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1.
Article in Chinese | WPRIM | ID: wpr-921711

ABSTRACT

Sophorae Flavescentis Radix, the root of Sophora flavescens Ait., has been widely applied in the medical field due to its anti-inflammatory, analgesic, bacteriostatic, antiviral, antitumor, and other pharmacological effects. The present study investigated the anti-rheumatoid arthritis effect of oxymatrine(OMT), the active component of Sophorae Flavescentis Radix by observing its effect on the function of B lymphocytes in collagen-induced arthritis(CIA) mice through the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/signal transducer and activator of transcription 3(STAT3) pathway. The CIA model in DBA/1 J mice was induced by bovine type Ⅱ collagen and complete Freund's adjuvant(CFA). Fifteen days after the primary immunization, mice were treated with OMT for 30 days by intraperitoneal injection. Paw swelling and arthritis index(AI) score were evaluated every 3 days. Joint histopathologic changes were observed by HE staining. Magnetic-activated cell sorting(MACS) was used to isolate B lymphocytes from the spleen of CIA mice spleen. The serum expression level of interleukin(IL)-21 was examined by the enzyme-linked immunosorbent assay(ELISA). The expression of TLR9, STAT3, p-STAT3, and IL-21 in B lymphocytes was detected by Western blot. The mRNA expression of TLR9, STAT3, and IL-21 in B lymphocytes was detected by real-time fluorescence-based quantitative PCR(qRT-PCR). The results showed that OMT could significantly alleviate the paw swelling, decrease the AI score, relieve synovial inflammatory cell infiltration and hyperplasia, reduce the level of inflammatory cytokines, and inhibit the expression of TLR9, STAT3, p-STAT3, and IL-21 of B lymphocytes in CIA mice. Therefore, OMT may alleviate rheumatoid arthritis by regulating TLR9/MyD88/STAT3 pathway in B lymphocytes, providing a valuable reference for the application of OMT in the clinical treatment of rheumatoid arthritis.


Subject(s)
Alkaloids , Animals , Arthritis, Experimental/genetics , Cattle , Cytokines , Mice , Mice, Inbred DBA , Quinolizines
2.
Chinese Acupuncture & Moxibustion ; (12): 1119-1125, 2021.
Article in Chinese | WPRIM | ID: wpr-921020

ABSTRACT

OBJECTIVE@#To observe the effect of moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) on inflammatory factors and intestinal flora in the rats with adjuvant arthritis.@*METHODS@#A total of 36 Wistar rats were randomized into a normal group, a model group and a moxibustion group, 12 rats in each one. In the model group and the moxibustion group, the adjuvant arthritis model was established by a compound method, including the environmental factors, i.e. wind, cold and damp, and Freund's complete adjuvant. In the moxibustion group, moxibustion intervention was exerted at "Zusanli" (ST 36) and "Shenshu" (BL 23), for 20 min at each acupoint, once daily, consecutively for 21 days. The paw swelling degree and arthritis index (AI) score were observed before and after intervention in the rats of each group. Using real-time fluorescence quantitative PCR method (real-time PCR) and Western blot method, the mRNA and protein expressions of inflammatory factors of colon tissue, i.e. interleukin (IL) 1β, tumor necrosis factor-α (TNF-α), IL-6, were detected after intervention in the rats of each group. The intestinal flora was detected with 16SrRNA sequencing technology after intervention in the rats of each group.@*RESULTS@#Compared with the normal group, the paw swelling degree and AI score were increased in the rats of the model group (@*CONCLUSION@#Moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) relieves the joint symptoms of adjuvant arthritis rats and inhibits the expressions of inflammatory factors, which is probably related to the regulation of the structure of intestinal flora.


Subject(s)
Animals , Arthritis, Experimental/therapy , Arthritis, Rheumatoid , Gastrointestinal Microbiome , Moxibustion , Rats , Rats, Wistar
3.
Article in Chinese | WPRIM | ID: wpr-888152

ABSTRACT

In this study, we investigated the mechanism of crude extract of Psammosilene tunicoides(CEPT) in the treatment of rheumatoid arthritis(RA) based on the Nod-like receptor protein 3(NLRP3) inflammasome. The collagen-induced arthritis(CIA) mouse model was established. On day 32 after the primary immunization, according to the arthritis score, the mice were randomly divided into model group, positive control(methotrexate) group, low-and high-dose CEPT groups, and normal group, with 10 mice in each group. According to the administration dose of each group, the mice were continuously administered for 21 days. Every four days during the administration, the paw edema degree, arthritis score, and spleen index of the mice were measured; histopathological examination was performed for the ankles of the mice; the contents of IL-1β and IL-18 in the serum were determined; the protein expression levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a CARD(ASC), as well as the mRNA expression levels of NLRP3 and caspase-1 in the ankle joints of the mice were detected. The results showed that compared with those in the model group, the mice in the positive control group and CEPT groups had significantly decreased the contents of IL-1β and IL-18 in the serum and spleen index(P<0.01), significantly lowered arthritis score and degree of paw edema(P<0.01), alleviated arthritic infiltration of the knee, and down-regulated protein and mRNA levels of NLRP3, ASC, and caspase-1 in the ankle joint(P<0.01). These results suggest that P. tunicoides may reduce the paw edema and arthritis score and alleviate the inflammatory response in CIA mice by inhibiting the expression of NLRP3. This study provides a basis for the study of immune regulation of P. tunicoides in RA.


