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ObjectiveTo explore the anti-inflammatory effect of Duhuo Jishengtang （DHJST） on collagen-induced arthritis （CIA） model rats and its effect on the Toll-like receptor 2 （TLR2）/p38 mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） signaling pathway. MethodForty-eight male SD rats were randomly divided into the following six groups （n=8）： normal group， model group， methotrexate （MTX） group， low-dose DHJST （DHJST-L） group， medium-dose DHJST （DHJST-M） group， and high-dose DHJST （DHJST-H） group. The CIA model was established by injecting bovine type Ⅱ collagen into the rat tail root with the collagen antibody induction method. After model induction， rats were treated with drugs by gavage. The rats in the MTX group received MTX at 2.0 mg·kg-1， three times a week， and those in the DHJST groups received DHJST at 3.8， 7.6， 15.2 g·kg-1·d-1 for 28 days. The rats in the normal group and the model group were given the same dose of normal saline. The weight of the rats was recorded， and the paw swelling degree was observed. The arthritis index and immune organ index were measured， and the changes in the microcirculation indexes of the rats were detected with a microcirculation detector. Hematoxylin-eosin （HE） staining was used to detect the pathological morphologic changes in rat synovial tissues and the apoptosis rate of synovial cells was detected by flow cytometry to determine the therapeutic effect of DHJST on rheumatoid arthritis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the changes in serum levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-17A， and interferon-γ （IFN-γ）. The protein expression of TLR2， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， p38 MAPK， and p-p38 MAPK was detected by Western blot. ResultCompared with the normal group， the model group showed reduced body weight （P<0.01）， increased paw swelling degree， arthritis index， and immune organ index （P<0.01）， increased comprehensive microvascular score and vascular resistance （P<0.01）， significant hyperplasia of synovial tissues and massive infiltration of inflammatory cells as revealed by pathological sections， and up-regulated expression levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum， and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.01）. Compared with the model group， the DHJST groups showed increased body weight of rats （P<0.01）， decreased paw swelling degree， arthritis index， and immune organ index （P<0.05， P<0.01）， reduced comprehensive microvascular score and vascular resistance （P<0.05， P<0.01）， improved synovial histopathological injury， increased apoptosis rate of synovial cells （P<0.01）， and down-regulated levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum （P<0.05， P<0.01） and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.05， P<0.01）. ConclusionDHJST may alleviate the inflammatory reaction in CIA rats by regulating the TLR2/p38 MAPK/NF-κB signaling pathway， thus exerting its anti-rheumatoid arthritis effect.
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Pyroptosis is a newly discovered programmed cell death. It is an important natural immune response and has obvious anti-infection function. Studies have shown that pyroptosis plays an important role in the occurrence and development of rheumatoid arthritis. Traditional Chinese medicine（TCM） has unique advantages in the prevention and treatment of rheumatoid arthritis. How to guide TCM to effectively prevent and treat rheumatoid arthritis using pyroptosis theory is a new research hotspot in this field. This paper discussed the overview of pyroptosis theory，its mechanism， signal pathway，and application in the treatment of rheumatoid arthritis as well as the research on the activity of TCM based on pyroptosis theory. It was found that the occurrence of pyroptosis was related to Caspase-1-dependent classical inflammatory body pathway and Caspase-1-independent non classical inflammatory body pathway， and pyroptosis produced distinct regulatory effect on the occurrence，development and treatment of rheumatoid arthritis，which would provide a new strategy for the treatment of rheumatoid arthritis. Additionally，TCM recipes such as Miao ethnomedicine prescription Sidaxue and Duhuo Jishengtang， and a variety of effective components such as punicalagin and paeoniflorin monomer derivatives exerted anti-rheumatic and other biological activities by regulating pyroptosis. This provided a theoretical basis and research ideas for the in-depth study of pyroptosis theory and guiding the prevention and treatment of rheumatoid arthritis with TCM.
RESUMEN
Pyroptosis is a newly discovered programmed cell death. It is an important natural immune response and has obvious anti-infection function. Studies have shown that pyroptosis plays an important role in the occurrence and development of rheumatoid arthritis. Traditional Chinese medicine（TCM） has unique advantages in the prevention and treatment of rheumatoid arthritis. How to guide TCM to effectively prevent and treat rheumatoid arthritis using pyroptosis theory is a new research hotspot in this field. This paper discussed the overview of pyroptosis theory，its mechanism， signal pathway，and application in the treatment of rheumatoid arthritis as well as the research on the activity of TCM based on pyroptosis theory. It was found that the occurrence of pyroptosis was related to Caspase-1-dependent classical inflammatory body pathway and Caspase-1-independent non classical inflammatory body pathway， and pyroptosis produced distinct regulatory effect on the occurrence，development and treatment of rheumatoid arthritis，which would provide a new strategy for the treatment of rheumatoid arthritis. Additionally，TCM recipes such as Miao ethnomedicine prescription Sidaxue and Duhuo Jishengtang， and a variety of effective components such as punicalagin and paeoniflorin monomer derivatives exerted anti-rheumatic and other biological activities by regulating pyroptosis. This provided a theoretical basis and research ideas for the in-depth study of pyroptosis theory and guiding the prevention and treatment of rheumatoid arthritis with TCM.
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Objective:To observe the clinical efficacy of Duhuo Jishengtang combined with minimally invasive decompression of lumber spine in the treatment of degenerative lumbar spinal stenosis with kidney deficiency syndrome for more than 3 years. Method:Through a single-center parallel randomized controlled clinical trial， 63 patients with degenerative lumbar spinal stenosis who were hospitalized in Jiangsu Hospital of Traditional Chinese Medicine from October 2015 to April 2017 were observed for more than three years. Among them， there were 31 cases in the operation combined with traditional Chinese medicine group （observation group） and 32 cases in the operation combined with Celebrex and Mecobalamin group （control group）. Both groups were given routine treatment. The observation group was treated with Duhuo Jishengtang for 3 weeks， while the control group was treated with Celebrex and Mecobalamin for 3 weeks. Result:In the aspect of pain improvement， only 3 months after operation， the observation group was superior to the control group （P<0.05）， with no significant advantage at other time nodes during follow-up. During the 3-month follow-up and a longer period， it was confirmed that observation group had a significant advantage in improving lumbar function （P<0.01）. At the last follow-up， the good efficacy rate of observation group was 83.87% （26/31）， while the good efficacy rate of the control group was 62.5% （20/32）. There was no unstable performance in the last follow-up of the two groups. There was no statistically significant difference between two groups. Conclusion:The middle and long-term follow-up for minimally invasive decompression of lumber spine showed a satisfactory efficacy in the treatment of degenerative lumbar spinal stenosis， with no impact on the stability of the operative segments. For patients of lumbar spinal stenosis with kidney deficiency syndrome， Duhuo Jishengtang can promote the recovery of postoperative neurological function， and improve the good efficacy rate of clinical treatment， but with no obvious advantage in pain relieve after operation.