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ObjectiveTo study the clinical efficacy of the Qingre Lishi Huazhuo method on patients with chronic gouty arthritis of dampness-heat obstruction syndrome and the effect on nucleotide-binding oligomerization domain-like receptor 3（NLRP3）/interleukin-1β （IL-1β） signaling pathway to preliminarily explore its mechanism. MethodSixty patients with chronic gouty arthritis of dampness-heat obstruction syndrome were enrolled and divided into a treatment group （30 cases） and a control group （30 cases） according to the random number table method. Thirty people were assigned to the healthy group. Patients in the control group were treated with oral Febuxostat， while those in the treatment group were treated with modified Simiaosan combined with Febuxostat. Treatment lasted four weeks. The general clinical data， traditional Chinese medicine （TCM） syndrome scores， serum uric acid （UA）， serum creatinine （SCr）， blood urea nitrogen （BUN）， fasting blood glucose （FPG）， low-density lipoprotein （LDL）， triglyceride （TG）， total cholesterol （TC）， erythrocyte sedimentation rate （ESR）， and C-reactive protein （CRP） of patients were recorded. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of IL-1β，TNF-α， and IL-6，and the levels of NLRP3，cysteinyl aspartate-specific protease-1 （Caspase-1）， and apoptosis-associated speck-like protein containing a CARD （ASC） were detected by Western blot. ResultBefore treatment， the levels of body mass index （BMI）， systolic blood pressure （SBP），diastolic blood pressure （DBP），UA，SCr，BUN，FPG，LDL，TG，and TC in both groups significantly increased （P<0.05，P<0.01），and the levels of HDL significantly decreased as compared with those in the healthy group（P<0.05）. Additionally， the levels of IL-1β， TNF-α， and IL-6 in both groups significantly increased before treatment （P<0.01）. Compared with the results before treatment， patients in the two groups had significant reductions in tube pain， joint tenderness， joint swelling，joint fever， activity disorders， body fatigue， sliminess， bitter mouth， yellow and red urine， and tongue manifestation scores （P<0.05，P<0.01）. Compared with patients in the control group after treatment， those in the treatment group had a significant decrease in joint fever， body fatigue， sliminess， bitter mouth，sticky stool，yellow and red urine， tongue manifestation score， and pulse score （P<0.05）. The total effective rate in the treatment group was 80.0% （24/30）， higher than 56.7% （17/30）in the control group（χ2=11.916，P<0.05）. Compared with the results before treatment， BMI， SBP， DBP， UA， SCr， BUN， FPG， LDL， TG， TC， ESR，CRP， IL-1β， TNF-α， IL-6 levels， and VAS score in both groups significantly decreased （P<0.05，P<0.01）. Compared with patients in the control group after treatment， those in the treatment group had decreased DBP，ESR， IL-1β levels， and VAS score （P<0.05）. Western blot results showed that before treatment， the protein expression of NLRP3， Caspase-1， and ASC in peripheral blood mononuclear cells （PBMCs） of patients in both groups were higher than those in the healthy group （P<0.01）. Compared with the results before treatment， the protein expression of NLRP3， Caspase-1， and ASC in PBMCs in patients of both groups after treatment decreased （P<0.05，P<0.01）. Compared with the control group after treatment， the treatment group showed decreased expression levels of NLRP3 and Caspase-1（P<0.05）. ConclusionThe Qingre Lishi Huazhuo method can effectively improve the clinical symptoms and reduce inflammation of chronic gouty arthritis of dampness-heat obstruction syndrome with good safety. The mechanism may be related to the inhibition of the NLRP3/IL-1β signaling pathway.
