Abstract
Observation ECA’s treatment effects in Adjuvant arthritis rats and relative mechanisms. The rat model of arthritis was established by subcutaneous injection of 0.2 mL Freund’s complete adjuvant. After model success, giving different ECA concentrations (25 mg/kg, 50 mg/kg and 100 mg/kg) to rats by ig methods and continued to 28 days. Measuring thymus and spleen index; observation histopathological morphology of rat joint by HE and Masson staining, and Inflammatory cells, synovial hyperplasia, oochas score and degree of fibrosis were detected semi quantitatively. The relative gene and protein expressions were measured by RT-PCR and Western blot. Compared with Normal group, Inflammatory cells, synovial hyperplasia, fibrosis and oochas score increased significantly in Model group (P<0.01, respectively); COX-1, COX-2, TNF-α, IL-1β, IL-6 and IL-17 mRNA expression were significantly up-regulation (P<0.01); AMPK, Beclin1 and ATG12 mRNA and protein expressions were significantly down-regulation (P<0.01, respectively). Compared with Model group, The inflammatory cells, the degree of fibrosis, the proliferation of synovial tissue and OOCHAS score decreased significantly in Middle and High groups (P<0.01, respectively); Thymus index significantly depressed in Low, Middle and High groups (P<0.01, respectively); spleen index were significantly down-regulation in Middle and High groups (P<0.05 or P<0.01); COX-2, TNF-α and IL-17 mRNA expression was significantly down-regulation (P<0.05), IL-1βand IL-6 mRNA expression were significantly depressed in Middle and High groups (P<0.05 or P<0.01); AMPK, Beclin1, LC3-II, ATG5 and ATG7 mRNA expressions were significantly up-regulation in Middle and High groups (P<0.05 or P<0.01); mTOR gene expression was significantly down-regulation (P<0.05), ATG12 mRNA expression was significantly up-regulation (P<0.01) in High group; AMPK, Beclin1, LC3-II, ATG5 and ATG7 protein expressions were significantly increased in High group (P<0.05 or P<0.01), mTOR protein expression were significantly down-regulation and ATG12 protein expression were significantly up-regulation in Low, Middle and High groups (P<0.05 or P<0.01, respectively). ECA can inhibit the inflammatory response in adjuvant arthritis rats, and its mechanism may be related to promoting autophagy of synovial cells.
Highlights
Rheumatoid arthritis (RA) is a typical chronic inflammation characterized by systemic autoimmune abnormalities (Weyand & Goronzy, 2021)
According to the results of HE staining (Figure 1), rats in the Normal group displayed no abnormality in the joint structure, cartilage lining, joint space and bone tissue morphology, with no inflammatory cell infiltration in synovium; while in the Model group, it was observed with significant abnormality in the joint tissue, obvious proliferation of the synovium, infiltration
Owing to the insufficient glycolytic enzyme of enzyme fructose-6-phosphate, 2-Kinase/fructose-2,6bisphosphatase, RA patients may have low glycolytic flux in T cells and ATP deficiency in vivo (Silva et al, 2019; Custers et al, 2007). It may further reduce the ratio of adenosine monophosphate (AMP) to ATP, activate the autophagy-related AMPK-PI3K-mammalian target of rapamycin (mTOR) signal transduction pathway in patients, and result in the abnormal expressions of genes and proteins related to this pathway (Luo et al, 2018; Larabi et al, 2020; Wang et al, 2019; Hwang et al, 2020)
Summary
Rheumatoid arthritis (RA) is a typical chronic inflammation characterized by systemic autoimmune abnormalities (Weyand & Goronzy, 2021). In RA patients, owing to the insufficient glycolytic enzymes in vivo, there may be a low glycolytic flux of T cells and deficiency of ATP (Silva et al, 2019). Due to the decreased ratio of AMP and ATP, there may be an activation in the autophagy related signal transduction pathway, accompanied by abnormal expressions of genes and proteins in this pathway. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in this pathway are recognized to be the key genes and proteins to initiate autophagy pathway. In view of the above content, it is suggested that abnormality in the autophagy pathway in RA patients may be one of the causes inducing the pathogenesis of RA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
