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OBJECTIVE@#To observe the effects of moxibustion on the ultrastructure of synovial cells of knee joint and serum cytokines in adjuvant arthritis (AA) rats, and to explore the potential mechanism of moxibustion in treatment of rheumatoid arthritis.@*METHODS@#Forty-five Wistar male rats were randomly divided into a normal group, a model group and a moxibustion group, with 15 rats in each group. In the model group and the moxibustion group, the AA model was replicated under wind, cold and humid environment and by injection with complete freund's adjuvant. In the moxibustion group, moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) was used, 20 min each time, once daily, for consecutive 21 days. In the normal group and the model group, no intervention was processed. The scores of the knee joint swelling degree (JSD) and arthritis index (AI) were compared among groups. The ultrastructure of synovial cells of knee joint were observed under transmission electron microscope (TEM). The levels of serum cytokines such as tumor necrosis factor-α (TNF-α), interieukin (IL)-1β, IL-6 and IL-10 were detected using ELISA method.@*RESULTS@#Compared with the normal group, JSD and AI scores, the levels of TNF-α, IL-1β and IL-6 were increased (P<0.01), while IL-10 was reduced (P<0.01) in the model group after intervention. JSD and AI scores, and the levels of TNF-α, IL-1β and IL-6 were lower (P<0.05, P<0.01), while the level of IL-10 was higher (P<0.01) in the moxibustion group compared with the model group. Compared with the normal group, the ultrastructure of synovial cell was obviously damaged in the model group, and the damage was attenuated in the moxibustion group compared with the model group.@*CONCLUSION@#Moxibustion can reduce the symptoms of arthritis in AA rats, which may be related to the improvement of the ultrastructure of synovial cells and the regulation of cytokines.
Subject(s)
Male , Rats , Animals , Cytokines , Interleukin-10 , Arthritis, Experimental , Tumor Necrosis Factor-alpha , Interleukin-6 , Moxibustion , Rats, Wistar , Knee JointABSTRACT
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 , Rats , Arthritis, Experimental/therapy , Arthritis, Rheumatoid , Gastrointestinal Microbiome , Moxibustion , Rats, WistarABSTRACT
Objective:To observe the effect of Danggui Niantongtang on the protein and mRNA expression of key regulatory factors of the extrinsic and intrinsic apoptotic pathway in synovial tissue of adjuvant arthritis （AA） rats， and to further explore the mechanism of Danggui Niantongtang in the prevention and treatment of rheumatoid arthritis. Method:The general condition of AA rats， including its body weight， were observed. The changes of toe volume were detected by toe volume meter. Histopathological changes of synovium of knee joint were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expression levels of tumor necrosis factor receptor super family 6 （Fas）， Fas-associating protein with a novel death domain（FADD）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cysteinyl aspartate specific proteinase Caspase-3 （Caspase-3） were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with the normal group， the toe volume of the model group increased significantly （<italic>P</italic><0.01）， with significantly proliferated synovial cells， significantly reduced mRNA and protein expression levels of Fas， FADD， Bax and Caspase-3 in synovial tissues（<italic>P</italic><0.05，<italic> P</italic><0.01）， and significantly increased Bcl-2 level （<italic>P</italic><0.01）. Compared with the model group， the swelling degree of toes in Danggui Niantongtang group and Tripterygium group was significantly alleviated （<italic>P</italic><0.01）， with significantly improved synovial hyperplasia， significantly increased mRNA and protein expression levels of Fas， FADD， Bax and Caspase-3 （<italic>P</italic><0.05， <italic>P</italic><0.01）， and significantly decreased expression levels of bcl-2 mRNA and protein （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Danggui Niantongtang can effectively reduce joint swelling and abnormal proliferation of synovial tissue in AA rats. Its mechanism may be related to regulating the expression of Fas， FADD， Bax， Bcl-2 and Caspase-3， and promoting the apoptosis of synovial cells.