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Objective:To investigate the clinical efficacy of Simiaosan combined with arthroscopic radiofrequency ablation in the treatment of acute traumatic knee synovitis and its effects on inflammatory markers and knee joint function. Method:A total of 92 patients with acute traumatic knee synovitis who were treated in our hospital from February 2017 to November 2018 were randomly divided into observation group and control group, with 46 cases in each group. The patients in observation group were treated with Simiaosan combined with arthroscopic radiofrequency ablation, while the patients in control group were treated radiofrequency ablation combined with Gubi tablet, synovitis granule and imrecoxib tablets. The efficacy in the two groups was observed one month after operation. The degree of pain and the swelling of knee joint were evaluated before and one month after operation, and the function of knee joint was evaluated by lysholm knee score system (LKSS) before and one month after operation. And at the same time, the knee joint activity was measured, erythrocyte sedimentation rate (ESR) was analyzed by Wechsler's method, and hypersensitivity C-reactive protein (hs-CRP) was detected by immunoturbidimetry. The adverse reactions and complications of the two groups were observed. Result:Compared with control group after treatment, the total effective rate in observation group was significantly higher than that in control group, with statistically significant differences (P<0.05). The visual analogue scale (VAS) scores of knee pain in both groups after treatment were significantly lower than those before treatment (P<0.05), while the joint swelling scores were significantly higher (P<0.05). After treatment, the VAS score of knee pain in observation group was significantly lower than that of control group at the same time (P<0.05), while the joint swelling score was significantly higher (P<0.05). After treatment, the LKSS score and the range of motion of the affected knee joints in both groups were significantly increased compared with those before treatment (P<0.05), but with more significant improvement in observation group (P<0.05). The levels of ESR in peripheral blood and hs-CRP in serum of the two groups were significantly lower than those before treatment (P<0.05), especially in observation group (P<0.05). No obvious side effects were observed in observation group during the treatment with Simiaosan. There was no significant difference in the incidence of complications between the two groups. Conclusion:The treatment of Simiaosan combined with radiofrequency ablation under arthroscope has a significant efficacy in the treatment of acute traumatic gonarthromeningitis. The knee joint function of the patients was significantly improved, and the mechanism may be related to the inhibition of inflammatory reaction in vivo.
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Objective::To observe the clinical efficacy of modified Simiaosan on synovitis of knee joint with damp-heat obstruction collateral syndrome and the effect on inflammatory factors and neuropeptide substances in synovial fluid. Method::One hundred and thirty-five patients were randomly divided into control group(67 cases) and observation group(68 cases) by random number table. Patients' intra-articular effusion was drawn out. Triamcinolone acetonide was injected into arthrosis for 2 times, 1 time/week, and aceclofenac sustained-release tablets were given for 4 weeks, 0.2 g/time, 1 time/day. In addition to the therapy of control group, patients in observation group were also given modified Simiaosan for 4 weeks, 1 dose/day. Before and after treatment, pain, swelling of knee joint and were scored, Western Ontario and McMaster University (WOMAC) were adopted for scoring knee score, and damp-heat obstruction syndrome and local signs of knee joint were also assessed. And levels of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), hypersensitive C-reactive protein (hs-CRP), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were detected. Result::After treatment, scores of pain and swelling of knee joint in observation group were lower than those in control group (P<0.01). Scores of WOMAC, the total score, integral of damp-heat obstruction collateral syndrome, knee flexion-extension range score and floating patella test were all lower than those in control group (P<0.01). And levels of IL-1β, IL-6, TNF-α, hs-CRP, SP, CGRP, NPY and VIP were all lower than those in control group (P<0.01). Analyzed by rank sum test, the clinical efficacy in observation group was better than those in control group (Z=2.089, P<0.05). Conclusion::Modified Simiaosan can significantly alleviate pain and swelling symptoms, promote the recovery of knee joint function, and inhibit the expressions of proinflammatory factors and neuropeptides in synovial fluid, with a better clinical efficacy.
