Targeted Lipidomics Reveals Lipid Modulation of Kaixuan Bushen Method on Psoriasis Vulgaris

DAI Dan; CHEN Yanhua; HE Chunyan; WANG Shuo; SONG Ping

doi:10.13422/j.cnki.syfjx.20220749

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Targeted Lipidomics Reveals Lipid Modulation of Kaixuan Bushen Method on Psoriasis Vulgaris

更新时间：2023-01-17

- Targeted Lipidomics Reveals Lipid Modulation of Kaixuan Bushen Method on Psoriasis Vulgaris
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 4, Pages: 117-125(2023)
- 作者机构：
  
  1.中国中医科学院广安门医院，北京 100053
  2.中央民族大学，北京 100081
  3.湖北省中医院，武汉 430061
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20220749
  CLC： R22;R24;R969.1;O657
- Received：01 April 2022，
  
  Published Online：19 July 2022，
  
  Published：20 February 2023
- 稿件说明：
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代丹,陈艳华,何春燕等.基于靶向脂质组学探究开玄补肾法对寻常型银屑病的干预机制[J].中国实验方剂学杂志,2023,29(04):117-125.

DAI Dan,CHEN Yanhua,HE Chunyan,et al.Targeted Lipidomics Reveals Lipid Modulation of Kaixuan Bushen Method on Psoriasis Vulgaris[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(04):117-125.
代丹,陈艳华,何春燕等.基于靶向脂质组学探究开玄补肾法对寻常型银屑病的干预机制[J].中国实验方剂学杂志,2023,29(04):117-125. DOI： 10.13422/j.cnki.syfjx.20220749.

DAI Dan,CHEN Yanhua,HE Chunyan,et al.Targeted Lipidomics Reveals Lipid Modulation of Kaixuan Bushen Method on Psoriasis Vulgaris[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(04):117-125. DOI： 10.13422/j.cnki.syfjx.20220749.

摘要

目的

通过靶向脂质组学技术，从脂代谢角度探究开玄补肾法对寻常型银屑病的干预机制，为寻常型银屑病的诊断和治疗提供参考。

方法

选取2019年9月至2020年11月中国中医科学院广安门医院皮肤科门诊收治的26例寻常型银屑病患者作为研究对象（观察组），同期在该院预防保健科招募健康志愿者26例作为对照组，入组时予对照组及观察组采取静脉血以进行血脂指标和靶向脂质组学检测。观察组予开玄补肾法治疗，连续治疗12周后，比较治疗前后患者银屑病皮损面积和严重程度指数（PASI）以评估疗效，同时再次静脉抽血检测以比较治疗前后患者血脂水平和脂质代谢情况。靶向脂质组学分析采用超高效液相色谱串联质谱法（UPLC-MS/MS），色谱条件为ACQUITY UPLC BEH C

色谱柱（2.1 mm×100 mm，1.7 μm），流动相为乙腈-水（6∶4，含5 mmol∙L

-1

甲酸铵，A）和乙腈-异丙醇（1∶9，含5 mmol∙L

-1

甲酸铵，B）梯度洗脱，流速0.26 mL∙min

-1

；质谱条件为电喷雾离子源（ESI），正、负离子模式，扫描范围

50~1 200。建立主成分分析（PCA）和偏最小二乘法-判别分析（PLS-DA）模型筛选差异代谢物，鉴定差异代谢物并进行相关通路分析。

结果

经开玄补肾法治疗12周后，26例寻常型银屑病患者中PASI评分的下降率达50%以上的有22人，总有效率84.62%。寻常型银屑病患者血清中甘油三酯含量明显高于健康人（

0.05），经治疗后，甘油三酯水平明显降低（

0.05）。靶向脂质组学分析共筛选出寻常型银屑病潜在生物标志物43个，其中42个上调、1个下调，涉及亚油酸代谢、不饱和脂肪酸的生物合成、甘油磷脂代谢等7条信号通路；开玄补肾法对寻常型银屑病疗效的潜在生物标志物14个，其中6个上调、8个下调，涉及鞘脂代谢、亚油酸代谢和甘油磷脂代谢等5条信号通路；在健康人和寻常型银屑病患者、寻常型银屑病患者治疗前后的对比中，得到共同差异代谢物磷脂酰胆碱（PC）38∶0和神经酰胺（Cer）42∶1、共同的信号通路是亚油酸和甘油磷脂代谢通路。

