| Objectives:This study was designed to find the basic evolution law of psoriasis vulgaris syndromes and the differences markers between blood heat and blood dryness syndrome in metabonomics research, to clarify the nature of different syndrome types of TCM syndromes, and to evaluate the overall efficacy of the series of treating blood decoctions by observing the effect of orally taking series of decoctions prescriped according to blood differentiation, including cooling blood and detoxification decoction, nourishing blood and detoxification soup and promoting blood and detoxification decoction, to study the TCM decoctions’ functional targets and its’mechanism through analysing the patients’serum before and after effective treatment using metabonomics methods.Methods:Clinical research:This research adopted a prospective, randomized, double blind, placebo-controlled method, and the ratio of the treatment group and the control group was 2:1. The patients were checked every week and made a syndrome differentiation every follow-up. The treatment group was treated with the medication decotions acorrding to syndrome adjusting, which were cooling blood and detoxification decoction for blood-heat syndrome, nourishing blood and detoxification soup for blood-dryness syndrome, and promoting blood and detoxification decoction for blood-stasis syndrome, while the control group was given placebo decoction with no change. Both of the two groups were topically treated with Vaseline ointment, and the treatment duration was 8 weeks. The syndrome changes were recorded and analysed, and PASI60 was defined as the main curative effect evaluation standard.Experiment study:The psoriasis patients peripheral blood serum of cases who participating in clinical research, according to the TCM syndrome type situation, treatment group effective treatment (PASI60) before and after treatment, psoriasis illness weight, body mass index, whether with metabolic diseases when grouping, were collected and analysed with metabonomics methods, using positive and negative modes UPLC-MS detecting metabolites. The test results were analysed by using PCA and PLS-DA, and supervised OPLS-DA model method was finally used, whose VIP value (VIP> 1) combined with t-test p values (p< 0.05) were used to find the difference expression of metabolites. Searching online databases (Metlin and KEGG) by comparing the mass spectrum of mass-to-charge ratio m/z or accurating molecular weight method were used for qualitative metabolites and ultimately determining the metabonomic pathways.Results:105 cases of patients with psoriasis vulgaris fom Beijing Chinese medicine hospital dermatology department affiliated to the Capital Medical University, were recruited from May 2015 to January 2016, and 81 of which were included, in wich 74 cases finally, treatment group 50 cases, control group 24 cases, were analysed with intentional analysis method (ITT) to collect data. The treatment group and control group patients were devided into groups of gender, whether to have a family history of psoriasis, whether with other disease history, in the begaining, and analysed with chi-square test content for the two groups of syndrome type distribution, variance analysis for the patients age, disease course and PASI score groups, and all contents of the two groups had no statistical difference (P> 0.05), so the baseline differences between the two groups were comparable.54 cases, including 36 cases treatment group and 18 the control group, and who were observed fully 8 weeks, were analysed to finding the evolution law. Of the blood heat syndrome, the proportion of the treatment group was 73.3%(11/15), the placebo group was 60.0% (6/10), two groups was no statistically significant difference (RR= 0.6667, P= 0.6667). Of the blood dryness syndrome, the treatment group was 35.3%(6/17), the placebo group was 0% (0/5). Of blood stasis syndrome, the treatment group was 100% (4/4), the control group was 100%(3/3). Due to the relatively less number in the blood dryness syndrome and blood stasis cases, there could not be statistical analysis.PASI60 of the treatment group was 44.0% (22/50), the control group was 12.5%(3/24), and the curative effect of treatment group was