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OBJECTIVE@#To observe the immediate analgesic effect of electroacupuncture (EA) combined with diclofenac sodium on acute gouty arthritis (AGA).@*METHODS@#A total of 90 patients with AGA were randomly divided into a low-dose medication (LM) group (30 cases, 1 case was eliminated, 1 case dropped off), a conventional medication (CM) group (30 cases, 1 case dropped off) and a combination of acupuncture and medication (AM) group (30 cases ). The LM group was given oral administration of 50 mg diclofenac sodium sustained-release capsule; the CM group was given oral administration of 100 mg diclofenac sodium sustained-release capsule; on the basis of the treatment of LM group, the AM group was treated with electroacupuncture at ashi points, Dadu (SP 2), Taichong (LR 3), Taibai (SP 3), Neiting (ST 44), Sanyinjiao (SP 6), Zusanli (ST 36) and Yinlingquan (SP 9) on the affected side, and Taichong (LR 3) and Zusanli (ST 36), Sanyinjiao (SP 6) and Yinlingquan (SP 9) were connected to electroacupuncture respectively, continuous wave, 2 Hz in frequency. The visual analogue scale (VAS) scores of pain before treatment and after 10 min, 2 h, 4 h and 6 h of treatment completion, joint tenderness and swelling scores before treatment and after 10 min and 6 h of treatment completion were compared, and the rate of diclofenac sodium addition within 24 h after treatment completion was recorded among the three groups.@*RESULTS@#After 10 min of treatment completion, the scores of VAS, joint tenderness and joint swelling in the AM group were lower than those before treatment (P<0.05), and the VAS score in the AM group was lower than that in the other two groups (P<0.05). After 2, 4 and 6 h of treatment completion, the VAS scores of the three groups were lower than those before treatment (P<0.05), and the scores in the AM group were lower than those in the LM group (P<0.05). After 6 h of treatment completion, the joint tenderness scores of the three groups and the joint swelling scores of the AM group and the CM group were lower than those before treatment (P<0.05), and the joint tenderness and swelling scores of the AM group were lower than those of the LM group (P<0.05). The rate of diclofenac sodium addition was 3.3 % (1/30) and 3.4 % (1/29) in the AM group and the CM group, respectively, which were lower than 17.9% (5/28) in the LM group (P<0.05).@*CONCLUSION@#Electroacupuncture combined with diclofenac sodium have a good immediate analgesic effect in the treatment of AGA, and have the advantages of small dosage of analgesic drugs and less adverse reactions.
Subject(s)
Humans , Diclofenac , Electroacupuncture , Arthritis, Gouty/drug therapy , Delayed-Action Preparations , Acupuncture Therapy , ArthralgiaABSTRACT
ObjectiveTo observe the effect of Huanglian Jiedutang on the inflammatory injury in the mouse model of acute gouty arthritis （AGA） and to explore the mechanism of Huanglian Jiedutang in treating AGA. MethodForty male C57BL/6J mice were randomized into blank， model， colchicine （0.83 mg·kg-1）， and Huanglian Jiedutang （5 g·kg-1） groups. The mouse model of AGA was established by injecting monosodium urate （MSU） crystals into the ankle joint. The swelling degree of the right ankle joint of each mouse was measured every day for 7 days， and the pathological changes of the ankle joint were detected by hematoxylin-eosin （HE） staining after 7 days. The other 40 C57BL/6J mice were grouped as above. After 18 hours of modeling， the right ankle joint was collected， and real-time polymerase chain reaction was employed to measure the mRNA levels of interleukin （IL）-1β， tumor necrosis factor （TNF）-α， IL-6， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and Caspase-1. The expression levels of IL-1β， TNF-α， and IL-6 were measured by the enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of NLRP3 inflammasome， Toll-like receptor 4 （TLR4）， and nuclear factor-κB （NF-κB）. ResultCompared with the blank group， the model group showed swelling right ankle joint （P<0.01）， obvious foreign body granuloma in the ankle joint with inflammatory cell infiltration. After the treatment with Huanglian Jiedutang， the ankle joint swelling was relieved （P<0.05， P<0.01）， and the size of foreign body granuloma was reduced. Compared with the blank group， the model group showed up-regulated mRNA levels of IL-1β， TNF-α， and IL-6 in the ankle joint tissue （P<0.01）， up-regulated mRNA levels of NLRP3 and Caspase-1 in the NLRP3 inflammasome （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， Caspase-1， TLR4， and NF-κB （P<0.05， P<0.01）. Huanglian Jiedutang down-regulated the mRNA levels of IL-1β， TNF-α， IL-6， NLRP3， and Caspase-1 （P<0.05， P<0.01） and the protein levels of IL-1β， TNF-α， IL-6， NLRP3， Caspase-1， TLR4， and NF-κB （P<0.05 or P<0.01）. ConclusionInjecting MSU crystal resulted in local inflammatory injury of the joints in the mouse model of AGA. The treatment with Huanglian Jiedutang may alleviate the inflammatory injury by regulating the NLRP3 inflammasome and TLR4/NF-κB signaling pathway.
