1.Regulation of Signaling Pathways Related to Myocardial Infarction by Traditional Chinese Medicine: A Review
Wenjun WU ; Chidao ZHANG ; Jingjing WEI ; Xue LI ; Bin LI ; Xinlu WANG ; Mingjun ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):321-330
The pathological changes of myocardial infarction (MI) are mainly characterized by progressive myocardial ischemic necrosis, decline in cardiac diastolic function, thinning of the ventricular wall, and enlargement of the ventricles. The clinical manifestations include myocardial ischemia, heart failure, arrhythmia, shock, and even sudden cardiac death, rendering MI one of the most perilous cardiovascular diseases. Currently, the clinical treatment for MI primarily involves interventional procedures and drug therapy. However, due to their significant side effects and high complication rates associated with these treatments, they fail to ensure a satisfactory quality of life and long-term prognosis for patients. On the other hand, traditional Chinese medicine has demonstrated remarkable potential in improving patient prognosis while reducing side effects. Research has elucidated that various signaling pathways such as nuclear transcription factor-κB (NF-κB), adenosine 5̒-monophosphate-activated protein kinase (AMPK), transforming growth factor-β (TGF-β)/Smads, mitogen-activated protein kinase (MAPK), Wnt/β-catenin (β-catenin), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt) play crucial roles in regulating the occurrence and development of MI. Effectively modulating these signaling pathways through its therapeutic interventions, traditional Chinese medicine can enhance MI management by inhibiting apoptosis, providing anti-inflammatory properties, alleviating oxidative stress levels, and resisting myocardial ischemia. Due to its notable efficacy and favorable safety, it has become an area of focus in clinical practice.
2.Construction and Application Evaluation of an Integrated Traditional Chinese and Western Medicine Risk Prediction Model for Readmission in Patients with Stable Angina of Coronary Heart Disease:A Prospective Study Based on Real-World Clinical Data
Wenjie HAN ; Mingjun ZHU ; Xinlu WANG ; Rui YU ; Guangcao PENG ; Qifei ZHAO ; Jianru WANG ; Shanshan NIE ; Yongxia WANG ; Jingjing WEI
Journal of Traditional Chinese Medicine 2025;66(6):604-611
ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease (CHD) based on real-world clinical data, to establish a risk prediction model of integrated traditional Chinese and western medicine, in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD, who were divided into a training set and a validation set at a 7∶3 ratio. General information, traditional Chinese medicine (TCM)-related data, and laboratory test results were uniformly collected. After a one-year follow-up, patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination, calibration, and clinical decision curve analysis. ResultsA total of 682 patients were included, with 477 in the training set and 205 in the validation set, among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history [OR = 6.93, 95% CI (1.58, 30.45)], wiry pulse [OR = 2.58, 95% CI (1.42, 4.72)], weak pulse [OR = 3.97, 95% CI (2.06, 7.67)], teeth-marked tongue [OR = 4.38, 95% CI (2.32, 8.27)], blood stasis constitution [OR = 2.17, 95% CI (1.06, 4.44)], phlegm-stasis mutual syndrome [OR = 3.64, 95% CI (1.87, 7.09)], and elevated non-high-density lipoprotein cholesterol [OR = 1.30, 95% CI (1.01, 1.69)] as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability, with an area under the receiver operating characteristic curve (AUC) of 0.818 [95% CI (0.781, 0.852)] in the training set and 0.816 [95% CI (0.779, 0.850)] in the validation set. The Hosmer-Lemeshow test showed good calibration (χ² = 4.55, P = 0.80), and the model's predictive ability was stable. When the threshold probability exceeded 5%, the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure, teeth-marked tongue, weak pulse, wiry pulse, phlegm-stasis mutual syndrome, blood stasis constitution, and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors, which showed good discrimination, calibration, and clinical utility, providing a scientific basis for predicting readmission events in patients with stable angina.
