Comparison of Three Experimental Models for Rat Osteoarthritis Induction

Background: Osteoarthritis is a slowly progressive and debilitating disease with high prevalence in adult population. Knee is one of the joints most affected by this disorder. There are several models for animals’ osteoarthritis induction, however it is not identified any paper that compares these techniques. The present study was aimed to define the most appropriate model for rats osteoarthritis induction. Material and Methods: 40 Wistar rats were distributed into 4 groups of 10 animals each: normality group (NG);meniscectomy group (MG);quinolone group (QG) and iodoacetate group (IG). Radiographic images of the rat’s knees were analyzed as well as the amount of chondrocytes in the epiphyseal and articular cartilage. Results: In the radiographic analysis, there was a low correlation between the raters. Regarding the amount of chondrocytes in the epiphyseal cartilage, it was noticed that the IG and QG groups had fewer chondrocytes than NG, in contrast to MG that reported similar results to normality (p > 0.05). There was no significant difference between IG and QG groups (p > 0.05). Regarding the amount of chondrocytes in articular cartilage, it was noticed that the IG group showed fewer chondrocytes than NG (p 0.05). There was no significant difference between QG and MG groups (p > 0.05). Conclusion: Intraarticular injection of iodoacetate in rats is the model with greatest effect on reduction of chondrocytes amount.

Structural Changes in Vertebrae of Mice Based on Experimental Model of Rheumatoid Arthritis

Studies have shown that autoimmunity causes pathogenesis of more than 100 diseases. Among these diseases, approximately 1-2% of the world’s population has rheumatoid arthritis disease, which is a chronic disease that affects 45 out of every 3000 people who have autoimmune diseases. The aim of this research is to address the possible treatment of rheumatoid arthritis disease by comparing and contrasting the effectiveness and influence that treatments have on treating the disease. This study will be conducted by inducing the following treatments: ibuprofen and Boigor-10 on model animal subjects (mice) to determine the outcomes of the treatment. We will assess the outcomes by investigate the structural changes on vertebrae and joints of these subjects and the clinical manifestation score of each treatment. We hypothesize that these treatments will improve the treatment of rheumatoid arthritis disease. Furthermore, we hope that this research contributes to further understanding autoimmune disease and promotes proper treatment of the disease.

Effect of Triptolide on Expression of Receptor Activator of Nuclear Factor-κB Ligand in Rat Adjuvant Induced Arthritis

The effect of triptolide （TP） on the expression of receptor activator of nuclear factor-κB ligand （RANKL） and osteoprotegerin （OPG） was explored in rat adjuvant induced arthritis （AA）. AA was induced in Wistar rats. Arthritis rats were treated with TP and methotrexate （MTX） at the onset （day 9） of arthritis. On the peak of arthritis （day 24）, the expression of RANKL and OPG protein in the joints and RANKL mRNA in peripheral blood mononuclear cells （PBMC） was detected. TNF-α and IL-1β levels in peripheral blood were determined. Bone erosion scores were also evaluated. The results showed that bone erosion scores in TP and MTX groups were lower than in AA group （.P〈0.01） ; The expression levels of RANKL in the synovium （P〈0.01） and bone （P〈0.05）, and OPG level in synovium （P〈0.05） were lower in TP group than in AA group （P〈0.05）. In TP group, the expression levels of RANKL mRNA and TNF-α, IL-1β in PBMC were lower than in AA group （all P〈0.01）. It was concluded that TP could inhibit rat adjuvant arthritis bone erosion by suppressing the expression of RANKL.

Effects of Moxibustion on the Paw Swelling and Pain Threshold in Rats with Experimental Arthritis

