首页|培土清心颗粒治疗特应性皮炎的蛋白质组学研究

培土清心颗粒治疗特应性皮炎的蛋白质组学研究

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目的 采用血清蛋白质组学方法探讨培土清心颗粒(白术、连翘、白茅根、太子参等)治疗特应性皮炎的作用靶点。方法 选择特应性皮炎患者 5 例,以培土清心颗粒治疗 12 周,并以健康志愿者 5 例作为对照。对特应性皮炎患者治疗后的临床核心评价指标包括病情严重程度评分(EASI、SCORAD)、瘙痒程度评分、患者自评(POEM)、生活质量指数等进行评估。采用数据非依赖采集质谱(DIA-MS)技术检测血清样本,并根据P<0。05、变化倍数(Fold Change)>1。2 筛选出特应性皮炎患者与健康人群的血清差异蛋白,以及培土清心颗粒治疗前后特应性皮炎患者的血清差异蛋白。对差异蛋白进行GO功能富集分析和KEGG通路富集分析。结果 (1)与治疗前比较,特应性皮炎患者治疗后的临床核心评价指标包括病情严重程度评分(EASI、SCORAD)、瘙痒程度评分、患者自评(POEM)、生活质量指数等均得到明显改善,差异均有统计学意义(P<0。05,P<0。01)。(2)健康对照组及特应性皮炎组共分析出 28 个差异性蛋白,其中 12 个蛋白表达水平上升,16 个蛋白表达水平下降,包括ALAD(δ-氨基乙酰丙酸脱水酶)、LTA4H(白三烯A-4 水解酶)、CA1(碳酸酐酶 1)、F11(凝血因子XI)、LCP1(淋巴细胞胞浆蛋白 1)等。主要涉及PI3K-AKT信号通路、脂质与动脉粥样硬化、ECM-受体相互作用、血小板活化、NF-κB信号通路、中性粒细胞外陷阱形成等信号通路。(3)特应性皮炎患者经培土清心颗粒治疗前后共分析出 12 个差异蛋白,其中 8 个蛋白表达水平上升,4 个蛋白表达水平下降,包括ALAD、FGA(纤维蛋白原α链)、IGHV3-64D及IGHV3-38 等。主要涉及脂质与动脉粥样硬化、补体途径、金黄色葡萄球菌感染、NF-κB信号通路、流体剪切应力与动脉粥样硬化等信号通路。(4)ALAD、FGA、IGHV3-64D等 3 个蛋白靶点在特应性皮炎患者中的表达显著下调,而在培土清心颗粒治疗后显著上调。结论 差异表达蛋白ALAD、FGA、IGHV3-64D可能是培土清心颗粒治疗特应性皮炎的作用靶点,为进一步实验验证奠定了基础。
A Preliminary Proteomic Study of Peitu Qingxin Granules for the Treatment of Atopic Dermatitis
Objective A serum proteomic approach was used to explore the targets of action of Peitu Qingxin Granules(composed of Rhizoma Atractylodis Macrocephalae,Forsythiae Fructus,Imperatae Rhizoma,Pseudostellariae Radix,etc.)in the treatment of atopic dermatitis.Methods Five patients with atopic dermatitis were selected and treated with Peitu Qingxin Granules for 12 weeks,and five healthy volunteers were used as controls.The clinical core evaluation indexes of atopic dermatitis patients after treatment,including Eczema Area and Severity Index/Scoring Atopic Dermatitis(EASI/SCORAD),Pruritus Score,Patient-Oriented Eczema Measure(POEM),and quality of life index,were assessed.Serum samples were examined using data-independent acquisition-mass spectrometry(DIA-MS)technology,and serum differential proteins between atopic dermatitis patients and healthy people,as well as serum differential proteins in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules were screened according to P<0.05 and Fold Change>1.2.GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the differential proteins.Results(1)Compared with the pre-treatment period,the clinical core evaluation indexes of patients with atopic dermatitis,including the EASI/SCORAD,Pruritus Score,POEM,and quality-of-life index,were significantly improved after treatment,and the differences were all statistically significant(P<0.05,P<0.01).(2)A total of 28 differential proteins were analyzed in the healthy control group and atopic dermatitis group,of which 12 proteins expressions were increased and 16 proteins were decreased,including ALAD(δ-aminolevulinic acid dehydrogenase),LTA4H(leukotriene A-4 hydrolase),CA1(carbonic anhydrase 1),F11(coagulation factor XI),and LCP1(lymphocyte cytoplasmic protein 1),etc..The main signaling pathways involved are PI3K-AKT signaling pathway,lipids and atherosclerosis,ECM-receptor interaction,platelet activation,NF-κB signaling pathway,and neutrophil extracellular trap formation.(3)A total of 12 different proteins were analyzed in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules,of which 8 proteins were increased and 4 proteins were decreased,including ALAD,FGA(fibrinogen α-chain),IGHV3-64D,and IGHV3-38.They were mainly involved in signaling pathways such as lipids and atherosclerosis,complement pathway,Staphylococcus aureus infection,NF-κB signaling pathway,fluid shear stress and atherosclerosis.(4)The expressions of three protein targets including ALAD,FGA and IGHV3-64D,were significantly down-regulated in patients with atopic dermatitis and significantly up-regulated after treatment with Peitu Qingxin Granules.Conclusion The differentially expressed proteins ALAD,FGA and IGHV3-64D may be the action targets of Peitu Qingxin Granules in the treatment of atopic dermatitis,which lays the foundation for further experimental validation.

atopic dermatitisPeitu Qingxin GranulesproteomicsDIA-MSALADFGAIGHV3-64D

刘俊峰、张凯、莫秀梅、王赛娅、晏烽根、叶思琪、贾金靖、张瑜、陈达灿、于晓波

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省部共建中医湿证国家重点实验室/广州中医药大学第二附属医院,广东 广州 510120

河北大学生命科学学院,河北 保定 071002

粤港澳中医药与免疫疾病研究联合实验室,广东 广州 510120

蛋白质组学国家重点实验室/北京蛋白质组研究中心/国家蛋白质科学中心·北京(凤凰中心)/军事科学院军事医学研究院生命组学研究所,北京 102206

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特应性皮炎 培土清心颗粒 蛋白质组学 数据非依赖采集质谱 δ-氨基乙酰丙酸脱水酶 纤维蛋白原α链 IGHV3-64D

广东省重点领域研发计划项目省部共建中医湿证国家重点实验室项目省部共建中医湿证国家重点实验室项目广东省中医院中医药科学技术研究专项广东省科技创新战略专项(粤港澳联合实验室)项目广东省科技厅项目广州中医药大学"双一流"与高水平大学学科协同创新团队项目

2020B1111100010SZ2021ZZ39SZ2021ZZ17YN2021DB052020B12120300062021XK08

2024

中药新药与临床药理
广州中医药大学

中药新药与临床药理

CSTPCD北大核心
影响因子:0.908
ISSN:1003-9783
年,卷(期):2024.35(2)
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