3.Improvement effects and mechanism of total secondary ginsenosides on hypertrophic changes in cardiomyocytes
Bin LI ; Jia LI ; Zhongjie YUAN ; Mingjun ZHU ; Shiyang XIE ; Yuan GAO ; Rui YU ; Xinlu WANG
China Pharmacy 2025;36(12):1430-1435
OBJECTIVE To investigate the ameliorative effects and potential mechanism of total secondary ginsenosides (TSG) on hypertrophic changes of primary cardiomyocytes stimulated by angiotensin Ⅱ (Ang Ⅱ). METHODS Primary cardiomyocytes were isolated from the hearts of neonatal SD rats and divided into the following groups: control group, AngⅡ group (2 µmol/L), TSG group (7.5 µg/mL), PFK-015 group [6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) inhibitor, 10 nmol/L], and TSG+PFK-015 group (TSG 7.5 µg/mL+PFK-015 10 nmol/L). The surface area, protein synthesis, energy metabolism-related indicators [free fatty acid (FFA), coenzyme A (CoA), acetyl coenzyme A (acetyl-CoA)], and the expressions of glycolysis-related factors [hypoxia-inducible factor 1α (HIF-1α), glucose transporter protein 4 (GLUT-4), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1) and PFKFB3] in primary cardiomyocytes of each group were measured. RESULTS Compared with the control group, the surface area of primary cardiomyocytes and protein synthesis were significantly increased, the content of FFA, protein and mRNA expressions of HIF-1α, LDHA, PDK1 and PFKFB3 were significantly increased or up-regulated in the AngⅡ group, while the contents of CoA and acetyl-CoA, the protein and mRNA expressions of GLUT-4 were significantly decreased or down-regulated (P<0.05). Compared with the AngⅡ group, both TSG group and PFK-015 group showed significant improvements in these indexes, with the TSG+PFK-015 group generally demonstrating superior effects compared to either treatment alone (P<0.05). CONCLUSIONS TSG can reduce the surface area of AngⅡ-induced primary cardiomyocytes, decrease protein synthesis, and inhibit their hypertrophic changes. These effects may be related to improving energy metabolism and the inhibition of glycolysis activity.
4.Effect of relaxing needling at the contracted sites of meridian-muscle regions in the patients with post-stroke shoulder-hand syndrome at acute stage.
Mingjun YING ; Min YUAN ; Zhiliang LAI ; Zhiling LV ; Yiming LAI ; Chao LI ; Jingjing ZHOU ; Guiping HE ; Weifang ZHU
Chinese Acupuncture & Moxibustion 2025;45(12):1699-1704
OBJECTIVE:
To investigate the effect of relaxing needling at the contracted sites of meridian-muscle regions in the patients with post-stroke shoulder-hand syndrome (SHS) at acute stage.
METHODS:
Eighty patients with post-stroke SHS at acute stage were randomized into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 1 case was eliminated). In the control group, the routine medication, basic rehabilitation training, and hyperbaric oxygen therapy were administered. In the observation group, besides the treatment as the control group, relaxing needling was delivered at the contracted sites of meridian-muscle regions. These contracted sites were distributed along three yin meridians of hand and three yang meridians of hand on the affected upper limbs. The intervention was given once daily, 5 times a week and for 4 weeks. Before and after treatment, the scores of visual analogue scale (VAS) for pain, edema degree, modified Barthel index (MBI), and Fugl-Meyer assessment (FMA) for motor function, and the integrated electromyography (iEMG) of surface electromyogram (sEMG) were observed in the two groups. The curative effect was evaluated after treatment and in follow-up of 2 months after treatment in the two groups.
RESULTS:
After treatment, VAS scores and the scores of edema degree were reduced when compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than those in the control group (P<0.05). MBI and FMA scores increased after treatment compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05) after treatment. The iEMG values of the biceps brachii, triceps brachii, and wrist extensors were elevated after treatment in comparison with those before treatment (P<0.05) in the two groups, and the values in the observation group were larger than those in the control group after treatment (P<0.05). The total clinical effective rate in the observation group was 92.3% (36/39), which was better than that of the control group (74.4%, 29/39, P<0.05) after treatment; and that of the observation group was 97.4% (38/39), which was better than 82.1% (32/39) in the control group (P<0.05) in follow-up.
CONCLUSION
Relaxing needling at the contracted sites of meridian-muscle regions in treatment of post-stroke SHS at acute stage can attenuate the symptoms such as upper limb pain, swelling and spasm, improve motor function and the activity of daily living of patients.
