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.

ClinicalandExperimentalStudyofRAMixtureinTreatmentofRhematoidArthritislxl

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.

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.

Use of Xinfeng capsule to treat abarticular pathologic changes in patients with rheumatoid arthritis

OBJECTIVE: To observe the influence of Xinfengcapsule(XFC) on abarticular pathologic changes(APCs) and other indices of patients with rheumatoid arthritis(RA) and explore the mechanism of action of XFC in improving such changes.METHODS: Three-hundred RA patients were divided randomly into a treatment group(n=150) and control group(n=150). A normal control(NC)group(n=90) was also created. Changes in cardiac function, pulmonary function, anemia indices and platelet parameters of RA patients were measured.Curative effects of the two groups were compared,and comparison carried out with the NC group.RESULTS: In 300 RA patients, late diastolic peak flow velocity(A peak) was much higher(P<0.01)and early diastolic peak flow velocity(E peak), E/A,and left ventricular fraction shortening much lower(P<0.01) than those in the NC group. Vital capacity(VC), forced vital capacity in one second, forced vital capacity(FVC), maximal voluntary ventilation(MVV), maximal expiratory flow in 50% of VC(FEF50) and FEF75 were lowered remarkably(P<0.05 or P<0.01). Platelet count(PLT), plateletcrit(PCT) and mean platelet volume(MPV) increased markedly(P<0.05 or P<0.01), and hemoglobin(Hb)level decreased significantly(P<0.05). After XFC treatment, the A peak and PLT and PCT were much lower(P<0.05), and E/A and the number of red blood cells as well as Hb level were much higher(P<0.05), as were FVC, MVV and FEF50(P<0.05 or P<0.01), in the treatment group than those in the NC group. Total score of pain and swelling in joints,uric-acid level and high-sensitivity C-reactive protein level were much lower, and superoxide dismutase level as well as the number of CD4 +CD25+ regulation T cells(Treg) and CD4+CD25+CD127- Treg were much higher(P<0.05 or P<0.01)in the treatment group than those in the NC group.CONCLUSION: RA patients with pathologic changes in joints also suffer from lower cardiac and pulmonary functions and from parameters of anemia and platelet factors. XFC can improve the symptoms of RA patients, ameliorate their cardiac and pulmonary functions and reduce the parameters of anemia and platelet factors. XFC lowers the immune inflammatory reaction to improve APCs in RA patients.

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.

Utility of arthroscopic guided synovial biopsy in understanding synovial tissue pathology in health and disease states

The synovium is the soft tissue lining diarthrodial joints, tendon sheaths and bursae and is composed of intimal and subintimal layers. The intimal layer is composed of type A cells(macrophages) and type B cells(fibroblasts); in health, the subintima has few inflammatory cells. The synovium performs several homeostatic functions and is the primary target in several inflammatory arthritides. Inflammatory states are characterised by thickening of the synovial lining, macrophage recruitment and fibroblast proliferation, and an influx of inflammatory cells including lymphocytes, monocytes and plasma cells. Of the various methods employed to perform synovial biopsies arthroscopic techniques are considered the "gold standard", and have an established safety record. Synovial biopsy has been of critical importance in understanding disease pathogenesis and has provided insight into mechanisms of action of targeted therapies by way of direct evidence about eventsin the synovial tissue in various arthritides. It has been very useful as a research tool for proof of concept studies to assess efficacy and mechanisms of new therapies, provide tissue for in vitro studies, proteomics and microarrays and allow evaluation for biomarkers that may help predict response to therapy and identify new targets for drug development. It also has diagnostic value in the evaluation of neoplastic or granulomatous disease or infection when synovial fluid analysis is noncontributory.

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.

Zuogui pills for myelinolysis in a rat model of experimental autoimmune encephalomyelitis

Zuogui pills have been shown to attenuate the inflammatory reaction in a rat model of experimental autoimmune encephalomyelitis （EAE）. The present study attempted to investigate the pathology underlying the influence of Zuogui pills on myelinolysis in EAE rats. Hematoxylin-eosin and Luxol fast blue staining showed that the myelinolysis foci in the cerebrum, cerebellum, brain stem, and the spinal cord of EAE rats were significantly decreased, along with serum myelin basic protein content following treatment with Zuogui pills.

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.

Thrombospondin-1 expression correlates with angiogenesis in experimental cirrhosis

AIM:To investigate the significance of Thrombospondin-1 (TSP-1) expression and its relationship with angiogenesis during experimental fibrosis. METHODS:Cirrhosis was induced in male Wistar rats by intraperitoneal administration of diethyl nitrosamine (DEN). The serial sections from liver tissues were stained with anti-CD34 and anti-TSP-1 antibodies before being quantitated by light microscopy. RESULTS:Our results showed that of TSP-1 expression gradually increases according to the severity of fibrosis (GroupⅠvs group Ⅱ, Group Ⅲ and Group Ⅳ;Group Ⅱ vs group Ⅲ and group Ⅳ;group Ⅲ vs group Ⅳ, P < 0.05). Moreover, TSP-1 expression was found to be correlated with angiogenesis (P < 0.05). CONCLUSION:The correlative evidence of the link between TSP-1 and fibrosis or angiogenesis provided by this study suggests that besides its role as a strong promoter of transforming growth factor-β1 (TGF-β1), TSP-1 might have an additional role in liver fibrogenesis by stimulating angiogenesis and this protein could be a potential target to prevent fibrogenesis in chronic inflammatory diseases of the liver.