Subject(s)
Animals , Arthritis, Experimental/genetics , Arthritis, Rheumatoid/genetics , Caspase 1/genetics , Inflammasomes/genetics , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/genetics
4.
Afro-Egypt. j. infect. enem. Dis ; 1(3): 199-208, 2020. ilus
Article in English | AIM, AIM | ID: biblio-1258725

ABSTRACT

Background: The aim of Trichinella inspection is to reliably detect larvae in meat at levels which are capable of causing human trichinellosis. Trichinoscopy is a rapid, cost effective but is less sensitive in detection of low muscle larvae (ML)numbers. Artificial digestion is more convenient, and flexible, but may destroy immature larvae. Baermann technique may enhance the efficiency of diagnosis. Giemsa and Leishman stains provide identical contrasting coloration as Hematoxylin and Eosin (H-E) with the both advantages of that they can be used for staining non-histological sectionsand rapid preparation.The primary aim of the study was to compare the efficiency of digestion and Baermann techniques for detection of ML in muscles. Secondary aim was detection of ML by Geimsa and Leishman stain and their comparison with routinely used stain H-E. Methods: Muscles from 36 mice orally infected with Trichinella spiralis encysted larvae were examined. Larvae from 1 g samples of different muscles were recovered by digestion and Baermann techniques after different dose of infection. Muscle samples were prepared for staining with Giemsa, Leishman and H-E. Results: Number of larvae recovered by Baermann was higher recovered by digestion method (P ˃0.5). Leishman stain was the best stain for rapid detection of ML after 30 min followed in validity by Geimsa then H-E. Conclusion: Baermann concentration technique showed higher sensitivity than digestion method. Leishman stain is superior to Giemsa stain as it takes less time. Both stains are considered good alternative to H-E for rapid and easy diagnosis of trichinellosis in post-mortem animals


Subject(s)
Arthritis, Experimental , Azure Stains , Digestion , Egypt
5.
Braz. j. med. biol. res ; 53(6): e9489, 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132521

ABSTRACT

Rheumatoid arthritis (RA) is an autoimmune disease of knee joints involving pain and inflammation. Rhoifolin is a plant flavonoid known to have antioxidant and anti-inflammatory properties. This study was taken to identify the effect of rhoifolin on complete Freund's adjuvant (CFA)-induced arthritis in the rat model. Treatment with rhoifolin (10 and 20 mg/kg) showed a significant improvement in the overall health parameters such as paw edema and weight loss. This improvement in morphological parameters corroborated the findings with gross morphological changes observed in the histopathological analysis. Rhoifolin treatment also caused a significant decrease in oxidative stress, evident from changes in intracellular levels of glutathione, glutathione peroxidase, malondialdehyde, and superoxide dismutase in the articular cartilage tissue. Moreover, proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin(IL)-1β, and IL-6 showed a significant downregulation of gene expression and intracellular protein concentration levels. The NF-κB pathway showed a significant attenuation as evident in the significant reduction in the levels of NF-κB p65 and p-IκB-α. These results indicated that rhoifolin can be a natural therapeutic alternative to the extant regimens, which include non-steroidal anti-inflammatory drugs and immunosuppressants. Additionally, the antioxidant and anti-inflammatory action of rhoifolin was probably mediated by the NF-κB pathway. However, the exact target molecules of this pathway need to be determined in further studies.


Subject(s)
Animals , Male , Rats , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Flavonoids/administration & dosage , Freund's Adjuvant/administration & dosage , Cytokines/blood , Oxidative Stress/drug effects , Disaccharides/administration & dosage , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/metabolism , Biomarkers/blood , NF-kappa B/drug effects , NF-kappa B/metabolism , Interleukin-6/blood , Tumor Necrosis Factor-alpha/blood , Interleukin-1beta/blood , Glycosides/administration & dosage
6.
Article in Chinese | WPRIM | ID: wpr-828905