Humans
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Male
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Female
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Middle Aged
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Acupuncture Therapy
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Aged
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Meridians
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Stroke/complications*
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Reflex Sympathetic Dystrophy/etiology*
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Adult
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Acupuncture Points
5.Effect of Modified Zhigancao Granules (炙甘草汤加味颗粒) on Early Recurrence Following Radiofrequency Ablation in Patients with Atrial Fibrillation of Qi-Yin Deficiency Syndrome:A Randomized,Double-Blind,Placebo-Controlled Trial
Yucai HU ; Boyong QIU ; Jingjing WEI ; Bin LI ; Zuoying XING ; Huixia PENG ; Mingjun ZHU ; Yongxia WANG
Journal of Traditional Chinese Medicine 2025;66(23):2460-2466
ObjectiveTo evaluate the clinical effectiveness and safety of Modified Zhigancao Granules (炙甘草汤加味颗粒) for preventing the early recurrence following radiofrequency ablation in patients with atrial fibrillation (AF) of qi-yin deficiency syndrome. MethodsA multi-center, randomized, double-blind, placebo-controlled trial was designed. A total of 116 patients with atrial fibrillation of qi-yin deficiency syndrome who underwent radiofrequency ablation for the first time were enrolled from 3 centers, and they were randomly divided into a treatment group (59 cases) and a control group (57 cases). Both groups received basic western medicine treatment after surgery. In addition, the treatment group was given oral Modified Zhigancao Granules, while the control group was given oral placebo granules. The dosage for both groups was 20 g each time, twice a day, with continuous treatment for 12 weeks. The recurrence of atrial fibrillation in both groups was recorded at 24 hours, 4 weeks, 8 weeks, and 12 weeks after surgery. The serum levels of B-type natriuretic peptide (BNP), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) were detected before treatment and 12 weeks after treatment in both groups. The scores of Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) Questionnaire (including scores of the daily life dimension, symptom dimension, treatment worry dimension, treatment satisfaction dimension, and total score) and traditional Chinese medicine (TCM) syndrome scores were compared before treatment and at 4 weeks, 8 weeks, and 12 weeks between groups. Safety indicators such as blood routine, urine routine, liver function, and renal function were monitored before and after treatment. ResultsNine of the treatment group and seven of the control group dropped out. Finally, 50 patients in each group were included in the statistical analysis. At 24 hours, 4 weeks, 8 weeks, and 12 weeks after surgery, the recurrence rates of AF in the treatment group were 2.0% (1/50), 2.0% (1/50), 4.0% (2/50), and 10.0% (5/50), respectively; while those in the control group were 2.0% (1/50), 26.0% (13/50), 28.0% (14/50), and 34.0% (17/50), respectively. Compared with the control group at the same time points, the early recurrence rates of AF in the treatment group were significantly lower at 4 weeks, 8 weeks, and 12 weeks after surgery (P<0.01). Compared with the baseline within group, BNP, hs-CRP, IL-6, and TNF-α in the treatment group all decreased after 12 weeks of treatment (P<0.05); the difference in hs-CRP levels (before vs. after treatment) in the treatment group was higher than that in the control group (P<0.01). Compared with the baseline within group, both groups showed decreases in the total score of AFEQT Questionnaire, scores of the daily life dimension, treatment worry dimension, symptom dimension, and TCM syndrome scores at 4 weeks, 8 weeks, and 12 weeks after treatment. Meanwhile, the score of the treatment satisfaction dimension of AFEQT increased in both groups (P<0.01), and the improvements in all the above scores in the treatment group were superior to those in the control group at all time points (P<0.05 or P<0.01). All safety indicators of patients in both groups were within the normal range before treatment and at 12 weeks after treatment, and no adverse reactions or adverse events occurred in either group. ConclusionModified Zhigancao Granules can reduce the early recurrence rate following radiofrequency ablation in AF patients with qi-yin deficiency syndrome, improve clinical symptoms and quality of life, suppress inflammatory response, and show good safety.
6.Screening and experimental validation of hub genes for myocardial isch-emia-reperfusion injury based on bioinformatics
Jianru WANG ; Xingyuan LI ; Shiyang XIE ; Yanling CHENG ; Hongxin GUO ; Mingjun ZHU ; Rui YU
Chinese Journal of Pathophysiology 2024;40(3):473-483
AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.