Objective： To observe and compare the effects of mild moxibustion and Chinese medicine on the paw edema and pain threshold in rats with experimental arthritis. Methods： Forty-six male Wistar rats were randomly divided into 5 groups, a control group （10 rats）, a model group （9 rats）, a Chinese medicine （CM） group （9 rats）, a moxibustion group （9 rats） and a Western medicine （WM） group （9 rats）. Except rats in the control group, rats in the other four groups were established to be arthritis model by cold stimulation and Freund＇s adjuvant. After modeling, rats in the control group and the model group were not treated. The remaining three groups were respectively treated with traditional Chinese medicine, moxibustion and Western medicine. Then the changes in the rat paw swelling and pain threshold were observed. Results： The paws of rats＇ swelled significantly after injection of adjuvant. After 7 d of treatment, the rats＇ paws of CM group were still markedly swollen, and compared with the CM group, the swelling of the paws in the WM group and the moxibustion group were statistically significant （P〈0.05）. The rats＇ mechanical pain threshold of the WM group, CM group and the moxibustion group were significantly higher than that of the model group with statistical significance （all P〈0.05）. In CM group, it was higher than in the WM group with statistical significance （P〈0.05）. That in moxibustion group was higher than that in the WM group without significance between the groups （P〉0.05）. Latent period of rat＇s paw withdrawal threshold of the thermal pain in western medicine group was significantly longer than that in the model group with statistically significant （P〈0.05）. But latent period of rat＇s paw withdrawal threshold of the thermal pain in the CM group and the moxibustion group extended without statistical significance （P〉0.05）. Conclusion： The mechanical pain threshold of rats with experimental arthritis can be significantly improved by mild moxibustion and Chinese medicine treatment, which have a certain analgesic effect on rats with experimental arthritis pain.

Influence of Electroacupuncture on Tumor Necrosis Factor-αand Vascular Endothelial Growth Factor in Rats with Experimental Arthritis

Objective： To observe the effect of electroacupuncture （EA） on tumor necrosis factor-α （TNF-α） and vascular endothelial growth factor （VEGF） in peripheral blood and joint fluid of collagen-induced arthritis （CIA） rats. Methods： After CIA rat models were successfully established, the rats were given corresponding intervention treatments. The levels of TNF-α and VEGF in peripheral blood and joint fluid were measured. Results： The levels of TNF-α and VEGF levels in peripheral blood and joint fluid of CIA rats were higher than those of normal group （P〈0.05）; EA treatment significantly decreased the index levels, of significant difference compared with those before treatment （P〈0.05）, as well as the model group （P〈0.05）. Conclusion： EA can significantly decrease the TNF-α and VEGF levels in peripheral blood and joint fluid of CIA rats, and helps restrain further development of the disease.

Total glucosides of paeony improve complete freund’s adjuvant-induced rheumatoid arthritis in rats by inhibiting toll-like receptor 2-mediated tumor necrosis factor receptor-associated factor 6/nuclear factor-kappa B pathway activation

OBJECTIVE: To investigate the mechanism underlying anti-inflammatory and immunoregulatory effect of total glucosides of paeony(TGP) based on toll-like receptor 2(TLR2) mediated tumor necrosis factor(TNF) receptor-associated factor 6(TRAF6)/nuclear factor-kappa B(NF-κB) pathway activation in rats with rheumatoid arthritis.METHODS: Adjuvant arthritis(AA) model was developed by complete freund’s adjuvant(CFA) immunization. TGP(100, 50, 25 mg/kg) and celecoxib(2.8 mg/kg) were administered by intragastric administration for 21 d. Right hind paw swelling was assessed every 2 d. After 21 d, synovial changes of the ankle were detected by histopathology. CD4+and CD8+ T cell amounts in peripheral blood were measured by flow-cytometrically. Gene and protein levels of toll-like receptor(TLR)2, TRAF6, tumor necrosis factor ligand superfamily member 6(FASLG)in the spleen were assessed by RT-qPCR and Western Bolt, respectively. Nuclear expression of NF-κB p65 was detected by NF-κB p65 Assay Kit.RESULTS: Paw swelling and synovium lesions were obviously aggravated in AA rats. These symptoms were significantly relieved by TGP.The ratio of CD4+/CD8+ T cell was increased in AA rats, while TGP reduced this increased ratio.Gene and protein levels of splenic TLR2, TFAR6 and FASLG, and nuclear NF-κB p65 in AA rats were significantly increased, but overtly inhibited by TGP.CONCLUSION: These findings suggest that TGP’s anti-inflammatory effect onRA in rats with CFA may be related to the downregulation of TLR2/TRAF6/NF-κB pathway and the regulation of T cell subsets.

