we can discriminate different syndromes, then get relationship analysis by graphical model.RESULTS1. After the gels were analyzed by the software, the proteins with 70% varietywere selected. (1) There are thirty-one marked proteins in hyperlipemia and atherosclerosis.There are eighteen proteins up-regulation and thirteen proteins down-regulation in the patient group compared with the controlling group.(2) There are sixteen proteins with increasing tendency in express quantity, fifteen proteins with decreasing tendency.(3) In the probabal marked proteins of different Phlegm and Blood stasis syndromes, the minimum proteins in expression quantity are distributed in different syndromes, with 5 proteins in NPBSS, 3 in the phlegm syndrome, 8 proteins in BSS, 8 in PSS. The 8 proteins in PSS include 2 proteins in BSS patients and 1 protein in PS. The maximum proteins in expression quantity are distributed in different syndromes, with 9 in NPBSS, 8 proteins in PS, 6 proteins in BSS, 7 proteins in PSS. The 7 proteins in PSS include 3 proteins in BSS and 1 protein in PS.(4) Some changing rules among syndromes are observedo , Proteins Increased Proteins DecreasedsyndromesPS-PSS-BSS 1539,1485,1688;\?' 1481' 1521' 1666'1383> 1314> 1492= 1563, 1290, 1412, 1484,1502,1642,1643;1486,1505,15131383> 1456>1539' 1436> 1521> 1635, 1666,1688,1314,1514;1412,1549,16621383,1481,1314;1485,1563,1635,1412,1383'1539'1688;I436' 1521' 1666> 1412'1314,1373;1482;1470,1504,1515NPBSS-PS-BSS-PSS 1383,1314;1412 NPBSS-PS-PSS-BSS 1539,1688;<sub><sub><sub><sub><sub><sub><sub><sub><sub><sub>1666,1436<sub><sub><sub><sub><sub><sub><sub><sub><sub><sub>2. There lies significant difference in typical components, which are used to dicriminate the two groups. The components are discovered by Fisher dicrimination on eleven variance proteins with 100% variety. The proteins contributing a lot to the typical parts from them are selected as the marked ones.(1) The proteins which are used to discriminate hyperlipidemia and atherosclerosis from the healthy control are 1481 and 1521 respectively;(2) The proteins which are used to discriminate NPBSS from PBS are 1383 and 1635;(3) The proteins which are used to discriminate PS from BSS are 1521,1563, 1688 and 1635;(4) The proteins which are used to discriminate PS from PBSS arel481,1539 and 1635;(5) The proteins that are used to discriminate BSS from PBSS arel 481,1539 and 1635. 3. The relationship of the marked proteins and the factors(1) The relationship between two proteins (1521 and 1481) used to discriminate hyperlipidemia and atherosclerosis from the healthy control and all kinds of factors shows, 1521 is related to TQ HDL, the thick of inner membrane, and some chronic diseases (including atherosclerosis and hypertension disease (HD)). 1481 is related to LDL, CRP, and atherosclerosis.(2) The relationship between the proteins (1383 and 1635) used to discriminate NPBSS from PBS, and all kinds of factors shows, 1383 is related to TC, HDL, LDL, AI, the thick of inner membrane and the area of the platelet, prerious atherosclerosis, family history and medication, exercising. 163 5 is related to CRP, deficiency of kidney Qi and spleen Qi, prerious atherosclerosis.(3) The relationship between the proteins (1521, 1563, 1688 and 1635) which used to discriminate PS from BSS, and all kinds of factors, 1521 is related to deficiency of kidney Qi, TC, TQ AI, blood viscosity in shear rate 30, medical, tobacco and alcohol. 1563 is related to deficiency of kidney Qi, radius of cavity, area of the platelet, blood viscosity in shear rate 30, prerious diseases (including atherosclerosis and HD), medication, smoking and drinking;1666 is related to deficiency of kidney Qi and heart Qi, the thick of inner membrane, medication, smoking and drinking. 1688 is related to prerious diseases (including atherosclerosis and HD), medication, smoking and drinking.(4) The relationship between the proteins (1481,1539 andl635) which used to discriminate PS from PBSS, and all kinds of factors show, 1481 is related to deficiency of kidney Qi and heart Qi and spleen Qi, AI, CRP, blood viscosity in shear rate 5, PLT, family histort, smoking and drinking;1539 is related to deficiency of kidney Qi and heart Qi and spleen Qi, TC, CRP, radius of cavity, Fg, blood viscosity in shear rate 1, 5 and 200, body weight index, prerious diseases (including atherosclerosis and HD), family histort, medication, smoking and drinking;163 5 is related to deficiency of kidney Qi and heart Qi and spleen Qi, blood viscosity in shear rate 1 and 200, PLT, Family history.(5) The relationship between the proteins (1481, 1539andl635) which used to discriminate BSS from PBSS, and all kinds of factors show, 1456 is related to deficiency of kidney Qi and heart Qi and spleen Qi, thick of inner membrane, blood viscosity in shear rate 1, Fg andHCT, Family history, exercising, smoking anddrinking;1563 is related to blood viscosity in shear rate 5 and 30, HGB and HCT, prerious As, medication, smoking and drinking.COCLUSION1. Firstly apply plasma proteornic technology to the study on phlegm and blood stasis syndrome in hyperlipemia and atherosclerosis.2. Firstly adopt Fisher discriminatory which filt the typical components of the phlegm and blood stasis syndrome and the Graphical model which analyse the realationship between typical components and various related factors3. Variety of proteins in express quantity exists in different PBS syndromes or between patients and