RESUMEN
<p><b>OBJECTIVES</b>To study the effect of Wenhua Juanbi Recipe (, WJR) on expression of receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor receptor superfamily member 14 (TNFRSF14, also known as LIGHT) in rats with collagen-induced arthritis (CIA).</p><p><b>METHODS</b>CIA rats were generated by subcutaneous injection of bovine collagen type-II at the tail base. Sixty CIA rats were randomly assigned (10 animals/group) to: model, methotrexate (MTX)-treated (0.78 mg/kg body weight), and WJR-treated (22.9 g/kg) groups. Healthy normal rats (n=10) were used as the normal control. Treatments or saline were administered once daily by oral gavage. Rats were sacrifificed at day 28 post-treatment and knee synovium and peripheral blood serum were collected. Toe swelling degree and expression of RANKL, OPG, and LIGHT were determined by Western blot and immunohistochemistry.</p><p><b>RESULTS</b>Compared with the normal group, toe swelling degree was signifificantly increased in the model group (P<0.01). After treatment, toe swelling degree decreased signifificantly in the WJR and MTX groups compared with the model group (P<0.01). Compared with the normal group, expression of RANKL and LIGHT were signifificantly increased and OPG signifificantly decreased in peripheral blood and synovium of the model group (P<0.01). Conversely, RANKL and LIGHT expression were signifificantly reduced and OPG increased in the WJR and MTX groups compared with the model group (P<0.01). No statistically significant difference existed between WJR and MTX groups.</p><p><b>CONCLUSION</b>WJR likely acts by reducing RANKL expression and increasing OPG expression, thus inhibiting RANKL/RANK interaction and reducing LIGHT expression, thereby inhibiting osteoclast formation/activation to block bone erosion.</p>
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Animales , Bovinos , Masculino , Artritis Experimental , Quimioterapia , Metabolismo , Western Blotting , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Inmunohistoquímica , Osteoprotegerina , Metabolismo , Ligando RANK , Metabolismo , Ratas Wistar , Miembro 14 de Receptores del Factor de Necrosis Tumoral , Metabolismo , Membrana Sinovial , PatologíaRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of the Chinese medical formula Qubi Zhentong Recipe(, QZR) on the synovial gene expression profile in collagen-induced arthritis (CIA) rats.</p><p><b>METHODS</b>Ten rats were randomly chosen from 60 rats as the control group, and the other 50 rats were used for the CIA models. The CIA model group was constructed by bovine injection of type II collagen through the rats' neck and tail. Twenty rats were randomly chosen from 34 successful CIA models and randomly assigned into two groups: the model group (n =10) and the QZR group (n=10). The QZR group was fed intragastrically with QZR 22.9 g/(kg·d) (10 times the clinical adult dose), and the CIA model group was given the same dose of normal saline. Both model and QZR groups were administered treatment once a day. Total RNA was collected from the knee joint synovium after 30 days. The change in gene expression profile was analyzed by a whole gene chip.</p><p><b>RESULTS</b>A total of 76 genes showed a difference in expression between CIA model group and the control group; 35 genes were down-regulated and 41 were up-regulated. A total of 67 genes showed a difference in expression between the model group and the QZR group; 48 genes were down-regulated and 19 were upregulated.</p><p><b>CONCLUSIONS</b>QZR may affect CIA by stimulating multiple genes and targets, which are related to oncogenes, apoptosis, metabolism, the immune system, ion channels, and transport proteins.</p>
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Animales , Bovinos , Masculino , Ratas , Artritis Experimental , Genética , Modelos Animales de Enfermedad , Regulación hacia Abajo , Genética , Medicamentos Herbarios Chinos , Farmacología , Electroforesis en Gel de Agar , Extremidades , Patología , Regulación de la Expresión Génica , Ratas Wistar , Membrana Sinovial , Metabolismo , Patología , Transcriptoma , Regulación hacia Arriba , GenéticaRESUMEN