结论

寻常型银屑病脂质代谢紊乱主要涉及鞘脂、甘油磷脂和亚油酸代谢通路，开玄补肾法可以对其中的亚油酸和甘油磷脂代谢通路进行调节，从而改善银屑病皮损。

Abstract

Objective

Through the targeted lipidomics， we explored the intervention mechanism of Kaixuan Bushen method on psoriasis vulgaris （PV） from the perspective of lipid metabolism， providing reference for the diagnosis and treatment of PV.

Method

Twenty-six patients with PV admitting the outpatient clinic of the Department of Dermatology， Guang'anmen Hospital， China Academy of Chinese Medical Sciences from September 2019 to November 2020 were selected as the research object （observation group）， and 26 sex- and age-matched healthy volunteers in the same period were recruited as control group. Venous blood was collected for lipid index and targeted lipidomics detection in the control and observation groups at inclusion. After 12 weeks of continuous treatment of Kaixuan Bushen method， the psoriasis area and severity index （PASI） was measured and compared before and after treatment to assess the clinical efficacy， while venous blood was collected again in the observation group to compare the blood lipid level and lipid metabolism of patients before and after treatment. Targeted lipidomics analysis was performed by ultra performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS） on an ACQUITY UPLC BEH C

column （2.1 mm×100 mm， 1.7 μm） with mobile phase of 5 mmol∙L

-1

ammonium formate in acetonitrile-water （6∶4， A）-5 mmol∙L

-1

ammonium formate in acetonitrile-isopropanol （1∶9， B） for gradient elution and flow rate of 0.26 mL∙min

-1

. Conditions of MS were electrospray ionization （ESI）， positive and negative ion modes， and scanning range of

50-1 200. Then principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA） models were developed to screen differential metabolites， and the differential metabolites were identified and the pathways were enriched.

Result

After 12 weeks of treatment with Kaixuan Bushen method， PASI score decreased by more than 50% in a total of 22 out of 26 patients with PV， suggesting the total effective rate was 84.62%. The serum triglyceride level of patients with PV was significantly higher than that of healthy individuals （

0.05）， and the triglyceride level was significantly reduced after treatment （

0.05）. Targeted lipidomics analysis screened a total of 43 potential biomarkers for PV， of which 42 were up-regulated and 1 was down-regulated， involving 7 signaling pathways such as linoleic acid metabolism， glycerophospholipid metabolism and unsaturated fatty acid biosynthesis. Moreover， there were 14 response makers for clinical efficacy of Kaixuan Bushen method on PV， of which 6 were up-regulated and 8 were down-regulated， involving five signaling pathways such as linoleic acid metabolism， glycerophospholipid metabolism and sphingolipids metabolism. In a comparison between healthy individuals and patients with PV and PV before and after treatment， the common differential metabolites were screened as phosphatidylcholine （PC） 38∶0 and ceramide （Cer） 42∶1， and the common pathways were linoleic acid and glycerophospholipid metabolic pathways.

Conclusion

The disorder of lipid metabolism in PV are largely due to abnormal sphingolipid， glycerophospholipid and linoleic acid metabolic pathways， of which Kaixuan Bushen method can regulate the glycerophospholipid and linoleic acid metabolism， thereby improving psoriatic lesions.

关键词

Keywords

references

BOEHNCKE W H ， SCHÖN M P . Psoriasis ［J］. Lancet ， 2015 ， 386 （ 9997 ）： 983 - 994 .

GREB J E ， GOLDMINZ A M ， ELDER J T ， et al . Psoriasis ［J］. Nat Rev Dis Primers ， 2016 ， 2 ： 16082 .

TAKESHITA J ， GREWAL S ， LANGAN S M ， et al . Psoriasis and comorbid diseases：Epidemiology ［J］. J Am Acad Dermatol ， 2017 ， 76 （ 3 ）： 377 - 390 .

