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益肾达络饮对复发缓解型多发性硬化患者缺氧诱导因子-1α和细胞因子表达的影响OA北大核心CSTPCD

Effects of Yishen Daluo Decoction on the serum levels of the glycolysis-related protein HIF-1α and cytokines in patients with relapsing-remitting multiple sclerosis

中文摘要英文摘要

目的 分析复发缓解型多发性硬化(RRMS)患者中药复方益肾达络饮治疗前后血清糖酵解相关蛋白和细胞因子表达变化及其与临床特征的相关性,探讨益肾达络饮对多发性硬化患者的免疫调节作用机制.方法 回顾性选取2018年5月—2022年1月就诊于北京中医药大学东直门医院多发性硬化专病门诊的28例RRMS患者作为RRMS组,并对其中13例患者益肾达络饮治疗前后配对样本(益肾达络饮治疗前组和益肾达络饮治疗后组)进行比较,同时招募性别及年龄匹配的20名健康者作为健康对照组,采集所有受试者的临床信息,以扩展残疾量表(EDSS)评分评估RRMS患者神经功能损伤情况,采用酶联免疫吸附测定技术和SP-X多重细胞因子分析技术检测受试者血清缺氧诱导因子-1α(HIF-1α)和白细胞介素(IL)-1β、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12p70、IL-22、γ干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)10种细胞因子水平,利用Spearman相关性分析观察RRMS患者血清HIF-1α和细胞因子相关性,HIF-1α和细胞因子与患者病程、发作次数、EDSS评分的相关性.结果 与健康对照组比较,RRMS组患者血清HIF-1α、IL-4、IL-6、IL-8、IL-10、IL-12p70、IFN-γ、TNF-α水平明显升高,差异具有统计学意义(P<0.05).与益肾达络饮治疗前组比较,益肾达络饮治疗后组患者血清HIF-1α、IL-4、IL-6、IL-12p70水平均明显降低,差异有统计学意义(P<0.05).Spearman 相关性分析,RRMS 组患者血清 HIF-1α 水平与 IL-6(r=0.452,P=0.016)和TNF-α(r=0.524,P=0.004)水平呈正相关,IFN-γ水平与EDSS评分呈负相关(r=-0.423,P=0.025),IL-4水平与病程呈负相关(r=-0.385,P=0.043),TNF-α水平与病程呈正相关(r=0.397,P=0.037).结论 中药复方益肾达络饮对RRMS免疫失衡的调节作用机制,可能与其降低RRMS患者血清糖酵解相关蛋白HIF-1α和多种炎性细胞因子水平相关.

Objective We aimed to assess the serum levels of the glycolysis-related protein hypoxia-inducible factor-1α(HIF-1α)and cytokines in patients with relapsing-remitting multiple sclerosis(RRMS)before and after treatment with the traditional Chinese medicine Yishen Daluo Decoction,as well as their correlation with clinical parameters,and explore the immune regulatory mechanism of Yishen Daluo Decoction on multiple sclerosis.Methods Twenty-eight patients with RRMS in remission recruited from May 2018 to January 2022 in the Multiple Sclerosis Clinic at Dongzhimen Hospital,Beijing University of Chinese Medicine were retrospectively included.Comparisons were made with paired samples from 13 of them before and after Yishen Daluo Decoction treatment.A total of 20 gender-and age-matched healthy controls(HCs)were also recruited.Clinical information was collected from all of the subjects,and the neurological impairments of RRMS patients were assessed with the Expanded Disability Status Scale(EDSS)score.ELISA and SP-X multiplex cytokine assays were used to measure the serum levels of HIF-1 α and 10 cytokines(IL-1β,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-22,IFN-γ,and TNF-α),respectively.Spearman's method was used to analyze the correlation between the serum levels of HIF-1α and cytokines,and the correlation between the serum levels of HIF-1α and cytokines and patients'clinical indicators,including disease duration,the number of attacks,and the EDSS score.Results Serum HIF-1α,IL-4,IL-6,IL-8,IL-10,IL-12p70,IFN-γ,and TNF-α levels in the RRMS group were significantly higher than those in the HC group(P<0.05).Serum levels of HIF-1α,IL-4,IL-6,and IL-12p70 in the Yishen Daluo Decoction-pre group were significantly higher than those in the Yishen Daluo Decoction-post group(P<0.05).In addition,the serum HIF-1α level was positively correlated with IL-6(r=0.452,P=0.016)and TNF-α(r=0.524,P=0.004)levels in patients with RRMS.The IFN-γ level was negatively correlated with the EDSS score(r=-0.423,P=0.025),the IL-4 level was negatively correlated with disease duration(r=-0.385,P=0.043),and the TNF-α level was positively correlated with disease duration(r=0.397,P=0.037).Conclusion The regulatory mechanism of Yishen Daluo Decoction on immune imbalance in RRMS may be related to its ability to reduce the serum levels of the glycolysis-related protein HIF-1α in RRMS patients.It is also related to the levels of various inflammatory cytokines.

刘佳;关晓睿;张靖泽;杨琦;芮一峰;高颖

北京中医药大学东直门医院 北京 100700||北京中医药大学中医脑病研究院北京中医药大学东直门医院 北京 100700

中医学

益肾达络饮多发性硬化缺氧诱导因子-1α糖酵解相关蛋白细胞因子

Yishen Daluo Decoctionmultiple sclerosishypoxia-inducible factor-1αglycolysis-related proteincytokine

《北京中医药大学学报》 2024 (001)

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国家自然科学基金项目(No.82205034);中央高校基本科研业务费专项资金项目(No.2023-JYB-JBQN-017);北京市自然科学基金项目(No.7222114);中医药传承与创新"百千万"人才工程(岐黄工程)项目(国中医药人教发[2018]12号)National Natural Science Foundation of China(No.82205034);Fundamental Research Funds for the Central Universities(No.2023-JYB-JBQN-017);Beijing Natural Science Foundation(No.7222114);Chinese Medicine Inheritance and Innovation Talent Project Leading Talent Support Program of National Traditional Chinese Medicine(No.[2018]12)

10.3969/j.issn.1006-2157.2024.01.003

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