Exploring biological connotation of blood stasis syndrome of rheumatoid arthritis and establishment of improved animal models based on syndrome-symptom mapping
10.16438/j.0513-4870.2023-0529
- VernacularTitle:基于症状映射的类风湿关节炎瘀血阻络证生物内涵研究及其病证结合动物模型建立和评价
- Author:
Wen-jia CHEN
1
;
Tao LI
2
;
Ming-zhu XU
2
;
Xun GONG
3
;
Wei-xiang LIU
3
;
Pei-hao LI
4
;
Quan JIANG
3
;
Wei LIU
4
;
Xia MAO
1
;
Xin LI
1
;
Hai-yu XU
1
;
Na LIN
1
;
Yan-qiong ZHANG
1
Author Information
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
2. School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China
3. Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
4. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
- Publication Type:Research Article
- Keywords:
rheumatoid arthritis;
blood stasis syndrome;
transcriptomics;
eighted gene co-expression network analysis;
syndrome-symptom mapping;
combination of disease and syndrome
- From:
Acta Pharmaceutica Sinica
2023;58(8):2434-2441
- CountryChina
- Language:Chinese
-
Abstract:
Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.
