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.

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.

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.

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.

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.

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.

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.

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。

大黄素对膝骨关节炎大鼠软骨细胞铁死亡的影响及机制研究

目的探讨大黄素对膝骨关节炎(KOA)大鼠软骨细胞铁死亡的影响及其机制。方法96只SD大鼠分为假手术(Sham)组、KOA组、大黄素(EMO)组、大黄素+Nrf2抑制剂(EMO+ML385)组,每组24只,除Sham组外,其余组均采用改良Hulth法构建KOA模型。酶联免疫吸附试验(ELISA)检测血清肿瘤坏死因子-α(TNF-α)、一氧化氮(NO)、前列腺素E2(PGE2)水平;肉眼观察膝关节大体形态;番红O-固绿染色观察膝关节软骨组织病理形态学;原位末端标记(TUNEL)染色检测膝关节软骨细胞凋亡率;生化试剂盒检测膝关节软骨组织中丙二醛(MDA)、活性氧(ROS)、谷胱甘肽(GSH)、亚铁离子(Fe^(2+))水平;实时荧光定量PCR(qRT-PCR)、蛋白免疫印迹或免疫组化检测膝关节软骨组织中基质金属蛋白酶(MMP)-3、MMP-13、Ⅱ型胶原α1(COL2A1)、前列腺素内过氧化物合酶2(PTGS2)、谷胱甘肽过氧化物酶4(GPX4)、长链脂酰辅酶A合成酶4(ACSL4)、核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)mRNA或蛋白表达。结果与Sham组比较,KOA组大鼠血清TNF-α、NO、PGE2水平,膝关节软骨组织国际骨关节炎研究协会(OARSI)评分,细胞凋亡率,MMP-3、MMP-13、PTGS2 mRNA和蛋白表达,MDA、ROS、Fe^(2+)水平,ACSL4阳性细胞比例和ACSL4、胞核Nrf2、HO-1蛋白表达升高,GSH水平、COL2A1 mRNA和蛋白表达、GPX4阳性细胞比例和GPX4、胞质Nrf2蛋白表达降低(P<0.05),关节软骨明显破坏。EMO可改善KOA大鼠炎症反应、膝关节软骨组织损伤和软骨细胞铁死亡,同时进一步激活Nrf2/HO-1信号通路,而ML385不仅抑制Nrf2/HO-1信号通路激活,还可减弱EMO对KOA大鼠膝关节软骨组织损伤和软骨细胞铁死亡的改善作用。结论大黄素可激活Nrf2/HO-1信号通路,抑制KOA大鼠软骨细胞铁死亡,保护膝关节软骨。

基于GEO数据库对类风湿关节炎差异表达基因的分析、验证及治疗中药预测

目的:通过生物信息学方法获得类风湿关节炎(RA)的差异基因及所涉及途径,匹配预测治疗RA的潜在中药。方法:从GEO数据库下载类风湿性关节炎的基因芯片数据,确定RA样本中的差异基因、蛋白互作网络,并应用CytoHubba插件鉴定关键基因。对关键基因的GO功能和KEGG通路进行分析,阐明关键基因的生物学过程。同时采用RT-qPCR法检测CIA小鼠的脾脏差异基因表达情况对前面分析的结果进行验证。最后利用Coremine Medical数据库预测对关键基因具有显著调控作用的中药。结果:从GEO数据库获得类风湿性关节炎差异表达基因760个,GO和KEGG对其进行分析后获得CD4、CD86、TNF、CD80等核心基因20个。富集分析结果显示,白细胞活化、细胞因子介导、白细胞-细胞黏附、细胞因子活性及细胞黏附等通路对RA的发病至关重要。RT-qPCR实验结果证明,与Control组相比,CIA组小鼠脾脏的CD4、CD80、CD86表达程度升高,TNF-α表达程度降低,CD80表达变化最明显。采用COREMINE预测关键基因和通路,结果显示川牛膝、黄芪、灵芝、车前草、车前子和南星等可能针对CD4、CD86、TNF、CD80靶向治疗RA。结论:本研究明确了类风湿性关节炎的核心基因及基因所富集的通路,探讨了RA主要涉及的生物学过程,并用CIA小鼠验证了核心差异基因,为RA治疗的新靶点选择提供了支撑,预测了针对核心基因的靶向治疗中药,为治疗RA的靶向中药研究提供了依据。

中医药治疗痛风性关节炎的研究进展

痛风性关节炎是一种常见的代谢性风湿病,临床主要表现为受累关节的红肿热痛及功能障碍。现阶段中医药治疗痛风的手段众多,疗效确切且不良反应较西药少。临床中常用中药内服、中药外敷、针刺等疗法治疗痛风性关节炎,诸法联合运用疗效更好。实验研究表明,中医药治疗痛风的机制与调节嘌呤代谢、降低血尿酸、下调炎症因子水平、调控细胞凋亡及线粒体自噬、提高抗氧化应激、调节肠道菌群等密切相关。这些研究结果对深入挖掘中医药治疗痛风性关节炎的有效活性成分与分子机制具有非常重要的意义。本文从实验研究与临床应用对中医药治疗痛风性关节炎进行综述,以期进一步阐明中医药治疗痛风的作用机制,为临床诊疗应用提供新思路。

基于NF-κB信号通路探讨牛膝总皂苷治疗膝骨性关节炎滑膜炎症效果机制

目的基于NF-κB信号通路探讨牛膝总皂苷治疗膝骨性关节炎滑膜炎症的机制。方法选择SPF级SD大鼠60只,随机分成对比组、模型组、牛膝总皂苷低剂量组、牛膝总皂苷中剂量组、牛膝总皂苷高剂量组,每组12只。除对比组外,其他各组大鼠在关节两侧进针,从第1天开始每间隔2 d分别注射0.3 mL 5%木瓜蛋白酶水溶液到大鼠膝关节腔内,比较5组大鼠关节炎症指标。结果与对比组比较,模型组的膝关节肿胀程度较严重,miR-19α的基因表达水平较低,而SOX9、NF-κB的基因水平表达较高,使用牛膝总皂苷的3组,根据剂量的增加肿胀水平依次降低,miR-19α基因表达水平依次增高,而SOX9以及NF-κB的基因表达水平和蛋白表达水平依次降低。结论牛膝总皂苷能减轻骨关节炎的炎症症状,并且能通过上调miR-19α的表达抑制SOX9、NF-κB的表达水平,保护软骨细胞的凋亡。

非能动安全壳热量导出系统换热器部分失效对安全壳内热工参数的影响

为探究非能动安全壳热量导出系统换热器部分失效对安全壳内热工参数的影响,本文利用PANGU试验装置研究了在发生LBLOCA事故且部分非能动安全壳热量导出系统换热器失效的工况下,换热器部分失效对非能动安全壳热量导出系统的工作状态的影响以及壳内温度分布的影响。结果表明:发生LBLOCA事故时,在部分非能动安全壳热量导出系统被隔离的情况下,剩余的非能动安全壳热量导出系统排热功率显著增加,壳内峰值压力和长期稳定压力分别上升了约8.3%和13%,仍远低于壳内压力限值。在事故进程中,温度分布不均匀性主要出现在前期以及中期阶段,后其温度分布逐渐趋于均匀。

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。