Objectives:To explore and summarize the beneficial effects of a traditional Chinese medicine preparation,Tripterygium glycosides tablets(TGT),in rheumatoid arthritis(RA)animal models of neovascularization,and to provi...Objectives:To explore and summarize the beneficial effects of a traditional Chinese medicine preparation,Tripterygium glycosides tablets(TGT),in rheumatoid arthritis(RA)animal models of neovascularization,and to provide a reference for future clinical applications and research on its pharmacologic mechanism.Methods:We searched the databases PubMed,Embase,Web of Science,Chinese National Knowledge Infrastructure,VIP,Wan Fang and SinoMed(China Biomedical Document Service System)to identify studies of TGT with outcome indicators of angiogenesis-related factors that were published before April2020.Subgroup analysis and meta-regression were performed for dosage and duration of TGT.Statistical tests and subgroup analysis were conducted using RevMan 5.3,and meta-regression and sensitivity analysis were conducted using STATA/SE 15.0.Results:Fourteen studies of TGT in RA rats were included in this analysis.Treatment with TGT significantly reduces synovial microvessel density and the expression of vascular endothelial growth factor(VEGF),VEGF receptor 2,hypoxia inducible factor a,c-Fos,c-Jun,angiopoietin-1 and angiopoietin-2 compared with control groups(P<.05).Subgroup analysis did not show a significant association of the mRNA levels of VEGF in synovium,assessed using quantitative real-time PCR,with duration or dosage of TGT.Meta-regression analysis also indicated that the effects of dosage and duration were not significantly associated with differences in VEGF mRNA levels.Sensitivity analysis on VEGF m RNA levels did not fundamentally change the results.Conclusions:TGT can reduce synovial neovascularization by decreasing synovial microvessel density and expression of VEGF,VEGF receptor 2,hypoxia-inducible factor a,c-Fos,c-Jun,Ang-1 and Ang-2,thereby suppressing pannus formation and bone destruction in rat models of RA.Additional well-designed studies are required to confirm these findings.展开更多
Rheumatoid arthritis(RA)is a common autoimmune disease characterized by progressive joint inflammation and destruction,deformity,loss of mobility,and permanent disability.Although the cellular and molecular mechanisms...Rheumatoid arthritis(RA)is a common autoimmune disease characterized by progressive joint inflammation and destruction,deformity,loss of mobility,and permanent disability.Although the cellular and molecular mechanisms involved in RA are understood in detail,no drugs or therapies can completely cure RA.Many long-term efforts have been directed towards a better understanding of RA pathogenesis and the development of new classes of therapeutics.Thus,the ongoing elucidation of pathogenic events underlying RA mostly relies on studies of animal models.Herein,we comprehensively review and discuss the characteristics,challenges,and unresolved of issues of various experimental models of RA to provide a basis and reference for the rational selection of experimental RA models for basic investigations into traditional Chinese medicine(TCM).展开更多
Objective:To establish a collagen type II-induced rat model of rheumatoid arthritis(RA)presenting characteristics of the human form of the traditional Chinese syndrome pattern of toxic heat-stasis painful obstruction(...Objective:To establish a collagen type II-induced rat model of rheumatoid arthritis(RA)presenting characteristics of the human form of the traditional Chinese syndrome pattern of toxic heat-stasis painful obstruction(bi zheng;arthromyodynia)as well as pathologic features of active RA.The Chinese herbal medicine Tengmei decoction was used to validate the animal model.Methods:Ninety specific pathogen free Sprague-Dawley rats were randomly divided into a normal group of 6 rats and a model group of 84 rats.To establish the rat model of collageninduced arthritis(CIA),bovine type II collagen in complete Freund’s adjuvant was injected into the model group rats as a priming dose(Day 0)and boosting dose(Day 9).Changes in arthritic index(AI)scores,including limb swelling,were monitored.Thereafter,24 successfullyestablished CIA rats were randomly assigned to 4 groups with 6 animals each:model,positive control drug,high-dose traditional Chinese herbal medicine,and traditional Chinese herbal medicine.A blank control group of 6 rats was included.After 12 weeks of intervention with Tengmei decoction,articular synovial tissue and serum specimens were collected to detect interleukin-2(IL-2)and IL-17 transcription and protein expression levels.展开更多