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Objective:To study the protective effect and mechanism of Chaenomelis Fructus alcohol extract (CFE) on the synovium of rheumatoid arthritis (RA). Method:Sixty male SD rats were randomly divided into normal group and model group. RA model was made by injection of complete Freund's adjuvant， and then was randomly divided into model group， CFE low， medium and high dose group and Tripterygium glycoside group according to the inflammatory score. The CFE groups (0.15，0.30，0.60 g·kg-1·d-1) had intragastric administration once a day for 30 d after the model establishment. The blank control group and the model group were given the same volume saline water by gavage. After all the drugs were given， the blood， joint tissues and synovium tissue of rats were collected. The levels of interleukin-1β (IL-1β)， interleukin-6 (IL-6)， interleukin-10 (IL-10) and tumor necrosis factor (TNF)-α in serum were detected by enzyme linked immunosorbent assay (ELISA)， the pathological changes of synovium were observed by hematoxylin eosin (HE) staining， and the expressions of B-cell lymphoma-2 (Bcl-2)，Bcl-2 associated X protein (Bax) and death factor (Fas) in joints were detected by Western blot. Result:Compared with normal group， the swelling degree and inflammation index of rats' feet in model group increased significantly， the levels of inflammatory factors IL-1β， IL-6， TNF-α in serum increased (P<0.01)， anti-inflammatory factor IL-10 decreased (P<0.01)， the protein expression of Bax， Fas and Bcl-2 increased， and the statistical results of Bcl-2 showed significant difference (P<0.05). Compared with model group， the swelling degree and inflammatory index of the plantar of RA rats were improved in the middle and high dose groups of CFE (P<0.01)， the pathological changes such as synovial tissue hyperplasia and inflammatory cell infiltration were reduced in each dose group， and the levels of IL-1β， IL-6 and TNF-α in serum were reduced (P<0.05)， anti inflammatory factor IL-10 increased (P<0.05)， the disorder of inflammatory cytokine in the model was corrected， Bax， Fas expression increased， Bcl-2 protein expression decreased (P<0.01). Conclusion:CFE can reduce the degree of inflammation in RA joint and has obvious anti RA effects， which may be related to the apoptosis of synoviocytes induced by CFE.
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Boswellia serrata is an Indian herb known for its potent anti-inflammatory and anti-arthritic properties in ancient folk medicine. The present study was undertaken to evaluate the anti-arthritic potential of Boswellia serrata on radiographic joint damage and histopathology of adjuvant-induced arthritis. Thirty male Wistar rats were randomly divided into 5 groups with six rats each. While group 1 served as normal control, arthritis was induced in animals belonging to groups 2 (arthritic control); 3, 4 and 5 (treatment groups) by injecting 0.1 ml of Freund’s complete adjuvant, intradermally into the hind foot pad. Treatment protocol was followed from 3rd to 21st day, with Boswellia serrata given orally as methanolic extract @ 500 mg/kg b.wt. to group 3, meloxicam given subcutaneously @1 mg/kg b.wt. to group 4 and both the drugs given concurrently to group 5. The onset and progression of arthritis were assessed weekly by radiographic interpretation. The drug effects were evaluated on the histopathology after completion of the experiment. The extent of paw inflammation before treatment and its subsequent amelioration after treatment were noticed in groups 3, 4 and 5 Boswellia serrata showed better amelioration compared to meloxicam with a superior curative effect witnessed when both the drugs were administered together. The significant alleviation of joint damage in adjuvant-induced arthritis may be attributed to the pharmacologically active principles present in the extracts of Boswellia serrata
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OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Xuanzhong" (GB39) on joint inflammatory reactions and serum matrix metalloproteinase-3 (MMP-3) and MMP-9 contents in rats with adjuvant arthritis (AA), so as to explore its mechanism underlying improvement of AA. METHODS: Forty male SD rats were randomly divided into control, model, acupoint and non-acupoint groups (n=10 in each group). The arthritis model was established by hypodermic injection of complete Freund's adjuvant (0.1 mL) into the bilateral footpads. EA (2 Hz, 3 V) was applied to bilateral ST36 and GB39 or two non-acupoints (5 mm left to ST36 and GB39) for 15 min, once every other day for a total of 8 times. The arthritis index score was evaluated according to the severity of local erythema and swelling of the ankle joint, plantar joint, toe joint and foot metacarpal joint (0-4 points). The inflammatory conditions of the ankle joint were observed by H.E. staining, and the contents of serum MMP-3 and MMP-9 were assayed by ELISA. RESULTS: The arthritis index score and serum concentrations of MMP-3 and MMP-9 were significantly increased in the model group relevant to the control group (P<0.01), and obviously decreased after EA intervention on the 18th day (P<0.01). The therapeutic effect of acupoint EA was notably superior to non-acupoint EA in down-regulating the arthritis index score and serum MMP-3 and MMP-9 concentrations (P<0.01). Under light microscope, marked proliferation of the synovial cells, inflammatory cell infiltration and increase of newly blood vessels were observed in the ankle joint of the model group, which was relatively milder in the acupoint group. CONCLUSION: acupoint EA intervention can significantly alleviate the inflammatory reaction of AA rats, which may be related to its effects in reducing the levels of serum MMP-3 and MMP-9.