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.

An Experimental Study on the Treatment with High Dose Dexamethasone of Craniocerebral Injury Caused by 7.62mm Bullets in Dogs

The effect of high dose dexamethasone(5 mg/kg wt,intravenous injection)to preventand treat secondary pathological damage due to craniocerebral injury was studied in an animal modelof craniocerebral injury caused by high-velocity missiles in dogs.We observed the physiologicalchanges,analyzed the level of serum and cerebrospinal fluid lactate dehydrogenase,cstimated thepermeability of blood brain barrier(BBB)and studied brain pathology by light and electronmicroscopy.The rusults suggest that high dose dexarnethasone can help to restore the structure andfunction of BBB,protect the brain cells,lessen the secondary pathological damage in the respiratoryand circulatory systams,and reduce the production of lipoperoxides(LPO).

Ultrastructural Pathology of Nerve Cells in Mouse Brain Infected with Epidemic B Encephalitis Virus

An animal model of epidemic(Japanese)B encephalitis was estabilisged by injecting theJin Wei Yah 1 stain of B encephalitis virus into the peritoneal cavity of mice.The ultrastructuralchanges of the nerve cells in their brains were studied,special attention being paid to some types ofnerve cell in the cerebellar cortex.The infectet Purkinje cells and especially the granular cells showedspecial and inter,sting pathological features.These were compared with the changes found in the in-fected nerve cells in the cerebral cortex,diencephalon and mesencephalon.A radiating structure consisting of a microveside-microtubule aggregation body at the centerand endoplastic reticulum or virus replication multivesicular structures around it was often found in thein fected nerve cells.Its morphological features were described in detail,and its significance and the se-quenoe of events of its development discussed.In the late stage of infection,virus particles were found in the nuclei of part of the necroticcells.It is considered that they entered the nuclei from the cytoplasm during or after the death of theinfected cells.The observation smade in this study have comfimed in the granular cell of the cerebellum theidea of Chert et al.that the encephalitis B virus particle can he formed in the perinudear cistem ofthe infected nerve cell,and have brought forth further information in this respect.The way of releaseof the virus particles from the infected nerve cells observed in this study is fundamentally consistentwith that observed by Chen et al.but most of the virus particles left the nerve cell via the cell pro-

肌骨超声在类风湿关节炎和痛风性关节炎患者有症状关节病变诊断中的作用比较

目的应用肌骨超声(MSUS)比较类风湿关节炎(RA)和痛风性关节炎(GA)有症状关节病变的超声征象。方法回顾性分析85例RA住院患者和同期55例GA住院患者,比较两组一般资料、病变关节情况及超声征象的差异。结果两组性别、年龄段、病变关节情况比较差异均有统计学意义(均P<0.05);膝关节病变检出率均最高;RA组滑膜炎灵敏度高、半月板损伤特异度高、骨侵蚀诊断效能高,GA组点状强回声、双轨征、痛风石3项联合超声征象诊断效能高于任一项单独诊断且灵敏度和特异度也较高;RA组病程与骨侵蚀呈正相关(P<0.05),GA组病程与痛风石呈正相关(P<0.05)。结论RA与GA的超声征象具有一定差异,MSUS在二者诊断及鉴别诊断上具有较好价值。

不同制备工艺的坤痹消方治疗类风湿关节炎的药效学研究

目的:筛选坤痹消方治疗类风湿关节炎(RA)的最佳制备工艺。方法:根据制备方法的不同,将坤痹消方分为3种制备工艺。建立雄性及雌性牛Ⅱ型胶原诱导关节炎(CIA)大鼠模型,通过足肿胀体积、关节炎指数、脾脏指数、膝关节病理评估不同工艺的坤痹消方对RA的治疗作用。建立雄性及雌性小鼠醋酸扭体疼痛模型,通过扭体次数评估不同工艺的坤痹消方的镇痛作用。结果:坤痹消方工艺2能够显著降低雄性及雌性CIA大鼠足肿胀体积、关节炎指数(P<0.01;P<0.05);坤痹消方工艺2、工艺3均能降低雌性CIA大鼠脾脏指数(P<0.01;P<0.05);在病理损伤方面,坤痹消方工艺2能够显著改善雄性及雌性CIA大鼠滑膜增生及炎症细胞浸润程度(P<0.05;P<0.01)。在镇痛方面,坤痹消方工艺2能显著降低雄性小鼠扭体次数(P<0.01);坤痹消方工艺3能显著降低雄性及雌性小鼠扭体次数(P<0.05)。结论:坤痹消方工艺2能够改善CIA大鼠关节炎症,减轻膝关节的病理损伤,并有一定的镇痛作用,为坤痹消方的最优工艺。