<p><b>OBJECTIVE</b>To study the effect of Wenhua Juanbi Recipe (WJR) on proliferation and apoptosis of synoviocytes in rats with collagen-inducing arthritis (CIA).</p><p><b>METHODS</b>A CIA model was induced by intradermal injection of bovine collagen type II emulsion at the base of rat tails. Thirty modeled healthy Wistar rats were randomly assigned to one of three groups (10 per group): the model group, the methotrexate (MTX)-treated group (0.78 mg/kg) and the WJR-treated group (22.9 g/kg). A group of 10 healthy rats was used as normal control. Treatments or normal saline for the control group were administered by oral gavage once daily. Rats were sacrificed after 30-day treatment and subjected to the following examinations: arthritis index (AI) was estimated, inflammatory cell infiltration and proliferation in synovial membrane were evaluated by microscopy, the synoviocyte apoptosis was determined by TUNEL assay, and the cell apoptosis index was calculated.</p><p><b>RESULTS</b>AI was lowered significantly in the WJR group compared to the model group (P<0.01). The pathological findings observed in the model group were reversed in the WJR group, including increase in inflammatory cell infiltration and synoviocyte proliferation in synovial membrane and reduction in cell apoptosis index (all P<0.01).</p><p><b>CONCLUSIONS</b>Synoviocyte proliferation and apoptosis reduction were present in CIA rats. WJR was effective in treating the rat model of CIA. The therapeutic effect might be exerted through inducing apoptosis and suppressing proliferation of synoviocytes.</p>
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Animales , Bovinos , Masculino , Ratas , Apoptosis , Artritis Experimental , Patología , Proliferación Celular , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Ratas Wistar , Membrana Sinovial , PatologíaRESUMEN
<p><b>OBJECTIVE</b>To research the effects of Qubi Zhentong Recipe (QZR) on the expressions of interleukin-1beta (IL-1beta), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) in the synovial of rats with collagen-inducing arthritis (CIA), and to discuss its mechanisms of action.</p><p><b>METHODS</b>Healthy male Wistar rats were recruited and randomly divided into the model group ( n = 50) and the normal control group (n = 10). Rats of the model group were injected with type II collagen of bovine (BC II) emulsion in the tail and nape to establish the CIA model. After successful modeling, 30 successfully modeled rats were selected and randomly divided into three groups, i.e., the model group (n = 10), the QZR group (n = 10), and the methotrexate (MTX) group (n = 10). Rats in the normal control group and the model group were administered with physiological saline by gastrogavage, while those in the QZR group were administered with QZR at 22.9 g/kg by gastrogavage. All medication was performed once daily. The rats in the MTX group were administered with MTX suspension at 0.78 mg/kg by gastrogavage, once per week. After 30-day treatment, the levels of IL-1beta, IL-8, and VEGF in the synovial were detected by immunohistochemical method. The arthritis index (AI) was scored before and after medication.</p><p><b>RESULTS</b>After treatment the AL score of the QZR group and the MTX group was obviously lower than that of the model group (P < 0.01). The AI score of the two drug groups were lower than that before treatment (P < 0.01). Compared with the normal control group, the expression levels of IL-1beta, IL-8, and VEGF obviously increased in the model group (P < 0.01). Compared with the model group, the expression levels of IL-1beta, IL-8, and VEGF were significantly lower in the two drug groups (P < 0.01). But there was no statistical difference between the QZR group and the MTX group (P > 0.05).</p><p><b>CONCLUSION</b>Decreasing the expression levels of IL-1beta, IL-8, and VEGF in the synovial of CIA rats may be one of the mechanisms for treating CIA by QZR.</p>