Expansion of diagnostic criteria for rheumatoid arthritis and deletion of exceptions increases sensitivity, but at the expense of specificity.Two decades later, modification of criteria included the caveat: "abse...Expansion of diagnostic criteria for rheumatoid arthritis and deletion of exceptions increases sensitivity, but at the expense of specificity.Two decades later, modification of criteria included the caveat: "absence of an alternative diagnosis that better explains the synovitis."That puts great faith in the diagnostic skills of the evaluating individual and their perspectives of disease.The major confounding factor appears to be spondyloarthropathy, which shares some characteristics with rheumatoid arthritis.Recognition of the latter on the basis of marginally distributed and symmetrical polyarticular erosions, in absence of axial(odontoid disease excepted) involvement requires modification to avoid failure to recognize a different disease, spondyloarthropathy.Skeletal distribution, pure expression of disease in natural animal models and biomechanical studies clearly rule out peripheral joint fusion(at least in the absence of corticosteroid therapy) as a manifestation of rheumatoid arthritis.Further, such studies identity predominant wrist and ankle involvement as characteristic of a different disease, spondyloarthropathy.It is important to separate the two diagnostic groups for epidemiologic study and for clinical diagnosis.They certainly differ in their pathophysiology.展开更多
Backgroud Interleukin 16 （IL-1β） is the principal mediator in the pathogenesis of rheumatoid arthritis. Continuous injection of interleukin 1β （IL-1β） into the knee articular cavities of anamals can induce mode...Backgroud Interleukin 16 （IL-1β） is the principal mediator in the pathogenesis of rheumatoid arthritis. Continuous injection of interleukin 1β （IL-1β） into the knee articular cavities of anamals can induce models that resemble rheumatoid arthritis. The objective of this study was to evaluate the feasibility of local recombinant retrovirus viral interleukin 10 （rRV-vlL-10） gene transfer treatment of a rabbit model of arthritis induced by IL-16. Methods An hlL-1β-induced rabbit rheumatoid arthritis model was established using the MFG-hlL-1β-neo-HIG-82 cell line, which is capable of continuous secretion of hlL-1β. After transfecting the rabbit synovial fibroblast cell line （MFG-hlL-1β-neo-HIG-82） with rRV-vlL-10, G418 was then added to identify the positive clone. The rRV-vlL-10 positive clone was injected into the established rabbit rheumatoid arthritis model through intra-articular injection. Successful gene transfer was determined by reverse transcripUon-polymerase chain reaction （RT-PCR） and immunohistochemistry. The levels of IL-1β before and after treatment were determined by enzyme- linked immunosorbent assay. Results Retrovirus vector was an effective vector both to synoviocytes in vitro and synovium tissue in vivo as confirmed by RT-PCR and immunohistochemistry. The rabbit arthritis model treated with rRV-vlL-10 showed a dramatic remission of arthritis and a decline in the level of cytokines such as IL-1β. Conclusions Retrovirus-mediated transfecUon of vlL-10 successfully transferred the gene into rabbit synovium ex vivo and was able to suppress intra-articular inflammation response to IL-1β.展开更多
The RA mixture is composed of Tripterygium wilfordii (TW) and other Chinese medicinalherbs with effect of expelling Wind, activating blood circulation, invigorating the Kidney and Qi . The authorstreated rheumatoid ar...The RA mixture is composed of Tripterygium wilfordii (TW) and other Chinese medicinalherbs with effect of expelling Wind, activating blood circulation, invigorating the Kidney and Qi . The authorstreated rheumatoid arthritis ( RA) patients with RA mixture and compared it with D-Penicillamine as ocntrol .The two group's therapeutical effect is similar ( P >0. 05) , but side effect occuring ratio in treatment groupwas obviously lower than that of control group ( P<0 . 01 ) . After treatment with RA mixture, the patient's hu-man lymphocytic antigen-degenerative reaction ( HLA-DR+ ) cell, CD4/CD8 ratio were reduced and auto-mixed lymphocytic reaction ( AMLR) level enhanced ( P < 0. 05) . The results of animal experiment showedthat swelling of rheumatoid arthritis model mouse's joint could be reduced by both RA mixture and TW. Com-paring with TW. RA mixture had stronger effect in controlling the inflammation of synovial cell and fibroid de-generation of fibrocytes. At the same time, RA mixture had stronger effect in protecting immune organ fromatrophy and maintaining functions of cellular immunity. All these suggest that RA mixture can reduce the syn-droms of RA by improving distribution of T Iymphocyte subsets and functions of cellular immunity. The Chinesemedicinal herbs for reinforcing Kidney, supplementing Qi , activating blood circulation and expelling evil windin the RA mixture could enhance TW's therapeutical effect and reduce it's side effect.展开更多