ABSTRACT

OBJECTIVE@#To investigate the expression of citrullinated epitopes in articular cartilage protein and whether its expression is sufficient to induce anti-citrullinated protein antibody (ACPA) response in mice.@*METHODS@#The experimental group was treated with different concentrations of lipopolysaccharide (LPS), heat-inactivated bacteria ( and ) or specific monoclonal antibody against type Ⅱ collagen to induce citrullination of articular cartilage protein, with PBS as the control. Immunohistochemistry with the monoclonal antibody ACC4 (IgG1) that specifically binds to the citrullinated epitope of cartilage protein was performed for detecting the expression of citrullinated protein, with ACC1 (IgG2a) as a positive control antibody and L243 (IgG2a) and Hy2.15 (IgG1) as the negative isotype control. In the in vivo experiment, SD rats were subjected to injection of different doses of LPS in the right knee (with PBS as the controls in the left knee), and 3 days later frozen sections were prepared for immunohistochemical detection of the expression of citrullinated protein. Models of collagen-induced arthritis (CIA) established in different mouse strains were observed for incidence and severity of CIA. Serum samples collected from these models and the sera from rheumatoid arthritis patients were examined for anti-citrullinated protein antibody, and immunohistochemistry was performed to detect the expression of citrullinated protein in the cartilage of the mouse.@*RESULTS@#The citrullinated CII epitope-specific antibody ACC4 did not bind to articular cartilage tissues with different treatments as compared with the positive control antibody ACC1. The ACC4 antibody and the antibodies from patients with rheumatoid arthritis with high titers of anti-citrullinated protein antibody were capable of binding to the synovial tissue around the articular cartilage of the CIA. Luminex analysis showed that the anti-citrullinated protein antibody was lowly expressed in mouse serum, but the anti-type Ⅱ collagen triple helix structure peptide antibody exhibited strong reactivity.@*CONCLUSIONS@#Mild acute inflammatory response is not enough to cause citrullination of articular cartilage protein, and the expression of specific epitope requires a high-intensity inflammatory response. Inflammatory articular cartilage protein can express citrullinated epitopes in type Ⅱ collagen-induced arthritis in mice, but the expression of citrullinated epitopes is not sufficient to induce an immune response to anti-citrullinated antibodies. Stronger stimulation signals are required to induce an immune response for producing anti-citrullinated protein antibodies.


Subject(s)
Animals , Arthritis, Experimental , Autoantibodies , Cartilage, Articular , Citrulline , Humans , Inflammation , Mice , Rats , Rats, Sprague-Dawley
7.
Article in Chinese | WPRIM | ID: wpr-880777

ABSTRACT

OBJECTIVE@#To explore the mechanism of @*METHODS@#Healthy male DBA/1 mice were used for CIA modeling. Twenty-five CIA mice with successful modeling and similar arthritis index (AI) scores were randomized equally into model group (CIA), methotrexate (MTX) group, and low-, medium-, and high-dose XWGD groups (0.975, 1.95, and 3.9 g/mL, respectively), with another 5 normal mice as the normal control group. The mice in normal control and CIA groups were given saline once a day, those in MTX group were given 0.1 mg/mL MTX once a week, and those in XWGD groups were treated daily via garage of XWGD containing crude drugs of different doses for 28 consecutive days. The AI score and HE staining were used to evaluate the changes in the joints of the CIA mice. The effect of XWGD on Th1, Th17, MDSC, G-MDSC and M-MDSC cells were evaluated with flow cytometry.@*RESULTS@#Treatment with MTX and different doses of XWGD significantly decreased the AI score of the mice and relieved joint inflammation as compared with the model group (@*CONCLUSIONS@#XWGD can improve joint inflammation in CIA mice by increasing the percentages of G-MDSC cells and decreasing the percentages of M-MDSC, Th1 and Th17 cells, and a high dose of XWGD can produce an equivalent therapeutic effect to methotrexate but with better safety.


Subject(s)
Animals , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Male , Methotrexate , Mice , Mice, Inbred DBA , Th17 Cells
8.
Braz. j. med. biol. res ; 53(3): e8969, 2020. tab, graf
Article in English | LILACS | ID: biblio-1089337

ABSTRACT

This study investigated the repercussions of adjuvant-induced arthritis (AIA) on body composition and the structural organization of the soleus and cardiac muscles, including their vascularization, at different times of disease manifestation. Male rats were submitted to AIA induction by intradermal administration of 100 μL of Mycobacterium tuberculosis (50 mg/mL), in the right hind paw. Animals submitted to AIA were studied 4 (AIA4), 15 (AIA15), and 40 (AIA40) days after AIA induction as well as a control group of animals not submitted to AIA. Unlike the control animals, AIA animals did not gain body mass throughout the evolution of the disease. AIA reduced food consumption, but only on the 40th day after induction. In the soleus muscle, AIA reduced the wet mass in a time-dependent manner but increased the capillary density by the 15th day and the fiber density by both 15 and 40 days after induction. The diameter of the soleus fiber decreased from the 4th day after AIA induction as well as the capillary/fiber ratio, which was most evident on the 40th day. Moreover, AIA induced slight histopathological changes in the cardiac muscle that were more evident on the 15th day after induction. In conclusion, AIA-induced changes in body composition as well as in the soleus muscle fibers and vasculature have early onset but are more evident by the 15th day after induction. Moreover, the heart may be a target organ of AIA, although less sensitive than skeletal muscles.