Effect of electroacupuncture on c-IAP1 mRNA and C-IAP2 mRNA in synovial tissues of rats with adjuvant arthritis

Objective: Td observe the therapeutic effect of electroacupuncture (EA) at Zusanli (ST 36), Guanyuan (CV 4) and Ashi points on adjuvant arthritis rats, and explore the mechanism of EA treatment of rheumatoid arthritis (RA). Methods: Sixty male rats were randomly divided into a normal group, a model group, a methotrexate group and an EA group, with 15 rats in each group. Rats in the normal group and the model group were routinely raised and did not receive treatment;rats in the methotrexate group received methotrexate at a dose of 0.35 mg/(kg bw), twice a week for 3 weeks;rats in the EA group received acupuncture at Zusanli (ST 36), Guanyuan (CV 4) and Ashi points, and the bilateral Zusanli (ST 36) and Ashi points were connected to EA apparatus, once a day for 3 weeks. The general status, the swelling degree of the toe, the arthritis index (Al) score, the pathological morphology of the ankle joint, and the mRNA expressions of cellular inhibitor of apoptosis protein (c-lAP) 1 and C-IAP2 in joint synovial tissue cells of the rats in each group were observed. Results: The swelling degree of the toe, Al score and mRNA expressions of c-IAPl and C-IAP2 in the model group were significantly higher than those in the normal group (all P<0.05). Compared with the model group, the swelling degree of the toe, Al score and mRNA expressions of c-IAPl and C-IAP2 in the methotrexate group and the EA group improved (P<0.01 or P<0.05);the expressions of c-IAPl mRNA and C-IAP2 mRNA in rat synovial tissues in the EA group were significantly higher than those in the methotrexate group (P<0.01). Conclusion: EA alleviates joint swelling in rats with adjuvant arthritis. The mechanism may be related to suppress!ng mRNA expressions of c-IAPl and C-IAP2, thus to induce apoptosis of synoviocytes.

Study on the mechanism of moxibustion for rheumatoid arthritis based on liquid chromatography-mass spectrometry

Objective To explore the mechanism of moxibustion for rheumatoid arthritis(RA)by observing the metabolite changes in urine using liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis.Methods Twenty-four rats were randomly divided into a control group,a model group,and a moxibustion group.Rats in the model and moxibustion groups were established as collagen-induced arthritis(CIA)models.The control and model groups did not receive any intervention;rats in the moxibustion group received moxibustion at Shenshu(BL23)and Zusanli(ST36).After three weeks of intervention,ankle joint,serum,and urine samples were collected for pathological examinations and metabolomic tests.Results After moxibustion treatment,the CIA rats showed increased body mass,reduced swelling of the hind paws and arthritis score,decreased serum cytokine levels,and improved histopathological evaluation of the ankle joint.Twenty-four significantly altered metabolites were found,mainly involved in alanine metabolism,taurine and hypotaurine metabolism,tricarboxylic acid cycle,phenylalanine metabolism,tyrosine metabolism,and primary bile acid biosynthesis.These metabolites may serve as potential biomarkers for RA.Conclusion Moxibustion can effectively resist inflammation in CIA rats.The potential biomarkers and the abnormal metabolic pathways of RA can be identified by LC-MS-based metabolomics.Metabolomics may be an effective way to explain the mechanism of moxibustion in treating RA.

Effects of Xinfeng capsule on pulmonary function based on treg-mediated notch pathway in a rat model of adjuvant arthritis

OBJECTIVE:To observe the impact of xinfeng xapsule(XFC) on pulmonary function in a rat model of adjuvant arthritis(AA) and to investigate the mechanism of action.METHODS:Forty rats were randomly divided into four groups of ten:normal control(NC);model control(MC);tripterygium glycosides tablet(TPT);and xinfeng capsule(XFC).Except for the NC group,AA was induced in all rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right paw on the 19th day.NC and MC groups were given(0.9%) physiological saline.The TPT and XFC groups were given TPT(10 mg/kg) and XFC(1.2 g/kg),respectively.Thirty days after administration,changes in paw edema(E),the arthritis index(AI),pulmonary function,levels of regulatory T-cells(Treg),ultrastructure of lung tissue,and expression of Notch receptors and ligands in lung tissue were observed.RESULTS:In the MC group,E and the AI were increased and pulmonary function significantly decreased;the structure of alveolar type-II cells was damaged;ratios of Treg in peripheral blood were reduced;and expression of Notch receptors such as Notch3 and Notch4 and ligands such as Delta1 in lung tissue were significantly increased whereas expression of Notch1,Jagged1 and Jagged2 were significantly decreased.After intervention with XFC,E and the AI were decreased;pulmonary function was enhanced;the structure of alveolar type-II cells was improved;and expression of Treg,Notch1,Jagged1,Jagged2 was elevated,whereas that of Notch3,Notch4 and Delta1 was reduced.CONCLUSION:XFC can not only inhibit E and the AI and improve joint symptoms,it can also improve pulmonary function and reduce inflammation in lung tissue.These actions could be carried out through increases in the expression of Treg,Notch receptors(Notch1) and ligands(Jagged1,Jagged2),and reductions in the expression of Notch3,Notch4 and Delta1.These phenomena would reduce the deposition of immune complexes and the inflammatory response in lung tissue,thereby improving joint symptoms and pulmonary function.

