首页|基于转录组学探索瘀血痹片治疗类风湿关节炎滑膜炎症的作用机制

基于转录组学探索瘀血痹片治疗类风湿关节炎滑膜炎症的作用机制

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基于转录组学分析瘀血痹片(Yuxuebi Tablets，YXB)治疗类风湿关节炎(rheumatoid arthritis，RA)滑膜炎症的机制。运用转录组学测序技术检测正常组、胶原诱导型关节炎(collagen-induced arthritis，CIA)模型组、YXB组大鼠关节组织的基因表达谱，共同差异表达基因进行基因功能注释(Gene Ontology，GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析。通过OMIM、GeneCards数据库检索RA滑膜炎症疾病的相关靶点;通过Venny 2。1 平台对YXB作用靶点和RA滑膜炎症疾病靶点取交集，对交集靶点进行GO功能及KEGG通路富集分析。运用免疫组化法检测大鼠关节组织中炎症因子白细胞介素-1β(interleukin-1β，IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)蛋白表达情况，并运用Western blot法检测磷脂酰肌醇 3-激酶(phosphatidylinositol 3-kinase，PI3K)/蛋白激酶B(Akt)信号通路关键蛋白的表达水平。正常组vs模型组、模型组vs YXB组差异基因取交集得到明显差异基因 2 058 个。通过OMIM、GeneCards数据库检索RA滑膜炎症相关靶点 1 102 个，与YXB组明显差异基因取交集后得到204 个交集靶点，主要涉及免疫反应(immune response)、信号传导(signal transduction)、炎症反应(inflammatory response)等生物过程，细胞质膜(plasma membrane)、细胞外间隙(extracellular space)、胞外区(extracellular region)等细胞组分，蛋白结合(protein binding)、相同蛋白结合(identical protein binding)、受体结合(receptor binding)等分子功能，主要富集到PI3K/Akt、细胞因子受体相互作用、Janus激酶/信号转导和转录激活因子(JAK/STAT)等信号通路。Western blot验证结果显示，YXB低、中、高剂量均能不同程度抑制大鼠关节组织中PI3K/Akt信号通路关键蛋白的表达水平，并呈现剂量依赖性。免疫组化进一步确认，YXB不仅能抑制CIA大鼠关节滑膜组织中炎症因子IL-1β和TNF-α水平，而且也能抑制p-Akt蛋白的表达。综上，该研究通过转录组学挖掘YXB抑制滑膜炎症缓解RA病情进展的关键机制，并通过系列验证发现与其抑制PI3K/Akt信号通路有关。
Mechanism of Yuxuebi Tablets in treating synovial inflammation in rheumatoid arthritis based on transcriptomics
This study investigated the mechanism of Yuxuebi Tablets(YXB)in the treatment of synovial inflammation in rheuma-toid arthritis(RA)based on transcriptomic analysis.Transcriptome sequencing technology was employed to analyze the gene expression profiles of joint tissues from normal rats,collagen-induced arthritis(CIA)rats(an RA model),and YXB-treated rats.Common diffe-rentially expressed genes(DEGs)were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.RA synovial inflammation-related target genes were retrieved from the OMIM and GeneCards databases.Venny 2.1 software was used to identify the intersection of YXB target genes and RA synovial inflammation-related target genes,and GO and KEGG enrichment analyses were performed on the intersecting target genes.Immunohistochemistry was used to assess the protein ex-pression levels of the inflammatory factors interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in rat joint tissues.Western blot analysis was employed to measure the expression levels of key proteins in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.A total of 2 058 DEGs were identified by intersecting the genes from the normal group vs model group and the model group vs YXB treatment group.A search in OMIM and GeneCards databases yielded 1 102 RA synovial inflammation-related target genes.After intersecting with the DEGs in the YXB treatment group,204 intersecting target genes were identified,primarily in-volving biological processes such as immune response,signal transduction,and inflammatory response;cellular components including plasma membrane,extracellular space,and extracellular region;molecular functions like protein binding,identical protein binding,and receptor binding.These target genes were mainly enriched in signaling pathways such as PI3K/Akt,cytokine-cytokine receptor in-teraction,and Janus kinase/signal transducer and activator of transcription(JAK/STAT).Western blot results showed that YXB at low,medium,and high doses could significantly inhibit the expression levels of key proteins in the PI3K/Akt signaling pathway in rat joint tissues in a dose-dependent manner.Immunohistochemistry further confirmed these findings,showing that YXB not only sup-pressed the protein expression levels of the inflammatory factors IL-1β and TNF-α in the joint synovial tissues of CIA rats,but also inhibi-ted p-Akt protein expression.In conclusion,this study used transcriptomic analysis to uncover the key mechanisms of YXB in inhibiting synovial inflammation and alleviating the progression of RA,with a focus on its role in suppressing the PI3K/Akt signaling pathway.

Yuxuebi Tabletsrheumatoid arthritissynovial inflammationtranscriptomicsPI3K/Akt signaling pathway

张昕卓、陶雪莹、黄凤玉、祝盼盼、袁蓓、陈沛萍、孔祥英、林娜、苏晓慧

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中国中医科学院 中药研究所, 北京 100700

瘀血痹片 类风湿关节炎 滑膜炎症 转录组学 PI3K/Akt信号通路

国家自然科学基金面上项目中央级公益性科研院所基本科研业务费专项中央级公益性科研院所基本科研业务费专项中国中医科学院中药研究所技术研发项目中国中医科学院中药研究所技术研发项目

82174042ZXKT21016ZXKT200142019031620200326

2024

10.19540/j.cnki.cjcmm.20230915.402

中国中药杂志
中国药学会

中国中药杂志

CSTPCD北大核心
影响因子：1.718
ISSN：1001-5302
年,卷(期)：2024.49(6)
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