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
- Published：20 February 2023，
  
  Published Online：19 July 2022，
  
  Received：01 April 2022，
- 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

靶向脂质组学寻常型银屑病开玄补肾法生物标志物亚油酸代谢甘油磷脂代谢

Keywords

targeted lipidomicspsoriasis vulgarisKaixuan Bushen methodbiomarkerslinoleic acid metabolismglycerophospholipid metabolism

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