Mechanism studies of Xinfeng capsule on improving cardiovascular function though toll-like receptor 4/nuclear factor kappa B pathway in a rat model of adjuvant arthritis

OBJECTIVE: To observe the impact of Xinfeng capsule(XFC) on cardiovascular function in adjuvant arthritis(AA) model rats and investigate the mechanism though toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB) signaling pathway.METHODS: Seventy rats were randomly divided into seven groups: normal control(NC), model control(MC), tripterygium glycosides tablet(TPT),methotrexate(MTX), high, moderate and low dose XFC group. The administration began from day 19 after modeling for 30 day. Paw swelling, arthritic in-dex(AI), cardiac function indexes and myocardial pathological pattern were detected. The expression of TLR4, myeloid differentiation factor(My D) 88, interleukin-1 receptor-associated kinase(IRAK) 1, tumor necrosis factor receptor associated factor(TRAF) 6, NF-κB, tumor necrosis factor-alpha(TNF-α) proteins in myocardial tissue were determined by western blot method.RESULTS: Paw swelling and AI in MC group increased in MC group(P < 0.01), and decreased in high and moderate dose XFC groups(P < 0.01 or P > 0.05). Left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),heart rate(HR) were elevated in MC group(P <0.01), and ± dp/dtmax and CI were reduced(P <0.01); while LVSP, LVEDP and HR declined and ±dp/dtmax, CI improved in high dose XFC group(P <0.05 or P < 0.01). LVSP in high dose XFC group were reduced more than other treatment groups(P <0.05 or P < 0.01). The improvements on LVEDP, dp/dt-max were superior to MTX and low dose XFC group, and the improvement on CI was better than low dose XFC group(P < 0.05 or P < 0.01). Myocardial fibers arranged irregular in MC group with intracellular edema and mitochondria damage. The modifications on myocardial structural were shown in each treatment group, but more prominent in TPT, high and moderate dose XFC group. The proteins of TLR4, My D88, IRAK1, TRAF6, NF-κB, TNF-αwere highly expressed in MC group, and those proteins declined in high and moderate dose XFC group(P < 0.05 or P < 0.01). High dose XFC group was superior to MTX and low dose XFC group on reducing TLR4, NF-κB, TNF-α(P < 0.05).CONCLUSION: XFC can not only inhibit the excessive activation of TLR4/NF-κB signaling pathway and the increased inflammatory mediators, but also reduce the damage of myocardial tissue and cells.

Effects of Huatan Tongluo decoction on vascular endothelial growth factor receptor 2 expression in synovial tissues of rats with collagen-induced arthritis

OBJECTIVE: To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS: Forty specific pathogen-free Wistar rats were selected, and 10 were randomly selected as the control(group 1). The remaining rats were injected intradermally with emulsified type Ⅱ bovine collagen at the tail base and back, followed by a booster 7 d post first immunization. After establishing collagen-induced arthritis(CIA), rats were randomly divided into three groups(n = 10). The rats were treated orally for 30 d as follows: group 1, saline; group 2, model(saline); group 3, tripterygium polyglycoside(TP; 7.81 mg/kg, positive control);group 4, Huatan Tongluo decoction(HTTL; 7.5 g/kg). Body weight, ankle swelling and arthritis index were measured over the course of the study. The rats were sacrificed 30 d after treatment. Morphological changes in the synovium were observed by hematoxylin and eosin staining. Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor(VEGF) and VEGFR2 protein levels were measured by immunohistochemistry.VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction.RESULTS: Compared with the model group, a significantly lower arthritis index was observed in the positive control group(P < 0.05) and HTTL group(P < 0.01), after treatment. Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening. Furthermore, VEGF mRNA,and VEGFR2 protein and mRNA levels were significantly downregulated(P < 0.05) in the treatment groups.CONCLUSION: Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.