WANG H L ， WANG Z Z ， RANI P L ， et al . Identification of PTPN22，ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes ［J］. Exp Dermatol ， 2017 ， 26 （ 11 ）： 1112 - 1117 .

曹爽，周妍妍，闫景东 . 中医药调控银屑病相关信号通路研究进展［J］. 中国实验方剂学杂志， 2021 ， 27 （ 15 ）： 243 - 250 .

中华中医药学会皮肤科分会 . 皮肤科分会银屑病中医治疗专家共识（2017年版）［J］. 中国中西医结合皮肤性病学杂志， 2018 ， 17 （ 3 ）： 273 - 277 .

高云逸，张晓彤，李宗友，等 . 基于玄府理论治疗寻常型银屑病［J］. 中国中医药信息杂志， 2020 ， 27 （ 3 ）： 113 - 116 .

宋坪，王晓旭，杨茂誉，等 . 开通玄府、通络解毒法治疗斑块状银屑病120例疗效观察［J］. 中医杂志， 2013 ， 54 （ 17 ）： 1476 - 1479 .

尹秀平，程晓菲，宋坪，等 . 消银颗粒和开玄补肾方对咪喹莫特诱导的银屑病样小鼠模型的影响［J］. 光明中医， 2019 ， 34 （ 2 ）： 220 - 224 .

王烁 . 寻常型银屑病代谢相关特征的临床及血清代谢组学初探［D］. 北京：北京中医药大学， 2019 .

钟森杰，熊霞军，张倩，等 . 主动脉弓缩窄术建立心力衰竭大鼠模型的病理过程观察与非靶向代谢组学分析［J］. 中国实验方剂学杂志， 2022 ， 28 （ 9 ）： 117 - 124 .

吴琳静，余雪纯，柯佳群，等 . 基于代谢组学的中药治疗化学性肝损伤研究进展［J］. 中国实验方剂学杂志， 2021 ， 27 （ 12 ）： 202 - 215 .

DONNELLY D ， AUNG P P ， JOUR G . The "-OMICS" facet of melanoma：Heterogeneity of genomic，proteomic and metabolomic biomarkers ［J］. Semin Cancer Biol ， 2019 ， 59 ： 165 - 174 .

JOHNSON C H ， IVANISEVIC J ， SIUZDAK G . Metabolomics：Beyond biomarkers and towards mechanisms ［J］. Nat Rev Mol Cell Biol ， 2016 ， 17 （ 7 ）： 451 - 459 .

ZENG C W ， WEN B ， HOU G X ， et al . Lipidomics profiling reveals the role of glycerophospholipid metabolism in psoriasis ［J］. Gigascience ， 2017 ， 6 （ 10 ）： 1 - 11 .

何春燕 . 基于UPLC-MS的寻常型银屑病血清脂代谢研究［D］. 北京：北京中医药大学， 2021 .

CAO H ， SU S M ， YANG Q ， et al . Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients ［J］. Lipids Health Dis ， 2021 ， 20 （ 1 ）： 16 .

LIU F ， WANG S P ， LIU B ， et al . （ R ）-Salbutamol improves imiquimod-induced psoriasis-like skin dermatitis by regulating the th17/tregs balance and glycerophospholipid metabolism ［J］. Cells ， 2020 ， 9 （ 2 ）： 511 .

赵辨 . 中国临床皮肤病学［M］. 南京：江苏科学技术出版社， 2017 ： 1008 - 1009 .

郑筱萸 . 中药新药临床研究指导原则（试行）［M］. 北京：中国医药科技出版社， 2002 ： 299 .

曲圣元 . 基于数据挖掘方法探究宋坪主任医师治疗银屑病用药经验［D］. 北京：北京中医药大学， 2020 .

MENTER A . Psoriasis and psoriatic arthritis overview ［J］. Am J Manag Care ， 2016 ， 22 （ Suppl 8 ）： 216 - 224 .