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ObjectiveTo investigate the therapeutic effect of Qingmei compound on acute gouty arthritis （AGA） in rats and preliminarily clarify its mechanism. MethodForty male SD rats were randomly divided into a blank group， a model group， a colchicine group （0.3 mg·kg-1）， and low- and high-dose Qingmei compound groups （200 and 400 mg·kg-1）， with eight rats in each group. The AGA model was induced by injecting 50 g·L-1 monosodium urate （MSU） into the ankle joint of the rats except those in the blank group. The ankle swelling index was measured before and 6， 24， and 48 h after modeling. The pathological changes in the joint tissues of AGA rats were observed by hematoxylin-eosin （HE） staining. The expression of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the joint tissues of rats was detected by immunohistochemistry. The protein expression of NOD-like receptor protein 3 （NLRP3） pathway and key proteins in the joint tissues of rats was detected by Western blot. ResultCompared with the blank group， the model group showed increased ankle swelling index， synovial hyperplasia， and inflammatory infiltration， and up-regulated expression of IL-1β， TNF-α， and NLRP3 proteins in the ankle joint and the ratio of Caspase-1 shear body to Caspase-1 precursor protein （Caspase-1 p20/Caspase-1） （P<0.01）. Compared with the model group， the Qingmei compound groups showed reduced ankle swelling index of AGA rats， especially the low-dose Qingmei compound group （P<0.01）. Meanwhile， Qingmei compound inhibited synovial hyperplasia and inflammatory infiltration （P<0.01） and reduced the levels of IL-1β， TNF-α， and NLRP3 proteins and Caspase-1 p20/Caspase-1 in joint tissues （P<0.01）. ConclusionQingmei Compound can significantly alleviate the joint swelling and inflammatory infiltration of AGA， and its mechanism may be related to the inhibition of the NLRP3 signaling pathway.
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ObjectiveTo investigate the therapeutic effect of Qingmei compound on acute gouty arthritis （AGA） in rats and preliminarily clarify its mechanism. MethodForty male SD rats were randomly divided into a blank group， a model group， a colchicine group （0.3 mg·kg-1）， and low- and high-dose Qingmei compound groups （200 and 400 mg·kg-1）， with eight rats in each group. The AGA model was induced by injecting 50 g·L-1 monosodium urate （MSU） into the ankle joint of the rats except those in the blank group. The ankle swelling index was measured before and 6， 24， and 48 h after modeling. The pathological changes in the joint tissues of AGA rats were observed by hematoxylin-eosin （HE） staining. The expression of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the joint tissues of rats was detected by immunohistochemistry. The protein expression of NOD-like receptor protein 3 （NLRP3） pathway and key proteins in the joint tissues of rats was detected by Western blot. ResultCompared with the blank group， the model group showed increased ankle swelling index， synovial hyperplasia， and inflammatory infiltration， and up-regulated expression of IL-1β， TNF-α， and NLRP3 proteins in the ankle joint and the ratio of Caspase-1 shear body to Caspase-1 precursor protein （Caspase-1 p20/Caspase-1） （P<0.01）. Compared with the model group， the Qingmei compound groups showed reduced ankle swelling index of AGA rats， especially the low-dose Qingmei compound group （P<0.01）. Meanwhile， Qingmei compound inhibited synovial hyperplasia and inflammatory infiltration （P<0.01） and reduced the levels of IL-1β， TNF-α， and NLRP3 proteins and Caspase-1 p20/Caspase-1 in joint tissues （P<0.01）. ConclusionQingmei Compound can significantly alleviate the joint swelling and inflammatory infiltration of AGA， and its mechanism may be related to the inhibition of the NLRP3 signaling pathway.