Effect of Xinfeng capsule on nuclear factor kappa B/tumor necrosis factor alpha and transforming growth factor beta 1/Smads pathways in rats with cardiac injuries induced by adjuvant arthritis

OBJECTIVE: To investigate effects of Xinfeng capsule(XFC) on cardiac function in rats with adjuvant arthritis(AA) and explore the mechanism of these effects.METHODS: Forty-eight rats were randomly divided into normal control(NC), model control(MC), methotrexate(MTX) and XFC groups of equal size. In all groups except for the NC group, 0.1 m L Freund's complete adjuvant(FCA) was intracutaneously injected in the right rear vola pedis to induce inflammation. Drugs were applied beginning 19 days after induction of inflammation. Normal saline was administered to the NC and MC groups and 1 mg/100 g MTX(weekly) and 0.12 g/100 g XFC(daily) to the MTX and XFC groups, respectively. Rats were sacrificed after 30 day of treatment. Toe swelling degree(TSD), arthritis index(AI), cardiac function and expression of nuclear factor kappa B(NF-κB) / tumor necrosis factor alpha(TNF-α) and transforming growth factor beta 1(TGF-β1)/Smads pathway proteins were measured.RESULTS: In the MC group, TSD and AI were greatly increased, while parameters of cardiac function were decreased and morphological analysis showed myocardial cell damage. Expression of TNF-α, NF-κB, Smad2, P-Smad2, Smad4 and TGF-β1 proteins were elevated in cardiac tissue, while Smad7 expression was decreased.TSD and AI values closely correlated to parameters of cardiac function and to levels of proteins in the NF-κB/TNF-α and TGF-β1/Smads pathways. Certain correlations were identified among TGF-β1 and NF-κB, Smad2, P-Smad2 and Smad4.With XFC intervention, both TSD and AI were decreased and parameters of cardiac function and ultrastructure of myocardial cells improved.Expressions of NF-κB, Smad2, and Smad4 proteins were greatly decreased and Smad7 expression was elevated, as compared with levels in the MC and MTX groups.CONCLUSION: XFC regulates expression of proteins in the NF-κB/TNF-α and TGF-β1/Smads pathways, decreases immune complex deposition in cardiac tissue and improves cardiac function in AA rats via upregulation of Smad7.

Effect of Xinfeng capsule on pulmonary function in a adjuvant arthritis rat model

OBjECTIVE:To observe the relationship between reduced pulmonary function and regulatory T cells(Tregs)and helper T cells(Th)1/Th2 drift in a rat model of adjuvant arthritis(AA),and to study the impact of Xinfeng capsule(XFC)on pulmonary function and investigate the mechanism of action.METHODS:Forty rats were randomly divided into normal control group(NC),model control group(MC),Tripterygium glycosides tablet group(TPT),and XFC group,with 10 in each.Except for the NCgroup,AA was induced in all rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right paw.On the 19th day after modeling,the NC and MC groups were given physiological saline(0.9%),while the TPT and XFC groups were given TPT(10 mg/kg)and XFC(2.4 g/kg),once daily,respectively.Thirty days after administration,changes in paw swelling,arthritis index(AI),pulmonary function,levels of serumγ-interferon(IFN-γ)and interleukin(IL)-4,Tregs in peripheral blood,and IFN-γ,IL-4,Forkhead box transcription factor 3(FoxP3)in lung tissue were observed by enzyme-linked immunosorbent assay,flow cytometry,polymerase chain reaction,and western blot.RESULTS:Compared with the NC group,paw swelling,AI,IFN-γ,and Th1/Th2 were increased,and pulmonary function parameters,IL-4,FoxP3 were decreased significantly in the MC group(P<0.05 or P<0.01).Pulmonary function parameters,Treg,IL-4,FoxP3(and mRNA)were higher,and paw swelling,AI,and IFN-γ(and mRNA)were lower in the XFC group than those in the MC group.The XFC group was also much better than theTPT group in improving pulmonary function,FoxP3 mRNA,IFN-γ,IL-4,Th1/Th2,and IL-10(P<0.05 or P<0.01).CONCLUSION:Xinfeng capsule can improve pulmonary function by regulating the levels of Tregs,inhibiting the activation of Th1 to Th2 cells,inducing drift,maintaining cell immune suppression,correcting the imbalance of Th1/Th2,and reducing inflammatory mediators.