the healthy control. We also found the regular changes of some proteins are in different PBS syndromes.4. The three syndromes, PS, BSS and PSS, respectively have marked proteins, hi this study, the marked proteins of PSS contain some marked proteins of PS and BSS. The proportion of BSS is over PS, which shows PBSS is a syndrome of blood stasis syndrome combined with the phlegm syndrome.5. From the relationship and the change discipline among the PBS, we can draw the conclusion that most differential expression proteins present regular increasing or decreasing in express quantity, such as atherosclerosis NPN-*BS — PS^BSS^PBSS or PS — BSS — PBSS, NPBSS — PS — BSS, which approve that the change rule of the PBS is mostly from PS to BSS.Some findings about the Fisher model analysis and graphical model on the gels aquired by the imagemaster 2 DE platinum 6.0.1. 1521 and 1481 are the marked proteins in the plasma of Hyperlipidemia andatherosclerosis patients.2. 1383 and 1635 are the marked proteins in the plasma of Hyperlipidemia and atherosclerosis PBS patients.3. 1481,1539 and 1635 are marked proteins in the plasma of PS patients.4. 1521, 1563, 1666 and 1688 and the marked proteins in the plasma of BSS patients.5. 1456 and 1563 are the marked proteins in the plasma of PSS patients.6. The proteins using to dicriminate the diseases from the healthy controls are closely related to the function of the visceras in different syndromes. The PS relating marked proteins is correspondent to deficiency of kidney Qi, heart Qi and spleen Qi. The PBS relating marked proteinsis correspondent to deficiencyof kidney Qi and heart Qi. The PBSS relating marked proteins is correspondent to deficiency of kidney Qi and heart Qi, as well as spleen Qi. 7. The further analysis on the relationship between the marked proteins, related to different visceras, and the factors, such as the blood lipid, CRP, the index of blood rheology, the damaged degree of the vessel wall, medication, the history of other diseases, smoking and drinking, and also exercising.7.1 The relativity of the marked proteins of PBSThe marked protein 1383 which is correspondent to deficiency of kidney Qi, is related to TC, HDL, LDL, AI, the thickness of the inner membrane and the area of the plaque, the history of atherosclerosis, the family history, medication and exercising.The marked proteinsl635 which is correspondent to deficiency of kidney Qi and heart Qi, is related to CRP, the history of atherosclerosis.7.2 The relativity of the marked proteins of BSSThe marked proteins 1521 which is correspondent to deficiency of kidney Qi,is related to TC, TG, AI, blood viscosity in shear rate 30, medication, smokingand drinking.The marked proteins 1563 which is correspondent to deficiency of kidney Qiand heart Qi, is related to the thickness of the inner membrane and the area ofthe plaque, blood viscosity in shear rate 30, the history of atherosclerosis,medication, smoking and drinking.The marked proteins 1666 which is correspondent to deficiency of kidney Qiand heart Qi, is related to the thickness of the inner membrane, medication,smoking and drinking.The marked proteins 1688 which is correspondent to the history ofatherosclerosis and HD, medication, smoking and drinking.7.3 The relativity of the marked proteins of PSThe marked proteins 1481 which is correspondent to deficiency of kidney Qi, heart Qi and spleen Qi, is related to AI, CRP, blood viscosity in shear rate 5, PLT, the family history, smoking and drinking.The marked proteins 1539 which is correspondent to deficiency of kidney Qi, heart Qi and spleen Qi, is related to TC, CRP, the inner diameter of lumens, fibrinogen, blood viscosity in shear ratel/5/200, weight index, the history of atherosclerosis and HD, the family history, medication, smoking and drinking. The marked proteins 1635 which is correspondent to deficiency of kidney Qi, heart Qi and spleen Qi, is related to blood viscosity in shear ratel/200, PLT,the history of atherosclerosis and high blood press. 7.4 The relativity of the marked proteins of PBSSThe marked proteins 1456 which is correspondent to deficiency of kidney Qi, heart Qi and spleen Qi, is related to the thickness of the inner membrane, blood viscosity in shear ratel, fibrinogen and HCT, the family history, exercising, smoking and drinking.The marked proteins 1563 which is correspondent to deficiency of kidney Qi, heart Qi and spleen Qi, is related to blood viscosity in shear ratel /30, HGB and HCT, the history of atherosclerosis, medication, smoking and drinking.The above results provided not only the important evidence for the hypothesis "the significant difference of functional protein expression are existed between different syndromes, some kind of marked proteins are compatible, and some key proteins change in structure or function from the phlegm to the blood stasis", but also the molecular basis for the differentiation and changed rules of different syndromes in hyperlipidemia and atherosclerosis. These results have great scientific meaning and possible practical value to clarify the scientific essence of TCM syndromes.This article made comprehensive analysis on many influence factors. And results provide the important evidences for the outset, development and diagnosing standard of the syndromes in hyperlipidemia and atherosclerosis, and also give the guidance for individual treatment according to different syndromes. |
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