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Objective:To investigate the effect of Gancao Fuzitang on the proliferation of fibroblast-like synoviocytes (FLS) in synovial tissue of mice with adjuvant-induced arthritis (AA). Method:The 48 male Balb/c mice were randomly divided into 4 groups:normal control group, model group(arthritis induced through injection with adjuvant), Gancao Fuzitang group and triptolide group. The normal control group and the model control group were orally given physiological saline. After the successful modeling, the mice of the other two groups were treated with Gancao Fuzitang or triptolide orally for 18 days. Then the animals were euthanized, the paw edema of the animals was measured, and arthritic ankles were observed by histological examination. Tumor necrosis factor (TNF)-α was examined by immunoassays. The proliferation of synovial cells of foot joints was detected by immunohistochemical expressions of Vimentin. The expressions of Cyclin D1, proliferating cell nuclear antigen (PCNA), p53 and p21 were detected by Western blot. Result:Compared with the normal control group, the mice of synovial hyperplasia and bone erosion in model group were obvious. The joint swelling degree, TNF-α level and proliferation of FLS were increased (P1,PCNA were up-regulated(PPα, cell cycles (Cyclin D1 and PCNA), and increased protein expressions of p53 and p21 (PConclusion:Gancao Fuzitang has a therapeutic effect on AA mice, and the mechanism might be associated with its anti-inflammatory effect and the effects in regulating Cyclin D1, PCNA, p53 and p21 expressions and inhibiting FLS proliferation.
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OBJECTIVE： To investigate the therapeutic effect of Licorice and aconite decoction in the treatment of adjuvant arthritis （AA） model mice through anti-synovial angiogenesis pathway. METHODS： Totally 48 male Balb/c mice were randomly divided into normal group， model group， Licorice and aconite decoction group and tripterygium glycosides group （positive drug group）， with 12 mice in each group. Except for normal group， AA model was established by intradermal injection of Freund’s complete adjuvant into the left hind toe of mice. 12 d after modeling， normal group and model group were given same volume of water intragastrically； Licorice and aconite decoction group （7.8 g/kg，by total amount of crude drug） and tripterygium glycosides group （0.01 g/kg） were given relevant medicine 20 mL/kg intragastrically， once a day， for consecutive 18 d. The joint lesions of mice were observed and recorded， and the foot swelling degree of mice was measured by water volume method. HE staining was used to observe the pathological change of ankle joint in mice. The protein levels of platelet endothelial cell adhesion molecule-1 （CD31） and vascular endothelial growth factor （VEGF） were determined by immunofluorescence assay. The protein expressions of nuclear factor κB（NF-κB） and zinc finger transcription factor GATA4 （GATA4） were detected by Western blotting assay. RESULTS： Compared with normal group， ankle joint of model group mice was markedly reddened and swollen， and foot swelling degree increased significantly （P＜0.05）. Synovial tissue of ankle joint proliferated， pannus increased significantly， and a large number of inflammatory cells and joint erosion were observed. The protein expression of CD31， VEGF， NF-κB and GATA4 in synovial tissue of mice were increased significantly （P＜0.05）. Compared with model group， the redness and swelling of ankle joint in mice were alleviated， and the foot swelling degree was significantly reduced in Licorice and aconite decoction group （P＜0.05）. Pannus in synovial tissue decreased and other pathological symptoms were improved. The protein expression of CD31， VEGF， NF-κB and GATA4 were decreased significantly in synovial tissue （P＜0.05）. CONCLUSIONS： Licorice and aconite decoction can decrease the protein expression of VEGF，NF-κB and GATA4 in synovial tissue， reduce the generation of pannus in synovial tissue and effectively inhibit the angiogenesis in synovial tissue so as to prevent bone destruction and protect joint of AA model mice.