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Based on network pharmacology, the mechanism of Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus(PL) combination against acute gouty arthritis(AGA) was explored and preliminarily verified by animal experiment. The chemical components and corresponding targets of PL were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The active components with oral bioavailability(OB)≥30% and drug-likeness(DL)≥0.18 were screened based on literature, and the related protein targets were collected. Then the protein targets were standardized with the help of UniProt database. The AGA-related targets were searched from GeneCards, NCBI, and DrugBank. The common targets of the disease and the medicinals were yielded by FunRich V3, and the protein-protein interaction(PPI) network was constructed to screen the key targets, followed by Gene Ontology(GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the key targets. Afterwards, some of the key targets were verified by sodium urate crystal-induced AGA mouse model. A total of 25 active components and 287 targets of PL, 811 targets of AGA, and 88 common targets were screened out. PPI network analysis showed that tumor necrosis factor(TNF), interleukin-6(IL-6), and interleukin-1β(IL-1β) may be the core targets of PL in the treatment of AGA. The key targets were mainly involved in 566 GO terms(P<0.05), including multiple biological processes such as inflammatory response and immune response. Moreover, they were related to 116 KEGG pathways and these pathways were involved in inflammation and immunity, mainly including NOD-like receptor signaling pathway and TNF signaling pathway. Animal experiment confirmed that PL can alleviate ankle swelling, improve abnormal gait, and down-regulate the protein expression of TNF-α, IL-6, and IL-1β in AGA mice, indicating that PL can treat AGA through TNF-α, IL-6, and IL-1β and the feasibility of network pharmacology to predict drug targets. This study preliminarily discussed the key targets and biological signaling pathways involved in the treatment of AGA with PL combination, which reflected the multi-pathway and multi-target action characteristics of Chinese medicine. Moreover, this study laid a scientific basis for research on the treatment of AGA with PL combination, as well as the mechanism of action.
Subject(s)
Animals , Mice , Arthritis, Gouty/drug therapy , Drugs, Chinese Herbal/therapeutic use , Ligustrum , Network Pharmacology , RhizomeABSTRACT
Objective:Sodium urate was used to induce acute gouty arthritis rat model, and to observe the inflammatory response of rats and the intervention effect of diclofenac sodium on the expression of Toll-like receptor-related (TLR) protein of ankle joint.Methods:Thirty males specific pathogen free (SPF) grade Wistar rats were used to develop the models. Random number table method was used to divide the rats into normal saline control group, model group, and drug group (diclofenac sodium t 1.35 mg/g body weight), 10 rats in each group. After fully grinding the sodium urate crystals, an appropriate amount of saline and Tween-80 (9∶1) was added to make a suspension, and the sodium urate crystals (25 mg/ml) were injected to the right posterior ankle of the rats in the model and drug groups. The solution was 0.2 ml, and rats in the sham group were injected with 0.2 ml of normal saline at the same location. After the model was established, drug and equal volume of purified water were administrated intragastrically once a day for 7 days. The toe volume device was used to measure the joint swelling of the rat (at 4 h, 8 h, 24 h, 48 h, 72 h) , and blood was taken from the abdominal aorta after anesthesia to determine the rat kidney function, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) content, the rat ankle joint TLR4, myeloid differentiation factor (MyD88), NF-κBp65 protein expression were determined using Western blot and immunohistochemical methods. Multiple comparisons were carried out using single factor analysis of variance (ANOVA), comparing the two groups by using LSD- t, the comparison of different times using repetitive measure analysis of variance (repeated measures). Results:After the models were established, the rat's right ankle joint showed various degrees of redness, slow walking, and unresponsiveness. Compared with the normal saline control group, under the light microscope, the ankle synovial cells of the model group proliferated, with localized degeneration and necrosis, and many inflammatory cell infiltration. The rat serum inflammatory factors IL-1β, IL-6, TNF-α in the diclofenac sodium group [(24.6±3.3) pg/ml, (151±21) pg/ml, (61±16) pg/ml] were significantly reduce compared with model group [(28.4±4.3) pg/ml, (173±26) pg/ml, (81±5) pg/ml] ( t=2.296, P<0.01; t=2.909, P<0.01; t=2.352, P<0.01). Compared with normal saline group, variance analysis showed that the NF-κBp65, MyD88, TLR4 protein expression of ankle joint detected by Western bolt method and immunohistochemistry method was significantly increased in the model group. Compared with the model group, diclofenac sodium the ankle tissue protein expression of NF-κBp65, MyD88, and TLR4 was significantly inhibited. There were statistical significances in three groups ( P<0.05 or P<0.001). Conclusion:The level of inflammatory factors in acute gout arthritis rats model induced by sodium urate crystals is increased, and the expression of TLR4/MyD88/NF-КBp65 proteins in ankle joint tissue is increased, which affects the TLR signaling pathway. Diclofenic has inhibitory and relieving effects.