Efficacy of electroacupuncture stimulating Zusanli(ST36)and Xuanzhong(GB39)on synovial angiogenesis in rats with adjuvant arthritis

OBJECTIVE:To investigate the efficacy of electroacupuncture(EA)stimulating Zusanli(ST36)and Xuanzhong(GB39)on synovial angiogenesis in rats with adjuvant arthritis(AA).METHODS:AA models were established by bilateral injection of Freund's complete adjuvant(FCA)in male Sprague-Dawley rats.Three days after injection,rats were given EA at Zusanli(ST36)and Xuanzhong(GB39)acupoints,once every other day,for 16 d.The arthritis index score,paw volume,and hematoxylin-eosin(HE)staining was performed for each animal.Angiogenesis marker cluster of differentiation 34(CD34)expression and synovial cell apoptosis in synovial tissue were observed.The levels of Notch1,hairy and enhancer of split homolog-1(Hes1),transforming growth factor-beta(TGF-β)and basic fibroblast growth factor(bFGF)were subsequently detected.RESULTS:We found that EA significantly decreased arthritis index scores,paw volume,and HE staining scores.EA could significantly inhibit the expression of CD34,promoting apoptosis of synovial cells in the joint synovial tissue of AA rats.The expression of Notch1 signaling pathway proteins and mR NAs(Notch1,Hes1,TGF-β,and bFGF)were markedly downregulated by EA treatment.CONCLUSIONS:These results prove that EA attenuates synovial angiogenesis by inhibiting the Notch1 signaling pathway in AA rat models.Based on our findings,we propose that EA is a promising complementary and alternative therapy in rheumatoid arthritis.

Electroacupuncture stimulating Zusanli(ST36),Sanyinjiao(SP6)in mice with collagen-induced arthritis leads to adenosine A2A receptor-mediated alteration of p38αmitogen-activated protein kinase signaling and inhibition of osteoclastogenesis

OBJECTIVE:To observe the effect of electroacupuncture(EA)stimulating Zusanli(ST36),Sanyinjiao(SP6)on inhibition of osteoclastogenesis and the role of the adenosine A2A receptor(A2AR)and the p38αMitogen-Activated Protein Kinase(MAPK)signaling pathway in mediating this effect.METHODS:Mice with collagen induced arthritis(CIA)received different treatments.Immunohistochemistry and western blotting were used to determine the levels of multiple signaling molecules in these joints[receptor activator of nuclear transcription factor-κB(NF-κB)ligand(RANKL),receptor activator of NF-κB(RANK),tumor necrosis factor receptor associated factor 6(TRAF6),p38α,NF-κB,and nuclear factor of activated T cells C1(NFATc1)].Osteoclasts were identified using tartrate-resistant acid phosphatase(TRAP)staining.RESULTS:The immunohistochemistry results indicated upregulation of p38α,NF-κB,and NFATc1 in the CIA-control and CIA-EA-SCH58261 groups,but reduced levels in the CIA-EA group.Western blotting indicated upregulation of RANKL,RANK,TRAF6,p38α,NF-κB,and NFATc1 in the CIA-control and CIA-EA-SCH58261 groups,but reduced expression in the CIA-EA group.Osteoclasts were more abundant in the CIA-control and CIA-EA-SCH58261 groups than in the CIA-EA group.CONCLUSIONS:EA treatment enhanced the A2AR activity and inhibited osteoclast formation by inhibition of RANKL,RANK,TRAF6,p38α,NF-κB,and NFATc1.SCH58261 reversed the effect of EA.These results suggest that EA regulated p38α-MAPK signaling by increasing A2AR activity,which inhibited osteoclastogenesis.