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Objective;To explore the mechanism ofSimiaosan drug-containing serum on prevention and treatment of renal fibrosis.Methods Human renal tubular epithelial cells (HK-2) were divided into blank group, model group, control group, and drug-containing serum high dosage group, medium dosage group and low dosage group. The expressions of CTGF and BMP-7 were determined by real-time PCR assay and immunocytochemistry.Results After the HK-2 cell was induced by uric acid (UA), the expression of CTGF significantly increased (P<0.05), the expression of BMP-7 significantly decreased (P<0.05). After intervened bySimiaosan, the expression of CTGF significantly decreased (P<0.05), the expression of BMP-7 significantly increased (P<0.05) and present dosage dependent.Conclusion Reducing the expression of CTGF and up-regulation the expression of BMP-7 and controlling epithelial-myofibroblast transdifferentiation may be the mechanism ofSimiaosan on prevention and treatment of renal fibrosis.
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AIM@#To observe the effect of modified Si-Miao-San (mSMS) on advanced glycation end products (AGEs)-induced pancreatic B cell dysfunction, as well as examining the underlying mechanisms.@*METHOD@#Pancreatic B cells (INS-1) were stimulated with advanced glycation end products (AGEs, 200 μg·mL(-1)) for 24 h to produce dysfunction in pancreatic B cells and the effects of mSMS observed on insulin secretion, NF-κB (p65) phosphorylation, reactive oxygen species (ROS) production, mitochondria membrane potential (Δψm), cell apoptosis, phosphorylation of AMP-kinase (AMPK), and caspase 3 activity.@*RESULTS@#The AGEs challenge resulted in increased basal insulin secretion, but decreased insulin secretion in response to high glucose, whereas this situation was reversed by mSMS treatment. AGEs stimulation induced NF-κB (p65) phosphorylation and reactive oxygen species (ROS) production, as well as Δψm collapse and cell apoptosis. mSMS inhibited ROS production and inhibited NF-κB activation by attenuating p65 phosphorylation. Meanwhile, AGEs-induced Δψm collapse and cell apoptosis were also reversed by mSMS treatment. Compound C, an inhibitor of AMP-Kinase (AMPK), abolished the beneficial effects of mSMS on the regulation of B cell function, indicating the involvement of AMPK.@*CONCLUSION@#mSMS ameliorated AGEs-induced B cell dysfunction by suppressing ROS-associated inflammation, and this action was related to its beneficial regulation of AMPK activity.
Subject(s)
Animals , Humans , Rats , AMP-Activated Protein Kinases , Genetics , Metabolism , Apoptosis , Cell Line, Tumor , Drugs, Chinese Herbal , Pharmacology , Glucose , Metabolism , Glycation End Products, Advanced , Metabolism , Inflammation , Drug Therapy , Genetics , Metabolism , Insulin-Secreting Cells , Cell Biology , Metabolism , Phosphorylation , Reactive Oxygen Species , MetabolismABSTRACT
Modified Si-Miao-San (mSMS) is composed of Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Coptidis Semen Coicis and Atractylodes Rhizome. The prescription is used for the management of diabetes and insulin resistance in the clinic. This study aims to investigate its regulation of glucose disposal in adipocytes. Differentiated 3T3-L1 adipocytes were stimulated with conditioned medium derived from activated macrophages to induce insulin resistance and observed the effects of Mac-CM on insulin-mediated glucose uptake along the insulin receptor substrate-1/PI3K/Akt signaling pathway. Moreover, its regulation of AMPK phosphorylation was also investigated. mSMS enhanced AMPK phosphorylation and promoted basal glucose uptake in adipocytes; mSMS inhibited NF-κB activation by reducing P65 phosphorylation and improved insulin-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to the restoration of insulin-mediated glucose uptake when cells were exposed to inflammatory stimulation. These beneficial effects were diminished in the presence of the AMPK inhibitor compound C. mSMS positively regulated AMPK activity, and this action contributed to improving insulin PI3K signaling by the beneficial regulation of IRS-1 function through inhibition of inflammation in adipocytes.