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AIM To study the anti-inflammatory effects of compound Cervi Cornu Degelatinatum extract on adjuvant arthritic rats.METHODS The rats,except for those assigned into a blank group,were induced to be the adjuvant arthritis models by Freund's complete adjuvant and randomly divided into model group,Prednisone Acetate Tablets group,Tripterygium wilfordii polyglycoside tablets group,and compound Cervi Cornu Degelatinatum extract groups (1 000 mg/kg high-dose group,500 mg/kg medium-dose group,and 250 mg/kg low-dose group) to observe changes in body weight,mental state,and extent of joints injury.Post-treatment levels of TNF-α,IL-6,IL-10 and PGE-2 were determined by ELISA,and the pathological changes of ankle joints were assessed by HE staining.RESULTS Significantly lower body weight and IL-10 level,markedly higher levels of TNF-α,IL-6,PGE-2,and joints injury in the model group than those in the blank group were observed (P ＜0.01).Such indices also revealed the significant superiority in the high-dose,medium-dose groups of compound Cervi Cornu Degelatinatum extract and the positive control group as compared with the model group.CONCLUSION Compound Cervi Cornu Degelatinatum extract highlights the rheumatoid arthritis management through proinflammatory cytokines secretion reduction,the antiinflammatory factors improvement,and the inflammatory reaction and tissue damage alleviation.
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Aim To observe the expression of CXCL12 and its receptor CXCR4 in spleen of rats with adjuvant-induced arthritis (AA) and the effects of paeoniflorin-6′-O-benzene sulfonate (CP-25). Methods AA rats were induced using complete Freund's adjuvant and were randomly divided into normal group,AA group, CP-25 group (50 mg·kg-1) and methotrexate group (MTX,0.5 mg·kg-1),which were treated from d 14 to d 28. HE staining was used to assess the pathologi-cal changes of spleen. The expression of CXCL12 and CXCR4 in spleen was detected by ELISA,immunohis-tochemitry and Western blot. Results CP-25 (50 mg ·kg-1)alleviated the pathological changes of spleen and decreased the expression of CXCL12 and CXCR4 in spleen of AA rats. The pathological changes of spleen and the expression of CXCL12/CXCR4 in spleen revealed a positive correlation. Conclusions Increased expression of CXCL12 and its receptor CX-CR4 may be associated with the pathological changes of spleen in AA rats,which plays an important role in the pathogenesis of RA. CP-25 has obvious therapeutic effect on AA rats and its mechanism may be related to the inhibition of the expression of CXCL12 and CXCR4 in the spleen.
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Aim To observe the expression of mesen-cephalic astrocyte-derived neurotrophic factor(MANF) in synovial membrane and serum of rats with adjuvant arthritis (AA) and to analyse the relationship between MANF expression and arthritis. Methods AA models were prepared by injecting Freund complete adjuvant (FCA) into SD rats. The swelling of the secondary joint was measured by foot volume measurement. The severity of AA was recorded by arthritis index (AI). Synovial pathological changes were observed by HE staining. The protein and mRNA levels of MANF,BiP and CHOP extracted from synovial tissues in different periods of AA rats were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The levels of MANF, C-reactive protein (CRP), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in serum were detected by enzyme-linked immunosorbent assay (ELISA) and then the relationship between MANF level and inflam-matory factors were explored. Results AA rat model was established successfully. The expression of BiP significantly increased in synovial tissue on d 2 after CFA injection,and decreased until d 28. The expres-sion of MANF slightly increased on d 2,then remained stable,and significantly increased on d 14, and then decreased gradually. The expression of CHOP kept to rise slowly at a low level. The level of MANF in serum markedly increased on d 14,then gradually decreased, but it was still higher than the normal level on d 28. The level of CRP exhibited similar trend with MANF. Correlation analysis showed that MANF had a negative correlation with arthritis symptoms, IL-1β and TNF-α in the secondary inflammatory period of AA rats. Con-clusions Arthritis induces the expression and secre-tion of MANF,and the level of MANF is closely relat-ed to the progression and severity of arthritis.