基金the National Natural Science Foundation of China(No.81660836)。
文摘Objectives:To explore and summarize the beneficial effects of a traditional Chinese medicine preparation,Tripterygium glycosides tablets(TGT),in rheumatoid arthritis(RA)animal models of neovascularization,and to provide a reference for future clinical applications and research on its pharmacologic mechanism.Methods:We searched the databases PubMed,Embase,Web of Science,Chinese National Knowledge Infrastructure,VIP,Wan Fang and SinoMed(China Biomedical Document Service System)to identify studies of TGT with outcome indicators of angiogenesis-related factors that were published before April2020.Subgroup analysis and meta-regression were performed for dosage and duration of TGT.Statistical tests and subgroup analysis were conducted using RevMan 5.3,and meta-regression and sensitivity analysis were conducted using STATA/SE 15.0.Results:Fourteen studies of TGT in RA rats were included in this analysis.Treatment with TGT significantly reduces synovial microvessel density and the expression of vascular endothelial growth factor(VEGF),VEGF receptor 2,hypoxia inducible factor a,c-Fos,c-Jun,angiopoietin-1 and angiopoietin-2 compared with control groups(P<.05).Subgroup analysis did not show a significant association of the mRNA levels of VEGF in synovium,assessed using quantitative real-time PCR,with duration or dosage of TGT.Meta-regression analysis also indicated that the effects of dosage and duration were not significantly associated with differences in VEGF mRNA levels.Sensitivity analysis on VEGF m RNA levels did not fundamentally change the results.Conclusions:TGT can reduce synovial neovascularization by decreasing synovial microvessel density and expression of VEGF,VEGF receptor 2,hypoxia-inducible factor a,c-Fos,c-Jun,Ang-1 and Ang-2,thereby suppressing pannus formation and bone destruction in rat models of RA.Additional well-designed studies are required to confirm these findings.
基金funding support from the Science and Technology Innovation Program of Hunan Province(No.XKJ[2021]43-2021RC4035)supported by the Hunan Furong Distinguished Scholar Program(No.XJT[2020]58)the Chinese Academy of Engineering Academician LIU Liang’s Workstation of Hunan(No.XKXT[2020]34)。
文摘Rheumatoid arthritis(RA)is a common autoimmune disease characterized by progressive joint inflammation and destruction,deformity,loss of mobility,and permanent disability.Although the cellular and molecular mechanisms involved in RA are understood in detail,no drugs or therapies can completely cure RA.Many long-term efforts have been directed towards a better understanding of RA pathogenesis and the development of new classes of therapeutics.Thus,the ongoing elucidation of pathogenic events underlying RA mostly relies on studies of animal models.Herein,we comprehensively review and discuss the characteristics,challenges,and unresolved of issues of various experimental models of RA to provide a basis and reference for the rational selection of experimental RA models for basic investigations into traditional Chinese medicine(TCM).
文摘Objective:To establish a collagen type II-induced rat model of rheumatoid arthritis(RA)presenting characteristics of the human form of the traditional Chinese syndrome pattern of toxic heat-stasis painful obstruction(bi zheng;arthromyodynia)as well as pathologic features of active RA.The Chinese herbal medicine Tengmei decoction was used to validate the animal model.Methods:Ninety specific pathogen free Sprague-Dawley rats were randomly divided into a normal group of 6 rats and a model group of 84 rats.To establish the rat model of collageninduced arthritis(CIA),bovine type II collagen in complete Freund’s adjuvant was injected into the model group rats as a priming dose(Day 0)and boosting dose(Day 9).Changes in arthritic index(AI)scores,including limb swelling,were monitored.Thereafter,24 successfullyestablished CIA rats were randomly assigned to 4 groups with 6 animals each:model,positive control drug,high-dose traditional Chinese herbal medicine,and traditional Chinese herbal medicine.A blank control group of 6 rats was included.After 12 weeks of intervention with Tengmei decoction,articular synovial tissue and serum specimens were collected to detect interleukin-2(IL-2)and IL-17 transcription and protein expression levels.