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OBJECTIVE@#To detect the differentially expressed inflammatory proteins in acute gouty arthritis (AGA) with protein chip.@*METHODS@#The Raybiotech cytokine antibody chip was used to screen the proteomic expression in serum samples of 10 AGA patients and 10 healthy individuals. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were applied to determine the biological function annotation of differentially expressed proteins and the enrichment of signal pathways. ELISA method was used to verify the differential protein expression in 60 AGA patients and 60 healthy subjects. The ROC curve was employed to evaluate the diagnostic value of differential proteins in AGA patients.@*RESULTS@#According to|log@*CONCLUSIONS@#Proteomics can be applied to identify the biomarkers of AGA, which may be used for risk prediction and diagnosis of AGA patients.
Subject(s)
Humans , Arthritis, Gouty/diagnosis , Cytokines/genetics , Gene Expression Profiling , Gene Expression Regulation , Inflammation , Protein Array Analysis , ProteomicsABSTRACT
Objective::To observe the clinical effect of addition and subtraction therapy of Yiyiren Tang with external application therapy in the patients with acute gouty arthritis (AGA) and damp-heat obstruction syndrome, and to investigate its effect on inflammatory factors. Method::One hundred and fifty-three patients were randomly divided into control group (77 cases) and observation group (76 cases) by random number table. Patients in control group got meloxicam tablets after the meal, 1 tablet/day, 1 time/day, diclofenac sodium gel, 3 times/days. On the basis of meloxicam tablets, patients in observation group additionally received addition and subtraction therapy of Yiyiren Tang by oral and topical applications. The course of treatment was 7 days in both groups. Scores of visual analogue score of pain (VAS) were graded everyday, and the relief time and disappearance time of pain were recorded. Before and after treatment, scores of damp-heat obstruction syndrome were recorded. Levels of uric acid (UA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), serum cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6-keto-prostatic factor F1alpha (6-keto-PGF1α) were all detected, and the safety was evaluated. Result::The clinical efficacy in observation group was better than that in control group (Z=2.205, P<0.05). The relief time and disappearance time of pain were shorter than those in control group (P<0.01). At the 1st, 3rd, 5th and 7th day after treatment, scores of VAS were lower than those in control group (P<0.01). After treatment, the scores of main symptoms such as joint pain, tenderness, swelling and dyskinesia, scores of the secondary symptoms and the total scores of damp-heat obstruction syndrome were all lower than those in control group (P<0.01). After treatment, levels of ESR, CRP, UA, IL-1β, IL-6, IL-8, TNF-α, COX-2, PGE2 and TXB2 were all lower than those in control group (P<0.01). Conclusion::Based on the treatment of meloxicam, addition and subtraction therapy of Yiyiren Tang by oral and topical administration methods can quickly relieve and eliminate pain, alleviate the main clinical symptoms and inhibit inflammation in patients with damp-heat obstruction syndrome, showing good clinical efficacy and safety.
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Objective::To explore the effect of Dioscoreae Nipponicae Rhizoma extract (DNRe) on rats with acute gouty arthritis (AGA) based on urine metabolomics and to search for the related potential biomarkers and metabolic pathways. Method::Rat model of AGA induced by monosodium urate (MSU) was selected, 40 rats were randomly divided into the blank group (k), the DNRe group (g), the model group (m), and the DNRe treatment group (gm), with 10 rats in each group. The drug-administered group was administered with DNRe at a dose of 0.48 g·kg-1 once a day for 5 days. The urine was gathered after the last administration, and analyzed with UPLC-Q-TOF/MS coupled with pattern recognition techniques, electrospray ionization (ESI) under positive and negative ion scanning mode was adopted, data collection range was m/z 100-1 500 with full scanning mode. Result::A total of 12 common potential biomarkers were identified as sarcosine, dimethylglycine, deoxycytidine, uric acid, 5-hydroxytryptamine (5-HT), L-cystathionine, 4-pyridoxic acid, deoxyuridine, melatonin, 5-methoxytryptamine, fumaric acid and cytidine. Compared with the blank group, the 12 potential biomarkers in the DNRe group were significantly down-regulated. Compare with the model group, 10 metabolites were up-regulated and 2 metabolites were down-regulated in the 12 potential biomarkers of the DNRe treatment group, the abnormal expression of 10 markers including sarcosine, uric acid, L-cystathionine, 4-pyridoxic acid, deoxyuridine, 5-methoxytryptamine, cytidine, dimethylglycine, melatonin, fumaric acid could be modulated by DNRe. The strongest metabolic pathways associated with AGA were cysteine and methionine metabolism, and tryptophan metabolism. Conclusion::The effect of DNRe on AGA may be related to the promotion of conversion level from cystathionine to cysteine in the cysteine and methionine metabolism, and the up-regulating melatonin level in tryptophan metabolism.