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Objective To explore the effects of carboxyamidotriazole (CAI) on cytokines production by peritoneal macrophages from adjuvant arthritis(AA) rats in vitro. Methods Freund's completed adjuvant was used to induce AA in rats.Peritoneal macrophages were prepared from asepsis and incubated with CAI(10,20,40 μmol/L).The contents of TNF-α,IL-1β and IL-6 in the culture supernatant were measured by ELISA,and mRNA expressions of TNF-α,IL-1β and IL-6 were determined by real-time quantitative PCR.NF-κB p65 DNA binding activity in the nu-clear protein was detected with TransAM kit. Results The level of TNF-α,IL-1β and IL-6 in the culture superna-tant, their intracellular mRNA expression and NF-κB p65 DNA-binding activity in peritoneal macrophages of AA rats were significantly inhibited by CAI (20 and 40 μmol/L) (P<0.05 and P<0.01).Conclusions CAI may de-crease the production of pro-inflammatory cytokines such as TNF-α,IL-1β and IL-6 through inhibiting the activa-tion of NF-κB,which is potentially associated with its anti-arthritic mechanisms.
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Objective:To investigate the effect of total saponins from Clematis florida Thunb. on rat model of adjuvant arthritis ( AA) . Methods:Wistar rats were randomly divided into six groups:the normal control group, the model control group, the positive control group ( indomethacin, 10 mg?kg-1 ) , high, medium and low dose groups of total saponins from Clematis florida Thunb. with ten rats in each group. The rat model of AA was established with Freund's complete adjuvant and the effects of drugs on body weight and foot swelling of AA rats were observed. After the animals were sacrificed, the serum levels of superoxide dismutase ( SOD) , mal-onaldehyde ( MDA) , nitric oxide ( NO) and glutathion peroxidase ( GSH-PX) were determined. The serum levels of interleukin-8 ( IL-8), IL-10 and tumor necrosis factor-α(TNF-α) were detected by ELISA. Results:On the 8th day of drug administration, total sapo-nins from Clematis florida Thunb. could effectively alleviate the changes in the body weight and foot swelling of the rats to a certain ex-tent when compared with the model control group (P <0. 05 or P <0. 01). There were no significant differences between the high dose group and the positive control group (P>0. 05), and there were significant differences between the low dose group and the high/medium dose groups (P<0. 05). The levels of SOD, MDA, NO and GSH-PX in serum of AA rats were significantly affected by the total saponins from Clematis florida Thunb. . Except for NO indicator of low dose group, the differences between the other groups and the model control group were statistically significant (P<0. 05 or P<0. 01), and there were significant differences in MDA, NO and GSH-PX levels between high dose group and low dose group (P<0. 05). Compared with those in the model control group, the serum levels of IL-8 and TNF-αin each total saponins from Clematis florida Thunb. group significantly decreased and the content of IL-10 sig-nificantly increased (P<0. 05 or P<0. 01). There was no significant differences in the levels of IL-10 and TNF-α between the high dose group and the positive control group (P>0. 05), and the differences in IL-8 and IL-10 between high dose group and low dose group were statistically significant (P<0. 05). Conclusion: The total saponins from Clematis florida Thunb. have good therapeutic effect on AA, and the underlying mechanism may be related to the reduction of lipid peroxidation and the inhibition of pro-inflammatory cytokines.
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Objective To establish and evaluate a rat model presenting symptoms of arthritis-hypertension disease (AHD).Methods A total of forty healthy 5-6 week-old male SD rats were used in this study.Hypertension was induced by constriction of the left renal artery by two kidney one clip (2K1C) with a 0.25 mm silver clamp, and AHD model was established by injecting 0.1 mL complete Freund adjuvant to the left hind paw.Tail artery pressure was measured with a non-invasive blood pressure measurement system.The degree of swelling in the non-inflammatory joint of rats was measured with a paw volume measuring instrument, the arthritis index and incidence of inflammation were evaluated.The rats were sacrificed on the 35th day.The thoracic aorta, ankle joint and spleen tissues were examined by pathology using HE staining.Results The joint of AHD model rat was significantly swollen, extensive synovial cell hyperplasia, inflammatory cell infiltration, vascular pannus formation, and bone and cartilage destruction.The number of germinal centers in spleen was increased, and a large number of lymphocyte infiltration, diffuse proliferation of white pulp, and red pulp infiltration were present.The arthritis index, incidence of inflammation and histopathological scores of the joint and spleen were significantly higher than adjuvant arthritis (AA) rats;meanwhile, the blood pressure of AHD model rat was significantly increased, the thickness and cross-sectional area of thoracic aorta were significantly increased, while the lumen diameter was significantly reduced.The blood pressure and vascular injury were significantly increased or aggravated compared with the HT rats.Conclusions A rat model of arthritis-hypertension disease is successfully established by using complete Freund adjuvant intradermal injection to the footpad and surgery to narrow the left renal artery.