7.Efficacy of concurrent tumor treating fields and chemoradiation in patients with high-grade glioblastoma
Zixuan WANG ; Dan ZONG ; Huanfeng ZHU ; Xiao WANG ; Mingjun DING ; Wenjie GUO ; Jiajun ZHENG ; Xia HE
Chinese Journal of Radiation Oncology 2024;33(4):307-313
Objective:To evaluate the safety and efficacy of tumor-treating fields (TTFields) and chemoradiation in patients with high-grade glioblastoma.Methods:Clinical data of 38 patients admitted to the Jiangsu Cancer Hospital from September 2021 to May 2023 who were diagnosed with high-grade glioblastoma (36 cases of World Health Organization grade Ⅳ and 2 cases of grade Ⅲ) were retrospectively analyzed. All patients received TTFields combined with concurrent chemoradiation after surgery. Response assessment in neuro-oncology (RANO) criteria was used to evaluate the glioma responses as tumor remission, stable or progression. Common terminology criteria for adverse events v5.0 and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Treatment compliance was assessed by data on the NovoTTF-200A therapeutic device, calculated as a percentage of daily TTFields usage time. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test.Results:The median duration of treatment with TTFields in 38 patients was 20 h (rang: 2.4-22.6 h), and the median treatment compliance was 83% (range: 10%-94%). After 42 days of TTFields combined with concurrent chemoradiation, 12 patients who underwent complete tumor resection were assessed as stable according to RANO criteria. Among the 26 patients who underwent partial tumor resection, 23 (88%) were evaluated as disease remission according to RANO criteria. The 7-, 10-, 13-month progression-free survival rate was 81.0%、64.0%、49.5%, repectively. The common adverse events included grade 1 (45%) and grade 2 (8%) dAE, without grade 3-4 dAE. Typical presentations included contact dermatitis, blisters, lesions or ulcers, and abscesses. The median follow-up time was 10.0 months (range: 1.6-21.3 months). At follow-up as of July 2023, 26 of the 38 patients were stable and 12 had disease progression (8 died).Conclusion:The preliminary results show that TTFields combined with chemoradiation is effective, safe and reliable treatment for high-grade glioblastoma.
8.Effects of Lijin Zhenggu Therapy combined with heat supplementing needles on cartilage damage, immune balance, and liver X receptor nuclear factor NF-κB pathway in knee arthritis of New Zealand white rabbits
Chan WANG ; Mingjun XU ; Wei ZUO ; Haitao ZHAO ; Cheng CHEN ; Wenyan YAN ; Xueping ZHU
International Journal of Traditional Chinese Medicine 2024;46(5):600-606
Objective:To explore Lijin Zhenggu Therapy combined with heat supplementing needles on cartilage damage, immune balance, and liver X receptor NF-κB in knee osteoarthritis of New Zealand white rabbits.Methods:Totally 60 New Zealand white rabbits were divided into normal group, model group, Lijin Zhenggu Therapy group, heat supplementing needles group, and a combination group using random number table method, with 12 rabbits in each group. Except for the normal group, all other groups were established with knee osteoarthritis models. The Lijin Zhenggu Therapy group was treated with Lijin Zhenggu Therapy, the heat supplementing needles group was treated with heat supplementing needles, the combination group was treated with Lijin Zhenggu Therapy combined with heat supplementing needles. The pain threshold of each group of white rabbits was observed using a pain meter; HE staining was used to observe the morphology of cartilage damage in each group of white rabbits; ELISA was used to detect PGE 2, IL-1β and β-EP in the articular cartilage tissue of white rabbits in each group; PCR was used to detect the levels of LXRα and NF-κB mRNA. Western blot was used to detect toll like receptor 4 (TLR4), myeloid differentiation factor (MyD88), interferon regulatory factor-7 (IRF-7) in synovial tissue of rabbits in each group. Results:Compared with model group, the pain threshold of rabbits in heat supplementing needles group, Lijin Zhenggu Therapy group and combination group increased ( P<0.05); the levels of PGE 2 and IL-1β decreased ( P<0.05), while the level of β-EP increased ( P<0.05). LXRα mRNA level increased ( P<0.05), and NF-κB mRNA level decreased ( P<0.05); the expressions of TLR4, MyD88, IRF-7 and NF-κB P65 in synovial tissue decreased ( P<0.05). Conclusions:Lijin Zhenggu Therapy combined with heat supplementing needles can reduce the levels of PGE 2 and IL-1β, increase β-EP level, improve pain and cartilage tissue morphology. The mechanism may be related to the regulation of liver X receptor nuclear factor NF-κB pathway, reduction of inflammatory reactions and immunity maintaining.