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Objective:To observe the clinical efficacy of modified Danggui Niantongtang combined with Xuanbitang in treating damp-heat type acute gouty arthritis, and investigate its effect on levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α). Method:Totally 126 patients were randomly divided into control group and observation group, with 63 cases in each group. In addition to non-medication treatment, patients in control group were given conventional western medicine treatment for 1 week, while patients in observation group were given modified Danggui Niantongtang combined with Xuanbitang for 1 week. The levels of IL-1β，IL-6，IL-8，TNF-α before and after treatment were observed. Result:The total effective rate was 79.37% in control group and 95.24% in observation group, with significant differences (P<0.05). After treatment, the scores of arthralgia, tenderness, swelling, activity restriction in both groups were significantly decreased (P<0.01), and those in observation group were lower than those in control group (P<0.05). The levels of uric acid (UA), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) were significantly decreased (P<0.01) after treatment, and those in observation group were lower than those in the control group (P<0.05). The levels of IL-1β，IL-6，IL-8，TNF-α were significantly decreased (P<0.01) after treatment, and those in the observation group were lower than those in the control group (P<0.05). Conclusion:Compared with conventional western medicine treatment, modified Danggui Niantongtang combined with Xuanbitang has a better efficacy in treating damp-heat type acute gouty arthritis and reducing levels of IL-1β，IL-6，IL-8，TNF-α.
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Objective:To observe the clinical efficacy of modified Bixie Shengshitang on acute gouty arthritis due to hot and humid syndrome. Method:According to the random number table method， 130 cases were randomly divided into control group and observation group， with 65 cases in each group. All of the cases were given the basic non-drug therapy. The control group was given colchicine， while observation group was given modified Bixie Shengshitang + colchicine for 14 d. Before treatment and at 3， 7 and 14 d after treatment， total symptom score （TSS） and traditional Chinese medicine （TCM） syndrome were observed between the two groups， respectively. Blood uric acid （BUA）， urinary uric acid （UUA）， erythrocyte sedimentation rate （ESR）， proinflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin-1 （IL-1）， interleukin-8 （IL-8）］ and anti-inflammatory factors ［interforon gamma receptor （IFN-γ）， interleukin-4 （IL-4）， interleukin-18（IL-18）］ in serum and joint fluid were detected before and after treatment. The clinical efficacy and safety of the two groups were compared. Result:The total effective rate was 96.9% （62/64） in observation group， which was higher than 80.6% （50/62） in control group （χ2=5.713， P<0.05）. Compared with control group at 3， 7 and 14 d after treatment， TSS and TCM syndrome scores in observation group were significantly reduced （P<0.05）. Compared with control group after treatment， BUA， ESR， TNF-α， IL-1β， IL-8 and UUA， IFN-γ， IL-4 and IL-18 were significantly decreased in observation group （P<0.05）. There was no serious adverse event during the study period. The incidence of adverse reactions was 54.7% （35/64） in observation group， which was lower than 82.3% （51/62） in control group （χ2=9.326， P<0.05）. Conclusion:Modified Bixie Shengshitang can significantly alleviate the clinical symptoms of patients with acute gouty arthritis due to hot and humid syndrome， and adjust levels of uric acid and inflammatory cytokines， with a low recurrence rate.
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The aim of this paper was to study the effect and mechanism of alcohol extract from Polygonum cuspidatum(PCE) on acute gouty arthritis in C57 BL/6 mice through NLRP3/ASC/caspase-1 axis. The model mice which injected with ankle joint injection of sodium urate crystals(MSU) were orally administrated with three different concentration of PCE, with colchicine as positive control. HE staining was used for observing the morphological changes of synovial tissue; concentration of IL-1β, IL-6 and TNF-α secreted by synovial tissue of the ankle joint were detected by ELISA; mRNA and protein expression of NLRP3, ASC and caspase-1 in synovial tissue were detected by RT-PCR and Western blot respectively. The results showed that the swelling degree of ankle joint in model mice were significantly elevated; expression of IL-1β, IL-6 and TNF-α were significantly increased; mRNA and protein expression of NLRP3, ASC and caspase-1 also significant increase, compared with normal control group. The swelling degree of ankle joint significantly relief; expression of IL-1β, IL-6 and TNF-α in joint synovium significantly decrease; mRNA and protein expression of NLRP3, ASC and caspase-1 were significantly decrease in PCE treatment group compared with model group. Our research implied that alcohol extract from P. cuspidatum had positive effect on acute gouty arthritis in mice, and the regulation of NLRP3/ASC/caspase-1 axis may be its mechanism.
