银屑灵治疗寻常型银屑病血清及尿液代谢组学的初步研究

发布时间：2018-01-02 10:36

本文关键词：银屑灵治疗寻常型银屑病血清及尿液代谢组学的初步研究　出处：《广州中医药大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的：本研究主要采用液质联用技术分析银屑灵片治疗前后寻常型银屑病患者血清及尿液代谢状态的变化,并与健康对照组进行比较,从而了解寻常型银屑病患者血清及尿液代谢轮廓的基本特征,并从代谢的层面阐述银屑灵片治疗寻常型银屑病的可能作用机制,为银屑灵治疗寻常型银屑病提供有效证据。方法：纳入2014年2月-2015年9月在广东省中医院皮肤科门诊就诊且与课题标准要求相符合的银屑病患者予银屑灵片治疗。在治疗前后(第0周和第12周)分别对各项临床评价指标进行评估,并用促凝管以及尿管分别采集患者晨起空腹的血液5ml及中段尿10ml。采用液质联用技术检测分析患者治疗前后血清及尿液代谢状态的变化,并寻找差异性、内源性代谢物,从而筛选出寻常型银屑病患者及银屑灵片治疗后发生改变的潜在生物标志物。结果：本研究共纳入寻常型银屑病患者18例,同时在广东省中医院体检中心纳入健康对照组共32例,其与治疗组在性别、年龄方面差异无统计学意义。主要采用具有高通量、高灵敏度和精确度的UPLC/Q-TOFMS技术对收集的血清及尿液标本进样检测分析,并通过主成分判别分析、偏最小二乘法-判别分析及正交潜变量投影-判别分析等方法进行模式识别,建立数学模型。寻常型银屑病患者血清及晨尿代谢组学治疗前后与健康对照组比较,代谢轮廓较为清晰,区分明显：治疗前与健康对照组的血清及尿液代谢生物标志物提示,寻常型银屑病与脂类、维生素、氨基酸以及辅酶等相关；血清治疗前后的代谢途径主要以脂类代谢为主,考虑与银屑病可能导致的脂类代谢紊乱相关,其中多为甘油三酯与磷脂的代谢；而晨尿治疗前后的代谢生物标志物与治疗前与健康组趋于相似。根据治疗前与健康对照组的血清及晨尿的生物标志物,银屑病与健康组存在代谢差异,其代谢紊乱与脂类、氨基酸、维生素等相关；银屑病患者血清与晨尿的代谢差异物中Ceramide (dl8:1/9Z-18:1)与Ceramide (dl8:1/20:0)均属磷脂代谢中神经酰胺类物质,经治疗后均存在明显下降,体现出银屑灵的调节作用,考虑可能为银屑病发生发展以及银屑灵调控作用的关键,但需大量的重复实验加以证明。结论：寻常型银屑病的血清及尿液的代谢与健康对照组之间存在明显差异,经银屑灵治疗后,其代谢差异发生明显改变且治疗后的代谢数据趋于健康正常组；从代谢组学上说,银屑灵治疗寻常型银屑病具有研究价值,结合相关代谢生物标志物,可为进一步发掘银屑灵对银屑病的作用机制与靶点提供有力的科学依据。
[Abstract]:Objective: to study the changes of serum and urine metabolism in patients with psoriasis vulgaris before and after treatment with Yinshiling tablets by liquid / mass spectrometry, and to compare the results with those of healthy controls. In order to understand the basic characteristics of the metabolic profile of serum and urine in patients with psoriasis vulgaris, and to explain the possible mechanism of Yinshiling tablet in the treatment of psoriasis vulgaris from the level of metabolism. To provide effective evidence for the treatment of psoriasis vulgaris. Methods:. Patients with psoriasis admitted to the Department of Dermatology of Guangdong Provincial Hospital of Chinese Medicine from February 2014 to September 2015 were treated with Yinshinling tablets before and after treatment (. Each clinical evaluation index was evaluated at week 0 and week 12 respectively. The patients' fasting blood 5ml and middle urine 10ml were collected from the morning, and the changes of serum and urine metabolism before and after treatment were detected by liquid-mass spectrometry. And search for the difference, endogenous metabolites, so as to screen out the potential biomarkers of psoriasis vulgaris patients and Yinshinling tablets after treatment. Results: 18 patients with psoriasis vulgaris were included in this study. At the same time, 32 cases of healthy control group were included in the physical examination center of Guangdong traditional Chinese medicine hospital. There was no significant difference in sex and age between the treatment group and the treatment group. A highly sensitive and accurate UPLC/Q-TOFMS technique was used to detect and analyze the serum and urine samples collected and analyzed by principal component discriminant analysis (PCA). Partial least squares discriminant analysis and orthogonal latent variable projection-discriminant analysis are used for pattern recognition. The metabolic profile of serum and morning urine of patients with psoriasis vulgaris was clearer than that of healthy controls before and after treatment. The results showed that the metabolic biomarkers of serum and urine before treatment and healthy control group suggested that psoriasis vulgaris was associated with lipid, vitamins, amino acids and coenzymes. The main metabolic pathway before and after treatment was lipid metabolism, which was related to the disorder of lipid metabolism caused by psoriasis, most of which were triglyceride and phospholipid metabolism. However, the metabolic biomarkers before and after morning urine treatment were similar to those in the healthy group before and after treatment. According to the biomarkers of serum and morning urine before treatment and healthy control group, there were metabolic differences between psoriasis group and healthy group. Its metabolic disorder is related to lipids, amino acids, vitamins and so on. (Ceramide dl8: 1 / 9Z-18: 1) and Ceramide dl8: 1 / 20: 0). They all belong to ceramides in phospholipid metabolism. After treatment, there is a significant decrease, which reflects the regulatory effect of silver shillings, which may be the key to the occurrence and development of psoriasis and the regulatory role of silver shillings. Conclusion: the metabolism of serum and urine in psoriasis vulgaris is significantly different from that in healthy control group. The metabolic differences were obviously changed and the metabolic data after treatment tended to normal group. From the metabonomics point of view, Yinshinling treatment of psoriasis vulgaris has the research value, combined with the related metabolic biomarkers, it can provide a powerful scientific basis for further exploring the mechanism and target of Yinshinling on psoriasis.
【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R275.9

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