SOROKIN A V ， DOMENICHIELLO A F ， DEY A K ， et al . Bioactive lipid mediator profiles in human psoriasis skin and blood ［J］. J Invest Dermatol ， 2018 ， 138 （ 7 ）： 1518 - 1528 .

GAO Y L ， YI X M ， DING Y F . Combined transcriptomic analysis revealed AKR1B10 played an important role in psoriasis through the dysregulated lipid pathway and overproliferation of keratinocyte ［J］. Biomed Res Int ， 2017 ， 2017 ： 8717369 .

LI Y ， ZONG J X ， YE W J ， et al . Pithecellobium clypearia ：Amelioration effect on imiquimod-induced psoriasis in mice based on a tissue metabonomic analysis ［J］. Front Pharmacol ， 2021 ， 12 ： 748772 .

CHOQUE B ， CATHELINE D ， RIOUX V ， et al . Linoleic acid：Between doubts and certainties ［J］. Biochimie ， 2014 ， 96 ： 14 - 21 .

WANG Q Q ， MCCORMICK T S ， WARD N L ， et al . Combining mechanism-based prediction with patient-based profiling for psoriasis metabolomics biomarker discovery ［J］. AMIA Annu Symp Proc ， 2017 ， 2017 ： 1734 - 1743 .

ROSSAINT J ， NADLER J L ， LEY K ， et al . Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury ［J］. Crit Care ， 2012 ， 16 （ 5 ）： R166 .

MABALIRAJAN U ， REHMAN R ， AHMAD T ， et al . 12/15-Lipoxygenase expressed in non-epithelial cells causes airway epithelial injury in asthma ［J］. Sci Rep ， 2013 ， 3 ： 1540 .

WEAVER J R ， HOLMAN T R ， IMAI Y ， et al . Integration of pro-inflammatory cytokines，12-lipoxygenase and NOX-1 in pancreatic islet beta cell dysfunction ［J］. Mol Cell Endocrinol ， 2012 ， 358 （ 1 ）： 88 - 95 .

LI Y ， LIN P ， WANG S Y ， et al . Quantitative analysis of differentially expressed proteins in psoriasis vulgaris using tandem mass tags and parallel reaction monitoring ［J］. Clin Proteomics ， 2020 ， 17 ： 30 .

ZHAO J X ， WANG Y ， CHEN W W ， et al . Systems pharmacology approach and experiment evaluation reveal multidimensional treatment strategy of LiangXueJieDu formula for psoriasis ［J］. Front Pharmacol ， 2021 ， 12 ： 626267 .

朱黎霞，韦园诗，黄星星，等 . 基于UPLC-Q/TOF-MS分析痰瘀互结型冠心病患者的血浆脂质组学［J］. 中国实验方剂学杂志， 2020 ， 26 （ 1 ）： 110 - 117 .

MARTÍNEZ-UŇA M ， VARELA-REY M ， CANO A ， et al . Excess S -adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis ［J］. Hepatology ， 2013 ， 58 （ 4 ）： 1296 - 1305 .

ALVES-BEZERRA M ， COHEN D E . Triglyceride metabolism in the liver ［J］. Compr Physiol ， 2017 ， 8 （ 1 ）： 1 - 8 .

BUDOFF M . Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease ［J］. Am J Cardiol ， 2016 ， 118 （ 1 ）： 138 - 145 .

SHODA J ， UEDA T ， IKEGAMI T ， et al . Increased biliary group Ⅱ phospholipase A 2 and altered gallbladder bile in patients with multiple cholesterol stones ［J］. Gastroenterology ， 1997 ， 112 （ 6 ）： 2036 - 2047 .

LIU P P ， ZHU W ， CHEN C ， et al . The mechanisms of lysophosphatidylcholine in the development of diseases ［J］. Life Sci ， 2020 ， 247 ： 117443 .

HASEGAWA H ， LEI J ， MATSUMOTO T ， et al . Lysophosphatidylcholine enhances the suppressive function of human naturally occurring regulatory T cells through TGF- β production ［J］. Biochem Biophys Res Commun ， 2011 ， 415 （ 3 ）： 526 - 531 .

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