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AIM To observe the effects of Wuwei Wentong Chubi Capsules (Cinnamomi Ramulus,Poria,Epimedii Folium,etc.) on autophagy proteins of Beclin-1 and LC3-Ⅱ in adjuvant-induced arthritis rats and to explore the possible mechanism of action.METHODS Sixty SD rats were randomized into six groups:normal group,model group,Wuwei Wentong Chubi Capsules (0.8,1.6,3.2 g/kg) groups and tripterygium glycosides (TPT,40 mg/kg) group.In addition to the normal group,adjuvant arthritis (AA) was induced with Freund's complete adjuvant.From the 2th day after injection of FCA,Wuwei Wentong Chubi Capsules with different doses and TPT were given by gavage once a day for 12 days.At the end of the experiment,ankle-joint samples were taken to examine the degree of AA by HE.Beclin-1 and LC3-Ⅱ mRNA were determined by real-time fluorescent quantitative PCR.Meanwhile,the protein expression levels of Beclin-1 and LC3-Ⅱ were determined by immunofluorescence histochemical staining and Western blot.RESULTS As compared with the model group,Wuwei Wentong Chubi Capsules (1.60,3.20 g/kg) not only significantly reduced histopathological injuries,but also effectively up-regulated mRNA and protein expressions of Beclin-1 and LC3-Ⅱ.CONCLUSION Wuwei Wentong Chubi Capsules has a therapeutic action on AA in rats,which might be partly associated with promoting autophagy,decreasing excessive proliferation of synovial cells,leading to the reduction of damage to articular cartilage.
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Objective:To observe the effect of Xinfeng Capsule (XFC) on synovial membrane PI3K/AKT/mTOR pathway in adjuvant arthritis (AA) rats.Methods:Rats were randomly divided into normal control group,model control group,methotrexate group,tripterygium glycoside group and XFC group.The expressions of IL-6,IL-10,HIF-1α and VEGF-A were detected by immunohistochemical method,and the expressions of PI3K,AKT1 and p-AKT1 were detected by immunoblotting.Results:Expression of AKT1,mTOR and ES proteins in synovial blood vessels.The expression of IL-6,VEGF,HIF-1α and synovial membrane PI3K,AKT1,p-AKT1,mTOR,ES in the model group were significantly higher than those in the control group The expression of PI3K,p-AKT1,mTOR,ES in synovial membrane decreased,and IL-10 in serum increased in XFC group,and the expression of HIF-1α,IL-6 and VEGF-A were decreased.Conclusion:XFC can improve angiogenesis in AA synovium by regulating PI3K/AKT/mTOR signaling pathway,HIF-1α and ES expression.
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OBJECTIVE: To study the pharmacological function of the petroleum ether extract from Citrullus lanatus vine (PEECLV) in treating adjuvant arthritis(AA) and explore the mechanism. METHODS: AA in mice was made to observe the anti-inflammatory effect of PEECLV. Arthritis index was calculated by 5 grades evaluation. Thymus and spleen index were measured. The content of RF, PGE2, COX-1, COX-2 in serum were measured. The levels of TNF-α, IL-1β in serum were measured. RESULTS: PEECLV can suppress the foot swelling degree in model mice. It can increase thymus index, reduce spleen index and AI of AA in mice. High-dose group can significantly reduce serum PGE2, IL-1β, COX-2 and COX-1 levels in AA in mice. All groups can reduce TNF-α and RF levels. CONCLUSION: PEECLV has a certain degree therapeutic effect on AA, and the possible mechanism is to affect the production of inflammatory mediators and antioxidant.