Subject(s)
Animals , Mice , Ankle Joint , Arthritis, Gouty , Drug Therapy , CARD Signaling Adaptor Proteins , Metabolism , Caspase 1 , Metabolism , Fallopia japonica , Chemistry , Interleukin-1beta , Metabolism , Interleukin-6 , Metabolism , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein , Metabolism , Plant Extracts , Pharmacology , Tumor Necrosis Factor-alpha , Metabolism , Uric AcidABSTRACT
OBJECTIVE: To explore the effect of electroacupuncture (EA) on the expression of synovial AMP-activated protein kinase (AMPK) protein α， arginase-1 mRNA, nitric oxide synthase 2 (NOS 2) mRNA, NOD-like receptor protein 3 (NLRP 3) mRNA, and interleukin-1 β (IL-1 β) mRNA in acute gouty arthritis (AGA) rats, so as to explore its mechanisms underlying improvement of AGA via M 1/M 2 macrophage polarization. METHODS: Male Wistar rats were randomly divided into normal control, model, medication (colchicine) and EA groups (n＝15 rats in each group). The AGA model was established by injection of sodium urate crystal (MSU) suspension (0.2 mL) into the articular cavity of the left knee. The rats of the normal control group received articular injection of normal saline (0.2 mL) of the left knee, and those of the medication group were treated by gavage of the colchicine (0.3 mg•kg－1•d－1) once daily for 7 days. EA (2 Hz/10 Hz, 1.0 mA) was applied to "Zusanli"(ST 36) and "Sanyinjiao" (SP 6) of the left hind limb for 10 min, once daily for 7 days. The inflammatory conditions of the synovial membrane tissue of the left knee joint were observed by H．E. staining. The expression levels of phosphorylated AMPKα (p-AMPKα) protein, and arginase-1 (a maker of M 2 macrophages) mRNA, NOS 2 (a maker of M 1 macrophages) mRNA, NLRP 3 mRNA, and IL-1 β mRNA in the knee joint synovial tissue were detected by Western blot and quantitative real-time PCR, respectively. RESULTS: Compared with the normal group, the inflammatory cell infiltration of the synovial tissue was more severe, the expression of p-AMPKα protein was significantly decreased (P0.05), except higher up-regulation of arginase-1 mRNA in the medication group (P<0.05)．. CONCLUSION: EA intervention can up-regulate the expression of arginase-1 mRNA and p-AMPKα protein, and down-regulate the expression of NOS 2, IL-1 β and NLRP 3 mRNAs in synovial tissues in AGA rats, which may contribute to its anti-inflammatory effect by promoting conversion of macrophages from M 1 pro-inflammatory phenotype to M 2 anti-inflammatory phenotype.
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Aim Toinvestigatetheeffectsoftotalsap-onin of Dioscorea (TSD)on rats with monosodium u-rate crystal-induced acute gouty arthritis (AGA)and mechanisms.Methods Totally72Wistarratswere randomly devided into six groups,Each group was giv-en corresponding drug before,then rat acute gouty ar-thritis model was made by injection of monosodium u-rate in the ankle joint cavity.The gait,articular swell-ing degree and physiological changes of rats were ob-served.The concentration of TNF-α,IL-1β,IL-18 in serum were detected by ELISA.The levels of pro-IL-1β, NALP3, ASC, pro-caspase-1, and cleaved caspase-1 were detected by Western blot.Results AllTSDgroupsandcolchicinesignificantlychangedthe gait of rats and TSD high and middle groups signifi-cantly reduced joint swelling and diminished the patho-logical changes.The levels of TNF-α,IL-1β,IL-18 in serum were significantly decreased,and the levels of pro-IL-1β,NALP3,ASC,pro-caspase-1 and cleaved caspase-1 were apparently reduced in TSD high and middlegroups.Conclusion TSDpossessesanti-goutfunction and the mechanism may be related to sup-pressing the NALP3 inflammasome activation and in-hibiting the cytokine production.