文摘Expansion of diagnostic criteria for rheumatoid arthritis and deletion of exceptions increases sensitivity, but at the expense of specificity.Two decades later, modification of criteria included the caveat: "absence of an alternative diagnosis that better explains the synovitis."That puts great faith in the diagnostic skills of the evaluating individual and their perspectives of disease.The major confounding factor appears to be spondyloarthropathy, which shares some characteristics with rheumatoid arthritis.Recognition of the latter on the basis of marginally distributed and symmetrical polyarticular erosions, in absence of axial(odontoid disease excepted) involvement requires modification to avoid failure to recognize a different disease, spondyloarthropathy.Skeletal distribution, pure expression of disease in natural animal models and biomechanical studies clearly rule out peripheral joint fusion(at least in the absence of corticosteroid therapy) as a manifestation of rheumatoid arthritis.Further, such studies identity predominant wrist and ankle involvement as characteristic of a different disease, spondyloarthropathy.It is important to separate the two diagnostic groups for epidemiologic study and for clinical diagnosis.They certainly differ in their pathophysiology.
文摘Backgroud Interleukin 16 （IL-1β） is the principal mediator in the pathogenesis of rheumatoid arthritis. Continuous injection of interleukin 1β （IL-1β） into the knee articular cavities of anamals can induce models that resemble rheumatoid arthritis. The objective of this study was to evaluate the feasibility of local recombinant retrovirus viral interleukin 10 （rRV-vlL-10） gene transfer treatment of a rabbit model of arthritis induced by IL-16. Methods An hlL-1β-induced rabbit rheumatoid arthritis model was established using the MFG-hlL-1β-neo-HIG-82 cell line, which is capable of continuous secretion of hlL-1β. After transfecting the rabbit synovial fibroblast cell line （MFG-hlL-1β-neo-HIG-82） with rRV-vlL-10, G418 was then added to identify the positive clone. The rRV-vlL-10 positive clone was injected into the established rabbit rheumatoid arthritis model through intra-articular injection. Successful gene transfer was determined by reverse transcripUon-polymerase chain reaction （RT-PCR） and immunohistochemistry. The levels of IL-1β before and after treatment were determined by enzyme- linked immunosorbent assay. Results Retrovirus vector was an effective vector both to synoviocytes in vitro and synovium tissue in vivo as confirmed by RT-PCR and immunohistochemistry. The rabbit arthritis model treated with rRV-vlL-10 showed a dramatic remission of arthritis and a decline in the level of cytokines such as IL-1β. Conclusions Retrovirus-mediated transfecUon of vlL-10 successfully transferred the gene into rabbit synovium ex vivo and was able to suppress intra-articular inflammation response to IL-1β.
文摘The RA mixture is composed of Tripterygium wilfordii (TW) and other Chinese medicinalherbs with effect of expelling Wind, activating blood circulation, invigorating the Kidney and Qi . The authorstreated rheumatoid arthritis ( RA) patients with RA mixture and compared it with D-Penicillamine as ocntrol .The two group's therapeutical effect is similar ( P >0. 05) , but side effect occuring ratio in treatment groupwas obviously lower than that of control group ( P<0 . 01 ) . After treatment with RA mixture, the patient's hu-man lymphocytic antigen-degenerative reaction ( HLA-DR+ ) cell, CD4/CD8 ratio were reduced and auto-mixed lymphocytic reaction ( AMLR) level enhanced ( P < 0. 05) . The results of animal experiment showedthat swelling of rheumatoid arthritis model mouse's joint could be reduced by both RA mixture and TW. Com-paring with TW. RA mixture had stronger effect in controlling the inflammation of synovial cell and fibroid de-generation of fibrocytes. At the same time, RA mixture had stronger effect in protecting immune organ fromatrophy and maintaining functions of cellular immunity. All these suggest that RA mixture can reduce the syn-droms of RA by improving distribution of T Iymphocyte subsets and functions of cellular immunity. The Chinesemedicinal herbs for reinforcing Kidney, supplementing Qi , activating blood circulation and expelling evil windin the RA mixture could enhance TW's therapeutical effect and reduce it's side effect.