Subject(s)
Animals , Male , Rats , Arthritis, Experimental/pathology , Body Composition , Muscle, Skeletal/pathology , Myocardium/pathology , Arthritis, Experimental/metabolism , Muscle, Skeletal/metabolism , Disease Models, Animal , Myocardium/metabolism
9.
Sci. med. (Porto Alegre, Online) ; 29(2): ID32705, 2019.
Article in Portuguese | LILACS | ID: biblio-1022316

ABSTRACT

OBJETIVOS: Avaliar a eficácia da terapia fotodinâmica com Brilliant Blue G no tratamento de um modelo experimental de artrite por Paracoccidioides brasiliensis (P. brasiliensis). MÉTODOS: Após a indução de artrite experimental com isolado de P. brasiliensis da linhagem Pb18 nos joelhos de ratos Wistar, os animais foram divididos em grupos e submetidos a terapia fotodinâmica com fotossensibilizador Brilliant Blue G intra-articular e a laserterapia apenas, sem o Brilliant Blue G. Todos os grupos receberam seus respectivos tratamentos do sétimo ao 11º dia. Para análise do edema foi mensurado o diâmetro latero-lateral do joelho de cada animal diariamente e após o período de tratamento os animais foram sacrificados para dissecação do joelho experimental e coleta de sangue para análise por ELISA, a fim de quantificar os níveis de anticorpos anti-P. brasiliensis. RESULTADOS: A aplicação da terapia fotodinâmica foi capaz de impedir a formação de edema quando comparado ao controle (p>0,005), bem como a produção de anticorpos anti-Gp-43 de P. brasiliensis (p=0,001). No exame anatomopatológico foi possível observar maior grau de sinovite e maior presença de granulomas com o fungo em seu interior no grupo que não recebeu tratamento quando comparado aos grupos que receberam a terapia fotodinâmica. CONCLUSÕES: A terapia fotodinâmica foi eficaz para atenuar a artrite experimental induzida por P. brasiliensis no modelo articular proposto.


AIMS: To evaluate the effectiveness of photodynamic therapy with Brilliant Blue G in the treatment of an experimental model of arthritis by Paracoccidioides brasiliensis (P. brasiliensis). METHODS: After the induction of experimental arthritis with isolated from P. brasiliensis of lineage Pb18 in the knees of Wistar rats, the animals were divided into groups and submitted to photodynamic therapy with intra-articular Brilliant Blue G photosensitizer and laser therapy only, without Brilliant Blue G. All groups received their respective treatments from the seventh to the 11th day. For edema analysis, the knee lateral-lateral diameter of each animal was measured daily and after the treatment period the animals were sacrificed for experimental knee dissection and blood collection for analysis by ELISA, in order to quantify levels of anti-P. brasiliensis antibodies. RESULTS: The results showed that the application of photodynamic therapy was able to prevent the formation of edema when compared to the control (p>0.005), as well as the production of anti-Gp-43 antibodies from P. brasiliensis (p=0.001). In the anatomopathological examination it was possible to observe a higher degree of synovitis and a greater presence of granulomas with the fungus inside the group that did not receive treatment when compared to the groups that received the photodynamic therapy. CONCLUSIONS: Photodynamic therapy was effective in attenuating the experimental arthritis induced by P. brasiliensis in the proposed joint model.


Subject(s)
Photochemotherapy , Paracoccidioides , Arthritis, Experimental , Rheumatology , Medicine
10.
Biol. Res ; 52: 45, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019509

ABSTRACT

BACKGROUND: Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes In adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. RESULTS: In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. CONCLUSION: These results indicated that resveratrol reduced store-operated Ca2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis.


Subject(s)
Animals , Rats , Arthritis, Experimental/physiopathology , Calcium Channels/drug effects , Apoptosis/drug effects , Fibroblasts/drug effects , Synoviocytes/drug effects , Stromal Interaction Molecule 1/drug effects , ORAI1 Protein/drug effects , Resveratrol/pharmacology , Calcium Channels/physiology , Oxidative Stress/drug effects , Resveratrol/administration & dosage , Mitochondria/drug effects
11.
Article in English | WPRIM | ID: wpr-719461