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Objective To establish a model of acute gouty arthritis( AGA) in rats and observe its maintenance time. Methods The AGA model of rats was established by injecting monosodium urate ( MSU) at the concentration of 25 mg/mL into the ankle joint cavity. The rats were observed for 8 d at different time points. Skin temperature, degree of joint swelling, gait, inflammatory cells in synovial fluid, histopathological changes of synovial tissue and other indicators were observed to determine whether the modeling and maintenance time were successful. Results At 3 h after modeling, differ-ences in the swelling of ankle joint, increase of skin temperature, abnormal gait, the number of inflammatory cells in syno-vial fluid, synovial hyperplasia, capillary congestion, and disarrangement of synovial cells in the rats were observed in the saline group and the model group (P <0. 01). At 4 hours after modeling, the above mentioned inflammatory changes in the saline group were significantly reduced, compared with that at 3 h, showing a significant difference (P<0. 01), while the inflammatory changes of the model group were increased significantly compared with that at 3 hours ( P<0. 01 ) , and showed significant difference compared with the saline group (P<0. 01). At 24 h after modeling, the indexes in the rats of saline group returned to normal, but the inflammation of the model group was increased. At 48-72 h after modeling, the local inflammation such as ankle swelling, skin temperature, and abnormal gait of the rats in the model group reached a peak. The inflammation of the ankle joint in the model group was gradually reduced from 96 to 168 h after the model was established, but there were still significant differences in the indexes compared with the blank group (P<0. 01). At 192 h after modeling, the joint swelling, skin temperature and abnormal gait of the rats in the model group returned to normal, however, there were significant differences in the number of inflammatory cells and the pathological changes of synovial membrane compared with the blank group ( P<0. 01 ) . Conclusions A rat model of AGA can be successfully prepared and identified at 4 h after modeling by injection of MSU crystal suspension into the ankle joint cavity. This rat model of AGA can be maintained at least 168 hours after modeling.
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Objective To study the effect of psychological intervention combined with Votalin emulgel and dexamethasone sticking on the treatment of acute gouty arthritis. Methods 100 patients with acute gouty arthritis treated in our hospital from March 2015 to May 2016 were selected as the research object. They were randomly divided into the control group and the experimental group, with 50 patients in each group. The control group was treated with conventional therapy, the experimental group was treated with psychological intervention combined with Votalin emulgel and dexamethasone sticking, pay attention to the psychological status of patients, strengthen communication and exchanges with patients, the patient's confidence and treatment compliance. The therapeutic effects of the experimental group and the control group were compared and analyzed. Results After the corresponding treatment, the effective rate of the experimental group was 94.0%, which was significantly higher than that of the control group (80.0%), the difference was statistically significant (P<0.05). The remission time of gout in the control group was (12.19±1.56) days,significantly longer than that in the experimental group (9.34±1.21) days, the difference was statistically significant (P<0.05). Conclusion The clinical effect of paste dressing in the treatment of acute gouty arthritis with good psychological intervention combined with Votalin emulgel, dexamethasone, relieve the clinical symptoms of patients with gout, has clinical significance.
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Objective To establish a model of acute gouty arthritis( AGA) in rats and observe its maintenance time. Methods The AGA model of rats was established by injecting monosodium urate ( MSU) at the concentration of 25 mg/mL into the ankle joint cavity. The rats were observed for 8 d at different time points. Skin temperature, degree of joint swelling, gait, inflammatory cells in synovial fluid, histopathological changes of synovial tissue and other indicators were observed to determine whether the modeling and maintenance time were successful. Results At 3 h after modeling, differ-ences in the swelling of ankle joint, increase of skin temperature, abnormal gait, the number of inflammatory cells in syno-vial fluid, synovial hyperplasia, capillary congestion, and disarrangement of synovial cells in the rats were observed in the saline group and the model group (P <0. 01). At 4 hours after modeling, the above mentioned inflammatory changes in the saline group were significantly reduced, compared with that at 3 h, showing a significant difference (P<0. 01), while the inflammatory changes of the model group were increased significantly compared with that at 3 hours ( P<0. 01 ) , and showed significant difference compared with the saline group (P<0. 01). At 24 h after modeling, the indexes in the rats of saline group returned to normal, but the inflammation of the model group was increased. At 48-72 h after modeling, the local inflammation such as ankle swelling, skin temperature, and abnormal gait of the rats in the model group reached a peak. The inflammation of the ankle joint in the model group was gradually reduced from 96 to 168 h after the model was established, but there were still significant differences in the indexes compared with the blank group (P<0. 01). At 192 h after modeling, the joint swelling, skin temperature and abnormal gait of the rats in the model group returned to normal, however, there were significant differences in the number of inflammatory cells and the pathological changes of synovial membrane compared with the blank group ( P<0. 01 ) . Conclusions A rat model of AGA can be successfully prepared and identified at 4 h after modeling by injection of MSU crystal suspension into the ankle joint cavity. This rat model of AGA can be maintained at least 168 hours after modeling.