statistically significant better than the placebo group (P= 0.009< 0.05). PASI50 was 58% in treatment group and 54.2% in control group, PASI75 was 16.0% in treatment group,4.2% in control group, and the two sets of results were compared with chi-square test and rank and inspection, no statistical difference.50 cases of the treatment group, whose treatment effect was good (PASI60), and of which 10 cases was blood-heat syndrome,9 cases was blood-dryness syndrome,3 cases was blood stasis syndrome, and the treatment effect of deviation (< PASI60),13 cases was blood heat syndrome,12 cases was blood dryness syndrome in,3 cases was blood stasis syndrome, the distribution and the treatment effect was no significant difference (chi-square= 0.026, P= 0.026). In better effect treatment group,5 example in the course of 8 weeks treatment did not change, while 17 example changed, and of poor therapeutic effect,5 example unchanged,23 example changed, and it was no obvious difference in the two groups whether the syndrome type changed (Chi-square= 0.179, P= 0.179). No serious side effect occurred in the treatment group or the control group.It was found that the differences between blood heat syndrome group with 19 samples and blood dryness syndrome group with 12 samples was obvious using the metabonomics analysis, and 11 kinds of metabolites were finally found, with 5 in positive mode and 6 in negative mode, which were:3,4,5-Trimethoxycinnamic acid, Choline, tetracosahexaenoic acid, Thiamine acetic acid, Ubiquinone-1,4-hydroxybutanoic acid, Deoxycholic acid, L-beta-aspartyl-L-glutamic acid, Orotidine, TG(8:0/8:0/8:0) and β-L-Fucose-1-phosphate.It was found that differences before and after treatment with obvious change using the metabonomics analysis, in samples of 13 cases who achieving PASI60 in treatment group, and finally found 18 kinds of metabolites,11 is mode, negative mode 7, wich were:Cortisone, L-Urobilinogen, PA (15:1(9Z)/22:4(7Z,10Z,13Z,16Z)), PC (18:0/18:4(6Z,9Z,12Z,15Z)), PC(18:1(9Z)/4:0), PC (20:0/14:1(9Z)), PC (20:4(8Z, 11Z,14Z,17Z)/18:3(6Z,9Z,12Z)), PG (12:0/20:5(5Z,8Z, 11Z,14Z,17Z)), PG (P-18:0/20:4(5Z,8Z,11Z,14Z)), Phenyllactic acid, Traumatic Acid,16-hydroxy hexadecanoic acid,4-hydroxybutanoic acid, L-gamma-glutamyl-L-isoleucine, MG (0:0/16:1(9Z)/0:0), PA (20:4(5Z,8Z,11Z,14Z)/18:4(6Z,9Z,12Z,15Z)), PG (20:3(8Z, 11Z,14Z)/20:0), and PS (21:0/18:3(6Z,9Z,12Z)).Besides, this research had studied 12 patients whose PASI<10, defined as light group,and 24 patients whose PASI≥10, defined as heavy group, and it was found that the differences between two groups of metabolites including 39 species, which were 17 positive mode, and negative mode 22.10 cases of normal weight group(18.5<BMI<24.0), and 24 cases of overweight obesity group (BMI>24.0) before treatment,21 species differences metabolites were found,8 kinds positive mode, negative mode 13.13 cases with no combination of metabolic diseases and 21 cases combining metabolic disorders of patients with psoriasis had 45 kinds of differences metabolites, positive mode 10, and negative mode 35.Conclusion:It was found that the three basic syndromes of psoriasis vulgaris could be in any way change, and the most common change trend is by blood heat evolved into blood dryness syndrome according this research, and blood heat and blood stasis syndrome are unstable type, blood dryness syndrome is relatively stable. Since the blood differentiation series treatment effect is better than with no change in psoriasis vulgaris, when conducting TCM clinical research, the design should be based on the characteristics of TCM basic theory, and which could highlight the advantages of TCM treatment. The technique of metabonomics can be used in analyzing psoriasis in different syndrome types and treated with Chinese medicine before and after treatment, and the metabolites in different syndrome types is of different metabolic state may be one of the essences of syndrome types. In addition, promoting the biosynthesis, balancing the synthesis of steroid hormones in the body and thus exert anti-inflammatory mechanisms, or improving energy metabolism may be the mechanism of traditional Chinese medicine treatment.
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