ABSTRACT

OBJECTIVE: We undertook this study to investigate the discriminant metabolites in urine from patients with established rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and from healthy individuals. METHODS: Urine samples were collected from 148 RA patients, 41 SLE patients and 104 healthy participants. The urinary metabolomic profiles were assessed using 1H nuclear magnetic resonance spectroscopy. The relationships between discriminant metabolites and clinical variables were assessed. Collagen-induced arthritis was induced in mice to determine if a choline-rich diet reduces arthritis progression. RESULTS: The urinary metabolic fingerprint of patients with established RA differs from that of healthy controls and SLE patients. Markers of altered gut microbiota (trimethylamine-N-oxide, TMAO), and oxidative stress (dimethylamine) were upregulated in patients with RA. In contrast, markers of mitochondrial dysfunction (citrate and succinate) and metabolic waste products (p-cresol sulfate, p-CS) were downregulated in patients with RA. TMAO and dimethylamine were negatively associated with serum inflammatory markers in RA patients. In particular, patients with lower p-CS levels exhibited a more rapid radiographic progression over two years than did those with higher p-CS levels. The in vivo functional study demonstrated that mice fed with 1% choline, a source of TMAO experienced a less severe form of collagen-induced arthritis than did those fed a control diet. CONCLUSION: Patients with RA showed a distinct urinary metabolomics pattern. Urinary metabolites can reflect a pattern indicative of inflammation and accelerated radiographic progression of RA. A choline-rich diet reduces experimentally-induced arthritis. This finding suggests that the interaction between diet and the intestinal microbiota contributes to the RA phenotype.


Subject(s)
Animals , Arthritis , Arthritis, Experimental , Arthritis, Rheumatoid , Choline , Dermatoglyphics , Diet , Gastrointestinal Microbiome , Healthy Volunteers , Humans , Inflammation , Lupus Erythematosus, Systemic , Magnetic Resonance Spectroscopy , Metabolome , Metabolomics , Mice , Oxidative Stress , Phenotype , Spectrum Analysis , Waste Products
12.
Yonsei Medical Journal ; : 88-97, 2019.
Article in English | WPRIM | ID: wpr-719377

ABSTRACT

PURPOSE: Sodium chloride (NaCl) has been proposed as a driving factor in autoimmune diseases through the induction of pathogenic CD4+ T helper cells that produce interleukin-17 (Th17 cells). This study investigated the effects of NaCl on inflammatory arthritis in mice and humans. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) mice were fed a normal or high-salt diet ad libitum, and clinical and histologic features of arthritis were evaluated. The proportion of Th17 cells in the spleens of CIA mice fed a normal or high-salt diet was evaluated by flow cytometry, and the expression of IL-17 in joints and intestines was determined by immunohistochemical staining. We also analyzed the effect of NaCl on Th17 differentiation from peripheral blood monocytes of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and evaluated the contents of sodium and IL-17 in the synovial fluid of RA and OA patients. RESULTS: NaCl increased murine and human Th17 cell differentiation in a dose-dependent manner. Clinical and histological arthritis was more severe in the high-salt-fed CIA mice, compared to control CIA mice. The proportion of Th17 cells among splenocytes was higher in CIA mice fed a high-salt diet. Expression of synovial and intestinal IL-17 was also higher in high-salt-fed CIA mice. Comparison of synovial fluid between RA patients and OA patients revealed that Na+ and IL-17 were more abundant in RA synovial fluid. CONCLUSION: This study suggests that NaCl can aggravate arthritis by affecting Th17 differentiation. Accordingly, limiting salt intake may be helpful for treating inflammatory arthritis, such as RA.


Subject(s)
Animals , Arthritis , Arthritis, Experimental , Arthritis, Rheumatoid , Autoimmune Diseases , Diet , Flow Cytometry , Humans , Interleukin-17 , Intestines , Joints , Mice , Monocytes , Osteoarthritis , Sodium Chloride , Sodium , Spleen , Synovial Fluid , T-Lymphocytes, Helper-Inducer , Th17 Cells
13.
Article in Chinese | WPRIM | ID: wpr-774595

ABSTRACT

To investigate the " drug-guide" effect of Achyranthes bidentata saponins( ABS) and geniposide( GE) in the treatment on adjuvant arthritis( AA) rats. A UHPLC-MS/MS method for the quantitative determination of GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa in rat blood and joint dialysate was established. After single or combined administration with ABS and GE was given to AA rat model,a microdialysis sampling method for rat joint cavity and jugular vein blood vessels was established to collect microdialysis samples. Waters Acquity HSS C_(18) column was used to separate the above four components,with mobile phase as acetonitrile-0. 1% formic acid water as mobile phase for gradient elution. ESI source was adopted for mass spectra in a negative ion scanning mode. Multiple reaction monitoring( MRM) mode was applied to detect the above four components. The methodological results showed that GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa demonstrated a good linear relationship within the concentration ranges of 2-4 000,16-4 096,14-3 584,23-5 888 μg·L-1 respectively. The precision,accuracy,stability and matrix effect of these four ingredients reached the requirements of quantitative analysis of biological samples. The pharmacokinetic results demonstrated that the combined administration of ABS and GE( 60 mg·kg~(-1)+60 mg·kg~(-1)) can increase the degree of GE in joint cavity distribution,and the AUCjoint/AUCplasmwere twice of that of single administration of GE( 60 mg·kg~(-1)),which indicated that ABS might played a vital role in GE's distribution to joint cavity. Moreover,there was no significant difference between the distribution trend of total three ABS and GE in rats. The pharmacodynamics results showed that the combined administration of ABS and GE has stronger effects on paw swelling,arthritis index and synovial pathomorphology of AA rats than single administration of GE,which suggested that ABS might improve GE's anti-inflammatory effect in AA rats. Based on the above results,ABS has a targeting effect in increasing GE's concentration in joint cavity,with a synergy in efficacy.