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Animales , Masculino , Ratas , Artritis Experimental , Quimioterapia , Metabolismo , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Interleucina-1beta , Metabolismo , Interleucina-8 , Metabolismo , Ratas Wistar , Membrana Sinovial , Metabolismo , Factor A de Crecimiento Endotelial Vascular , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To study the effects of Wenhua Juanbi recipe (WJR) on the gene expression profile of the synovium in collagen-induced arthritis (CIA) rats, and to explore its mechanisms for treating CIA.</p><p><b>METHODS</b>The CIA model was induced by intradermal injection of bovine collagen type II emulsion from the tail of 40 healthy male Wistar rats. Selected 16 successfully modeled rats were randomly divided into the model group and the WJR-treated group, 8 in each group. WJR at the daily dose of 22.9 g/kg was given to rats in the WJR-treated group by gastrogavage, while normal saline was given to those in the model group. Both were performed once daily, for 30 successive days. By the end of medication, the total RNA was extracted from the synovium of rats in the two groups. The gene expression profile of each sample was analyzed using Illumina oligonucleotide microarray.</p><p><b>RESULTS</b>Compared with the model group, after the intervention of WJR, 222 differentially expressed genes were identified in CIA rats, including 76 genes up-regulated (such as RatNP-3b and so on) and 146 downregulated (such as Angptl 2, Muc1, bcl-2, and so on). The differential genes were mainly involved with apoptosis, angiopoietin, defensin gene, cytokine, signal transduction, oncogene, etc.</p><p><b>CONCLUSION</b>WJR played a role in treating CIA multi-target possibly through regulating and controlling multiple genes expressions. Wenhua Juanbi Recipe; collagen-induced arthritis; synovium; gene expression</p>
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Animales , Masculino , Ratas , Artritis Experimental , Quimioterapia , Genética , Metabolismo , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Expresión Génica , Perfilación de la Expresión Génica , Ratas Wistar , Membrana Sinovial , Metabolismo , TranscriptomaRESUMEN
<p><b>OBJECTIVE</b>To observe the clinical effect of Wenhua Juanbi Recipe (WJR) in treating rheumatoid arthritis (RA), its effects in reducing the dosage of Western medicine used and stabilizing condition of disease, as well as its influences on peripheral blood levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and anti-cyclic citrullinated peptide antibody (anti-CCP), for the sake of exploring its preliminary acting mechanism.</p><p><b>METHODS</b>One hundred patients with RA were randomly assigned to 2 groups, the control group and the treated group, 50 in each group. All were treated with oral administration of methotrexate (MTX,7.5 mg per week), sulfasalazine (0.5 g, tid) and meloxicam (Mobic, 7.5 mg, bid), but to the treated group WJR was given additionally. The therapeutic course for both groups was 3 months. Clinical effect, changes of symptoms and physical signs, dosages of western medicines used, and laboratory indices in 2 groups after treatment were observed, and cases of relapse 3 months after treatment were figured out.</p><p><b>RESULTS</b>The total effective rate in the treated group was higher than that in the control group (88.0% vs 76.0%, P<0.05). The improvements in scores of symptoms and signs [joint pain (0.61 +/- 0.59), swelling (1.49 +/- 1.20), tenderness (0.90 +/- 0.69), movement (0.68 +/- 0.62), griping strength (68.56 +/- 6.50) mm Hg, morning stiff time (23.26 +/- 9.26) min], and in levels of laboratory indices (TNF-alpha, IL-1beta, anti-CCP, RF, ESR, CRP, PLT and Ig) in the treated group after treatment were significantly superior to those in the control group (P<0.05 or P<0.01). The dosages of MTX [(82.11 +/- 11.35) mg vs (94.75 +/- 10.23) mg] and meloxicam [(108.85 +/- 16.13) mg vs (189.63 +/- 18.44) mg] used, and the relapse rate in the treated group were lower significantly (P<0.05, P<0.01) than those in the control group respectively.