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Objective: To observe the inhibition effect of sorafenib on adjuvant arthritis in rats. Methods: A total of 36 male SPF SD rats were divided into 6 groups and 0. 1 ml of the complete Freund' s adjuvant was subcutaneously injected into the left hind paw except the normal group. The volume of rat hind paw was measured. The CD4+ and CD8+ T cell subsets of the peripheral blood were analyzed by flow cytometry. The microvessel density of synovial tissues was determined by immunohistochemical chain mildew avidin peroxidase enzymatic (SP) method. Results: Compared with model group, the rats of sorafenib groups alleviated the volume of rat hind paw and reduced microvessel density. Sorafenib (20, 40mg/kg) groups decreased the percentage of CD4+ T cell and increased the percentage of CD8+ T cell at the same time. All the values were statistically significant (P < 0. 05). Conclusion: Sorafenib can ameliorate adjuvant arthritis in rats, which effect may be related to sorafenib causing CD4+ and CD8+ T cell subset of peripheral blood deviation and reducing microvessel density of synovial tissues.
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AIM To research the therapeutic effects of Hanbi Formula (Astragali Radix,Aconiti Radix cocta,Scorpio,Scolopendrap and Pheretima) on adjuvant-induced arthritis rats (RA) and its mechanism of action.METHODS RA rat models were established by using Freund's adjuvant,and then the rats were divided into six groups,namely control group,model group,dexamethasone positive group,Baoguang Fengshi Liquid (Notopterygii Rhizoma et Radix,Radix angelicae pubescentis,Chuanxiong Rhizoma,etc.) positive group,and low,high doses of Hanbi Formula groups.The volume and swelling of toes were measured.The interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) of serum were detected by ELISA;the proliferative capacity of lymphocytes was tested by methyl thiazolyl tetrazolium (MTI) method;synovial tissue was histopathologically examined with HE staining.Finally,the expressions of interleukin-17 (IL-17) and TNF-α in synovial tissue were determined by immunohistochemical assays.RESULTS Hanbi Formula could significantly relieve toe swelling of RA rats.Compared with the model group,Hanbi Formula could significantly alleviate synovitis in rats with RA,down-regulate the expressins of IL-1 β and TNF-α in serum and synovial tissue,and inhibit lymphocyte proliferation.There were no significant differences in above indices between low-dose and high-dose Hanbi Formula groups,which was quite with Baoguang Fengshi Liquid,but less than dexamethasone.CONCLUSION Hanbi Formula possesses an obvious function of anti-RA,and its mechanism may be related to the inhibition of lymphocyte proliferation and reducing secretion of inflammatory cytokines.
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OBJECTIVE:To study the pharmacokinetics of triptolide in Tripterygium glycosides tablet in normal rats and adju-vant arthritis model rats in vivo,and provide reference for clinical rational drug use. METHODS:12 SD rats were randomly divid-ed into normal group and model group,6 in each group. Model group was subcutaneously injected complete Freund's adjuvant 0.1 mL to induce adjuvant arthritis model,normal group was subcutaneously injected the same volume of saline. After 14 d model-ing,2 groups were given Tripterygium glycosides tablet suspension 96 mg/kg intragastrically,the blood sample of eyes 0.4 mL were respectively taken before and 10,30,45,60,90,120,150,180,240,300,420 min after administration. The plasma con-centration of triptolide was determined by HPLC,the pharmacokinetic parameters were calculated by DAS 2.0 software,and the parameters were compared. RESULTS:The pharmacokinetic parameters of triptolide in normal group were cmax of(1.139±0.114)μg/mL,tmax of(2.167±0.606)h,t1/2α of(5.500±3.610)h,AUC0-7 h of(5.052±0.371)μg·h/mL,MRT0-7 h of(3.224±0.119)h, and CL of(11.616±2.986)mL/h;and those in model group were cmax of(0.916±0.103)μg/mL,tmax of(3.083±0.801)h,t1/2αof(5.593±1.795)h,AUC0-7 h of(4.707±0.347)μg·h/mL,MRT0-7 h of(3.429±0.139)h,and CL of(11.246±2.638) mL/h. Compared with normal group,cmax in model group was significantly decreased,tmax and MRT0-7 h were significantly prolonged(P<0.05). CONCLUSIONS:Adjuvant arthritis can affect the pharmacokinetics of triptolide in rats in vivo,and promote its absorption and removal.