Subject(s)
Achyranthes , Chemistry , Animals , Arthritis, Experimental , Drug Therapy , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Pharmacokinetics , Iridoids , Pharmacokinetics , Microdialysis , Rats , Reproducibility of Results , Saponins , Pharmacokinetics , Tandem Mass Spectrometry
14.
Article in Chinese | WPRIM | ID: wpr-774535

ABSTRACT

To observe the effect of Fengshi Qutong Capsules(FSQTC) on angiogenesis of rat aortarings and in knee joint synovium of type Ⅱ collagen-induced arthritis(CIA) rats. The blood vessel of aorta rings of normal SD rats were induced by vascular endothelial growth factor(VEGF) 20 μg·L~(-1 )in vitro, and were treated with FSQTC(0.02, 0.1 and 0.5 μg·L~(-1)) continuously for 9 days. The number, length and area of neovascularization of the vascular ring were measured. SD rats were immunized to establish collagen-induced arthritis. CIA rats were treated with FSQTC(0.25, 0.5, 1 g·kg~(-1)·d~(-1)) and methotrexate(0.2 mg·kg~(-1)·d~(-1)) daily for 19 days. Histopathological examination(HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joint. Immunohistochemistry was performed to observe the expression of platelets-endothelial cell adhesion molecule(CD31), VEGF and VEGF receptor 2(VEGFR_2)in the synovium. Immunofluorescence was performed to observe the expression of CD31 and α smooth muscle actin(αSMA) in synovial membrane.TGF-β, PDGF and VEGFR_2 in serum were detected by enzyme-linked immunosorbent assay. The number, branch length and area of blood vessels of aorta rings were significantly increased induced by VEGF, and FSQTC could significantly reduce the number, branch length and area of blood vessels. Compared with the normal group, the vascular density, CD31 positive expression, CD31~+/αSMA~- immature and total vascular positive expression in the synovial membrane of the model group were significantly increased, and so as VEGF and VEGFR_2 in the synovium. The VEGFR_2, TGF-β and PDGF in sera were also significantly increased in model group. FSQTC reduced the synovial vascular density and inhibited the positive expression of CD31, CD31~+/αSMA~- immature blood vessels and total vascular. FSQTC has no significant effect on CD31~+/αSMA~+mature blood vessels. FSQTC also negatively inhibited the expression of VEGF, VEGFR_2, TGF-β and PDGF in synovial membrane and/or sera. The effect of methotrexate is similar with to the high dose group. Our results demonstrated that FSQTC could inhibit the angiogenesis of synovial tissue in CIA rats and of aortaring in rats, which is related to the reduction of angiogenesis regulatory factor.


Subject(s)
Animals , Aorta , Arthritis, Experimental , Drug Therapy , Capsules , Collagen Type II , Drugs, Chinese Herbal , Pharmacology , Neovascularization, Pathologic , Drug Therapy , Rats , Rats, Sprague-Dawley , Synovial Membrane , Vascular Endothelial Growth Factor A
15.
Article in Chinese | WPRIM | ID: wpr-773698

ABSTRACT

To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 μg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.


Subject(s)
Angiogenesis Inhibitors , Pharmacology , Angiotensin I , Metabolism , Animals , Arthritis, Experimental , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Glycosides , Pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Synovial Membrane , Tablets , Tripterygium , Chemistry , Vascular Endothelial Growth Factor A
16.
Article in Chinese | WPRIM | ID: wpr-773692