</p><p><b>CONCLUSIONS</b>Effect of combined therapy of WJR and Western medicines is superior to that of using Western medicines alone in treating RA; WJR can reduce the dosages of Western medicines used and the relapse rate, as well as stabilize the condition of illness. It has the effects of immune regulating and anti-inflammatory reaction. Its mechanism for treating RA is possibly the inhibition on cytokines of TNF-alpha and IL-1beta.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Artritis Reumatoide , Sangre , Quimioterapia , Quimioterapia Combinada , Medicamentos Herbarios Chinos , Usos Terapéuticos , Interleucina-1beta , Sangre , Metotrexato , Usos Terapéuticos , Fitoterapia , Tiazinas , Usos Terapéuticos , Tiazoles , Usos Terapéuticos , Factor de Necrosis Tumoral alfa , SangreRESUMEN
<p><b>OBJECTIVE</b>To study the effect on apoptotic of CD4+ T, CD19+ B in spleen of BXSB mice with systemic lupus erythematosus treated with Langchuangjing Granule and to probe into the mechanism of treatment.</p><p><b>METHODS</b>The apoptosis was examined by the flow cytometric analysis and immunofluorescence double-staining method.</p><p><b>RESULTS</b>Apoptosis of male BXSB mice speeds up. Langchuangjing Granule can restrain the excessive apoptosis of CD4+ T and CD19+ B cells in spleen.</p><p><b>CONCLUSION</b>Langchuangjing Granule treated systemic lupus erythematosus by restraining the excessive apoptotic of T, B lymphocytes, probably restraining the release of excessive amount of apoptotic DNA fragments, so decreasing abnormal proliferation of B cells and the produce of autoantibodies.</p>
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Animales , Femenino , Masculino , Ratones , Antígenos CD19 , Apoptosis , Linfocitos B , Patología , Linfocitos T CD4-Positivos , Patología , Medicamentos Herbarios Chinos , Farmacología , Lupus Eritematoso Sistémico , Alergia e Inmunología , Patología , Ratones Endogámicos , Distribución Aleatoria , Bazo , PatologíaRESUMEN
Objective To explore the correlation between anti-cyclic citrullinated peptide(A-CCP) antibody and tumor necrosis factor(TNF)-?, rheumatoid factor(RF), ESR, PLT count and clinical features in patients with rheumatoid arthritis(RA), and the outcome of unclassified arthritis(arthralgia)patients after six months follow up. The value of A-CCP antibdy in the diagnosis of early RA and its pathogenetic roles is in- vestigated. Methods A-CCP antibody and TNF-?were detected by ELISA and the RF was tested by the rate scatting immunity method in 91 RA patients, 46 unclassified arthritis(arthralgia)patients and 45 other rheumatic diseases patients. Results A-CCP antibody levels in serum correlated significantly with TNF-?levels, PLT count and the degree of joint swelling in RA and unclassified arthritis(arthralgia)patients(r= 0.854, P=0.O00; r=0.882, P=0.000; r=0.318, P=0.002; r=0.486, P=0.001; r=0.291, P=0.005; r=0.731, P= 0.000 respectively). A-CCP antibody levels in serum was weakly negatively correlated with the gripping power in RA patients(r=0.228, P=0.030). And it was weakly correlated with ESR in unclassified arthritis(arthrai- gia)patients(r=0.365, P=0.013). Compared with other rheumatic diseases patients, A-CCP antibody levlels in serum increased significantly in RA and unclassified arthritis(arthralgia)patients(P=0.000). Compared with normal controls, it increased in other rheumatic diseases patients(P=0.011). Twenty-four patients had positive A-CCP antibody in 46 unclassified arthritis(arthralgia)patients. Thirty-two out of 46 unclassified arthritis(arthralgia)patients were early RA after 6 monthes follow up. 95.8%(23/24)unclassified arthritis (arthralgia)patients with positive A-CCP antibody were early RA. Conclusion A-CCP antibody reflects disease activity in certain extent. It's benefit to the diagnosis of early RA. High A-CCPantibody levels com- bined with high levels of TNF-?, ESR, PLT count and joint swelling can help the diagnosis of early RA.