ABSTRACT
Objective To study the effect of psychological intervention combined with Votalin emulgel and dexamethasone sticking on the treatment of acute gouty arthritis. Methods 100 patients with acute gouty arthritis treated in our hospital from March 2015 to May 2016 were selected as the research object. They were randomly divided into the control group and the experimental group, with 50 patients in each group. The control group was treated with conventional therapy, the experimental group was treated with psychological intervention combined with Votalin emulgel and dexamethasone sticking, pay attention to the psychological status of patients, strengthen communication and exchanges with patients, the patient's confidence and treatment compliance. The therapeutic effects of the experimental group and the control group were compared and analyzed. Results After the corresponding treatment, the effective rate of the experimental group was 94.0%, which was significantly higher than that of the control group (80.0%), the difference was statistically significant (P<0.05). The remission time of gout in the control group was (12.19±1.56) days,significantly longer than that in the experimental group (9.34±1.21) days, the difference was statistically significant (P<0.05). Conclusion The clinical effect of paste dressing in the treatment of acute gouty arthritis with good psychological intervention combined with Votalin emulgel, dexamethasone, relieve the clinical symptoms of patients with gout, has clinical significance.
ABSTRACT
To explore the prevention and protection effect of Diosocorea nipponica (DNM)) on acute gouty arthritis (AGA) rats based on liver metabonomics, and find potential biomarkers and related pathways. AGA model rats were induced by monosodium urate crystal suspension. UPLC-TOF-MS coupled with pattern recognition technique was employed to find out the potential biomarkers and related metabolic pathways. Eleven common potential biomarkers were identified. Among the potential intervention targets in normal rats given by DNM, 4 biomarkers were up-regulated, and the other 4 targets were down regulated. Among the potential intervention targets in AGA rats given by DNM, 5 metabolites were up-regulated by MSU and 5 metabolites were down regulated. The abnormal expression levels of adenosine monophosphate, 5-methyltetrahydrofolic acid, oxidized glutathione, hypoxanthine, docosahexaenoic acid, glutathione, uridine diphosphate glucose and inosine could be corrected by DNM extract. Three pathways were founded with greatest correlation, including purine metabolism, starch and sucrose metabolism and glutathione metabolism. Therefore, it could be inferred that D. nipponica has the effect for anti-acute gouty arthritis by intervening endogenous metabolites from the liver under physiological condition and acute gouty arthritis condition.
ABSTRACT
PURPOSE: Patients with gout are similar to those with bacterial infection in terms of the nature of inflammation. Herein we compared the differences in procalcitonin (PCT) levels between these two inflammatory conditions and evaluated the ability of serum PCT to function as a clinical marker for differential diagnosis between acute gouty attack and bacterial infection. MATERIALS AND METHODS: Serum samples were obtained from 67 patients with acute gouty arthritis and 90 age-matched patients with bacterial infection. Serum PCT levels were measured with an enzyme-linked fluorescent assay. RESULTS: Serum PCT levels in patients with acute gouty arthritis were significantly lower than those in patients with bacterial infection (0.096±0.105 ng/mL vs. 4.94±13.763 ng/mL, p=0.001). However, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels showed no significant differences between the two groups. To assess the ability of PCT to discriminate between acute gouty arthritis and bacterial infection, the areas under the curves (AUCs) of serum PCT, uric acid, and CRP were 0.857 [95% confidence interval (CI), 0.798-0.917, p<0.001], 0.808 (95% CI, 0.738-0.878, p<0.001), and 0.638 (95% CI, 0.544-0.731, p=0.005), respectively. There were no significant differences in ESR and white blood cell counts between these two conditions. With a cut-off value of 0.095 ng/mL, the sums of sensitivity and specificity of PCT were the highest (81.0% and 80.6%, respectively). CONCLUSION: Serum PCT levels were significantly lower in patients with acute gouty attack than in patients with bacterial infection. Thus, serum PCT can be used as a useful serologic marker to differentiate between acute gouty arthritis and bacterial infections.