ABSTRACT

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets( TG) on the reproductive system of Ⅱ type collagen induced arthritis( CIA) male rats,and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group( Con),model group( CIA),Tripterygium Glycosides Tablets clinical equivalent dose groups of 1,2,4 times( 9,18,36 mg·kg-1),10 rats in each group,and were given by gavage once a day for 42 days after the first immunization.The organ indexes of uterine and ovarian were calculated on days 21 and 42. Histopathological and morphological changes of uterine and ovarian were observed under optical microscope. The concentration of estradiol( E2),follicle-stimulating hormone( FSH),luteinizing hormone( LH),17α-hydroxylase( CYP17 A1) and cytochrome P450 19 A1( CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of uterus and ovary. The results showed that compared with the Con group,CIA group could reduce the number of uterine glands( P<0.05),but no significant changes were observed in other groups. Compared with the CIA group,there were no significant changes in the coefficients of uterus and ovary in the Tripterygium Glycosides Tablets groups. The number of uterine glands,total follicles in the ovary,mature follicles and corpus luteum,the distribution of blood vessels and mitochondria had a certain inhibitory trend,and also slightly increased the number of atresia follicles,but the histopathological quantitative indicators were not statistically different. Except that 2 times clinical dose of Tripterygium Glycosides Tablets could significantly reduce the content of CYP19 A1( P<0. 05) after 42 d administration,there were no significant changes in serum estrogen E2,FSH,LH and estrogen synthesis key enzymes CYP17 A1 in each administration group. Medium and high doses of Tripterygium Glycosides Tablets could increase the expression of apoptotic protein Bax in uterine and ovarian tissues( P<0. 05,P<0. 01),and all the administration groups could inhibit the expression of apoptotic inhibiting protein Bcl-2( P <0. 05,P<0. 01,P<0.001),42 d was more obvious than 21 d. In conclusion,4 times and less than 4 times Tripterygium Glycosides Tablets did not cause obvious toxicity and histopathological changes in the reproductive organs of CIA rats,but it could reduce the level of serum estrogen synthesis key enzyme CYP19 A1 and affect the content of apoptosis-related proteins Bax and Bcl-2 in uterus and ovary tissues. The relevant mechanism needs further study.


Subject(s)
Animals , Apoptosis , Aromatase , Metabolism , Arthritis, Experimental , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Toxicity , Female , Genitalia, Female , Glycosides , Pharmacology , Toxicity , Random Allocation , Rats , Rats, Sprague-Dawley , Tablets , Tripterygium , Chemistry
17.
Article in Chinese | WPRIM | ID: wpr-773690

ABSTRACT

The aim of this paper was to compare the properties of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets from dose-effect-toxicity on type Ⅱ collagen-induced arthritis( CIA) in rats. SD rats were randomly divided into eight groups,including normal group,model group,Tripterygium Glycosides Tablets groups( 1 times equivalent dose 0.009 g·kg-1,4 times equivalent dose 0.036 g·kg-1,16 times equivalent dose 0.144 g·kg-1),Tripterygium wilfordii Tablets groups( 1 times equivalent dose 0.007 5 mg·kg-1,4 times equivalent dose 0.030 mg·kg-1,16 times equivalent dose 0.120 mg·kg-1). Beginning on the first immunization,Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets administered intraperitoneally once a day. After the second immunization,the symptoms such as redness and swelling of joints were observed,and the clinical score and incidence of arthritis were evaluated. HE and Masson staining were used to examine the histopathological changes of joints. The expression level of anti-type Ⅱ collagen antibody Ig G in serum was detected by ELISA,routine testing of blood components,the concentration of ALP( alkaline phosphatase),ALT( alanine aminotransferase),AST( aspartate aminotransferase),GGT( gamma-glutamyltransferase),TBi L( total bilirubin),CRE( creatinine) and UREA( urea) in serum were detected by enzymatic assay. The rate of sperm deformity in the epididymis was evaluated under light microscope. The extent of damage to the testis and ovarian tissue was assessed by HE staining. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets attenuated the inflammation,redness,swelling and deformity of joints and reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile,it also exhibited obvious reduction in all pathological features such as joint synovitis,pannus,cartilage erosion and bone destruction. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets reduced Ig G in a dose-dependent manner,and Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets( P<0.05 or P<0.01). The high doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase the organ coefficient of liver and spleen and reduced RBC and HGB in CIA rats( P<0.01),and severity leading to death. Gastric mucosal injury and morphological changes of liver and kidney were not observed in CIA rats of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets treatment group. The 4 and 16 times doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase serum ALT,GGT and decrease CRE( P<0.05 or P<0.01). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could increase the sperm deformity rate and damage the testicular seminiferous tubules of CIA male rats. Severity increased with dose and time increasing. The effect of Tripterygium Glycosides Tablets( 16 times) is more significant than Tripterygium wilfordii Tablets( 16 times). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets significantly delayed onset of arthritis and inhibited the paw edema and arthritic score. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets also caused male reproductive damage,high dose affected hematopoiesis,and maximum dose leading to death. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets all depended on dose-effect-toxicity manner. Anti-arthritis effect of Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets,but the toxicity of Tripterygium Glycosides Tablets maximum dose is more obvious. The relevant conclusions of our study will provide experimental references for clinical rational use of drugs,and further clinical studies are needed to confirm our conclusions.