类风湿性关节炎实验模型的研究进展

类风湿性关节炎实验模型对于研究和发现治疗类风湿性关节炎的新药物和新疗法至关重要。归纳总结相关实验模型内容发现,胶原诱导关节炎模型在临床特征、实验室检测指标和发病机制上与类风湿性关节炎患者最为相近,被广泛应用于药物药效和作用机制的研究;病-症结合的关节炎模型能反应出中医辨证论治的特色,在中医药研究中被大量使用;成纤维样滑膜细胞模型主要应用于药物对滑膜细胞增殖和炎症反应的抑制研究,而破骨细胞模型则应用于药物对骨和软骨的保护研究。研究者需要结合自身研究方向和药物的作用特点选择合适的实验模型,以得到满意的实验结果。

应用网络药理学探究壮医清毒伸筋方治疗类风湿关节炎的作用机制

目的:网络药理学探究壮医清毒伸筋方治疗类风湿关节炎(RA)的作用机制。方法:检索中药系统药理学数据库与分析平台(TCMSP)、人类在线孟德尔遗传数据库(OMIM)、人类基因数据库(GeneCards)获取清毒伸筋方与RA交集靶点。网络可视化和分析软件(Cytoscape)获取主要活性成分,归一化相互匹配法(NCC)计算核心靶点。对核心靶点进行基因本体(GO)富集分析、京都基因与基因组百科全书(KEGG)富集分析,用分子对接分析主要活性成分与核心靶点的结合力。构建胶原诱导性关节炎(CIA)大鼠模型验证主要蛋白浓度。结果:获得145种活性成分和238个药靶点,交集靶点151个。富集分析提示交集靶点涉及19个GO富集分析条目和晚期糖基化终末产物(AGEs)-晚期糖基化终末产物受体(RAGE)信号通路、肿瘤坏死因子(TNF)信号通路等75条信号通路。主要活性成分为槲皮素、柄花黄素、豆甾醇、木犀草素、β-谷甾醇;分子对接结果显示它们与前列腺素内过氧化物合酶2(PTGS2)、基质金属蛋白酶9(MMP9)、丝氨酸/苏氨酸蛋白激酶(AKT1)等蛋白具有良好的结合性。动物实验验证,清毒伸筋方有效减轻CIA大鼠关节肿胀程度,显著降低血清MMP9、AKT1和PTGS2浓度。结论:清毒伸筋方发挥多成分、多靶点、多通路特点作用于RA的炎症级联反应。

不同脉冲波形电针对佐剂性关节炎大鼠的影响

目的 :探讨电针治疗佐剂性关节炎 (AA)最佳适宜的脉冲波形参数。方法 :将 4 0只Wistar大鼠随机分为 5组 ,电针观察组分别采用不同脉冲波形电针对AA大鼠进行治疗 ,以痛阈、关节肿胀度和炎症局部组织中 5 羟色胺 (5 HT)、β内啡肽 (β EP)、亮脑啡肽 (LEK)的含量为观察指标。结果 :治疗后不同脉冲波形电针组痛阈高于模型组 (P <0 0 5 ,P <0 0 1) ;电针组炎症局部肿胀度虽然高于正常组 (P <0 0 1) ,但较模型组为低 (P <0 0 5 ,P <0 0 1) ;电针组炎症局部组织中 5 HT含量低于模型组 (P <0 0 5 ,P <0 0 1) ;与模型组相比 ,声电波电针有升高炎症局部组织中 β EP和LEK含量的作用 (P <0 0 1,P <0 0 5 ) ,断续波电针有升高 β EP的作用 (P <0 0 5 )。结论 :电针治疗AA最佳适宜的脉冲波形为声电波。

电针对完全弗氏佐剂性小鼠外周慢性炎症痛的缓解作用

目的:探讨针刺镇痛的作用规律及其穴位作用的特异性。方法:成年雄性昆明小鼠随机分为对照组、模型组、模型加电针组和模型加假电针组,将完全弗氏佐剂(CFA)注入小鼠右后脚掌形成慢性炎症痛模型,采用辐射热缩爪潜伏期(PWL)作为痛阈指标,观察造模并给予电针治疗后PWL的变化。结果:造模后,致炎侧PWL明显缩短(P<0.05);电针双侧"足三里"和"昆仑"穴,能明显翻转缩短的PWL(P<0.05),且该效应随电针次数增加而延长,而假电针组PWL无明显变化;电针双侧"手三里"和"内关"穴不能翻转缩短的PWL(P>0.05)。结论:电针镇痛作用随针刺次数增加而增强,并在一定程度上呈穴位特异性。

针灸治疗类风湿性关节炎临床研究进展

目的:总结国内针灸防治类风湿性关节炎的研究近况,为临床科研提供参考依据和思路。方法:综合相关文献60余篇,筛选出临床常用穴并重点介绍了不同治疗方法。结果:针灸在防治类风湿性关节炎有其独特的疗效。结论:针灸治疗类风湿性关节炎前景广阔。