Subject(s)
Animals , Arthritis, Experimental , Drug Therapy , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Toxicity , Glycosides , Toxicity , Male , Random Allocation , Rats , Rats, Sprague-Dawley , Tablets , Tripterygium , Toxicity
18.
Article in Chinese | WPRIM | ID: wpr-773556

ABSTRACT

OBJECTIVE@#To investigate the effect of recombinant human PDCD5 (rhPDCD5) treatment in a rat model of bovine II collagen (CII)-induced arthritis (CIA) on inflammatory cytokine secretion, proliferation and apoptosis of activated lymphocytes and explore the mechanisms of rhPDCD5-induced immunosuppression on activated lymphocytes.@*METHODS@#Female Wistar rats were randomly divided into normal control group, CIA+ ovalbumin (OVA) group, CIA+ rhTNFR: Fc group, and CIA+rhPDCD5 group. The rats in the latter 3 groups received intraperitoneal injections of OVA (14 mg/kg), rhTNFR: Fc (3.5 mg/kg) or rhPDCD5 (14 mg/kg) from day 2 to day 26 following CII injection. On day 28, the spleens of the rats were harvested for preparing single cell suspensions of splenocytes, which were activated by CII (20μg/mL) or anti-CD3 (1μg/mL)+ anti-CD28 (2μg/mL) for 48 h and 72 h. The production of interferon-γ(IFN-γ) and interleukin-17A (IL-17A) by the activated lymphocytes was determined by ELISA of the culture supernatants. The proliferation and apoptosis of the activated lymphocytes were assessed using [H]-thymidine incorporation assay and flow cytometry, respectively.@*RESULTS@#Compared with those in CIA + OVA group, IFN-γand IL-17A secretions by the activated lymphocytes from rhPDCD5-treated CIA rats significantly decreased. RhPDCD5 treatment of the CIA rats obviously suppressed the proliferation and promoted apoptosis of the lymphocytes activated by CII or by anti-CD3 + anti-CD28.@*CONCLUSIONS@#rhPDCD5 reduces pro-inflammatory cytokine secretion, inhibits the proliferation and promotes activation-induced cell death of activated CD4 lymphocytes to produce immunosuppression in rat models of CIA.


Subject(s)
Animals , Apoptosis , Apoptosis Regulatory Proteins , Arthritis, Experimental , Cattle , Cell Proliferation , Cytokines , Female , Humans , Lymphocytes , Neoplasm Proteins , Rats , Rats, Wistar
19.
Rev. Soc. Bras. Med. Trop ; 52: e20180043, 2019. graf
Article in English | LILACS | ID: biblio-1041578

ABSTRACT

Abstract INTRODUCTION: Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. This study aimed to evaluate the natural history of Paracoccidioides brasiliensis-induced experimental arthritis of the knee joints in Wistar rats. METHODS: Rats were randomly allocated to either an absolute control group, or 15-day, 45-day, or 90-day experimental (fungus-inoculated) groups. RESULTS: Experimental groups developed classic signs of articular PCM. Titers of anti-gp43 were observed to increase during the interval from 15 to 45 days post-inoculation. CONCLUSIONS: Articular arthritic lesions were induced and progressed during the study period in all experimental groups.


Subject(s)
Animals , Rats , Paracoccidioidomycosis , Arthritis, Experimental/microbiology , Arthritis, Infectious/microbiology , Arthritis, Experimental/pathology , Time Factors , Severity of Illness Index , Arthritis, Infectious/pathology , Rats, Wistar
20.
Article in English | WPRIM | ID: wpr-691350

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect of norcantharidin (NCTD) on collagen-induced arthritis (CIA) rats.</p><p><b>METHODS</b>Sixty Sprague-Dawley(SD) rats were randomly divided into 6 groups (n=10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kg•d)], NCTD middle-dose group [2.7 mg/(kg•d)], NCTD high-dose group [5.4 mg/(kg•d)] and methotrexate (MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin (H&E) staining. The serum levels of interleukin (IL) 1β, IL-6, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), IL-17 and transform growth factor (TGF) β were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression of retinoid-related orphan nuclear receptorγt (RORγt) and forkhead box P3 (Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction.</p><p><b>RESULTS</b>MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats' ankle joints compared with the model group (P<0.05 or P<0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats (P<0.05). Only middle- and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats (P<0.05). However, NCTD has no effect on vascular endothelial growth factor (VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group (P<0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group (P<0.05).</p><p><b>CONCLUSIONS</b>NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.</p>


Subject(s)
Animals , Arthritis, Experimental , Blood , Drug Therapy , Pathology , Bridged Bicyclo Compounds, Heterocyclic , Pharmacology , Therapeutic Uses , Cytokines , Blood , Forkhead Transcription Factors , Metabolism , Joints , Pathology , Male , Nuclear Receptor Subfamily 1, Group F, Member 3 , Metabolism , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley
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