9.Exploration on the mechanism of acupuncture and moxibustion combined with sand therapy on bone biomechanics and immune function of knee osteoarthritis rabbits based on G protein coupled signaling pathway
Mingjun XU ; Liangyu QIU ; Chan WANG ; Cheng CHEN ; Xueping ZHU
International Journal of Traditional Chinese Medicine 2024;46(6):737-742
Objective:To explore the mechanism of acupuncture combined with sand therapy on bone biomechanics and immune function in rabbits with knee osteoarthritis based on G protein coupled signal.Methods:Totally 35 rabbits were randomly divided into normal group, model group, sand therapy group, acupuncture and moxibustion group and combined group, with 7 rabbits in each group. Except for the normal group, all other groups were prepared with knee osteoarthritis models. After 12 h modeling, rabbits in the sand therapy group and the combined group were treated with sand therapy. Rabbits in the acupuncture and moxibustion group and the combined group received acupuncture stimulation intervention therapy. Rabbits in normal group and model group only moved freely. The levels of IgG, IgM and IgA in serum and IL-1β and TNF-α were detected by ELISA method. The biomechanical properties of femur were measured by American Instron universal material experimental machine. The pathological changes of rabbits in each group were observed by HE staining. Protein expression levels of Gαs, cAMP and Gi in rabbit cartilage tissues were detected by Western blot.Results:Compared with model group, the levels of IgG, IgM and IgA increased ( P<0.05)l the levels of IL-1β and TNF-α decreased ( P<0.05); the maximum load, breaking load, structural stiffness and capacity absorption of rabbits in sand therapy group, acupuncture group and combined group increased ( P<0.05); the expressions of Gαs and cAMP protein increased ( P<0.05), while the expression of Gi protein decreased ( P<0.05). Conclusion:Acupuncture combined with sand therapy in the treatment of knee osteoarthritis can effectively improve the bone strength of osteoarthritis, reduce the inflammatory response, balance the expression of G protein and improve the imbalance of immunoglobulin.
10.Effects of Compound Dahuang Powder combined with acupuncture on synovial ultrastructure, pathological angiogenesis and Ras/Raf signal of synovial cells in rats with rheumatoid arthritis
Mingjun XU ; Liangyu QIU ; Chan WANG ; Cheng CHEN ; Xueping ZHU
International Journal of Traditional Chinese Medicine 2024;46(8):999-1005
Objective:To investigate the effects of external application of Compound Dahuang Powder combined with acupuncture on the synovial ultrastructure, pathological angiogenesis, and Ras/Raf signaling pathway in rheumatoid arthritis rats.Methods:Totally 100 SPF grade SD rats were selected and divided into normal group, model group, acupuncture group, external application group, and combination group according to random number table method, with 20 rats in each group. Except for the normal group, Freund's complete adjuvant was injected into the bilateral plantars to establish a rheumatoid arthritis model. One week after modeling, the acupuncture group received acupuncture at "Yinlingquan (SP9)" and "Sanyinjiao (SP6)" for 30 minutes, with continuous intervention for 6 days and 7 days as one course of treatment, for a total of 3 courses of intervention. The external application group of rats applied compound Dahuang Powder on the right hind foot and ankle joint, 10 g/time, twice a day, for 7 days as one course of treatment, with a total of 3 intervention courses; the combination group received a combined intervention of acupuncture and external application of compound Dahuang Powder. No intervention was performed in the normal group and model group. The levels of TNF-α and IL-1β in serum of rats in each group were detected using enzyme-linked immunosorbent assay. Transmission electron microscopy was used to observe the ultrastructure of synovial cells. HE staining was used to observe the morphology of synovial tissue. Immunohistochemistry was used to detect vascular endothelial growth factor (VEGF) and its receptor VEGFR2 in synovial tissue. Western blot and RT qPCR were used to detect Ras/Raf protein and mRNA in synovial tissue, respectively.Results:Compared with model group, the levels of TNF-α and IL-1β in serum of rats in acupuncture group and external application group decreased ( P<0.05), the expressions of VEGF and VEGFR2 decreased ( P<0.05), and the expressions of Ras and Raf protein and mRNA in acupuncture group and external application group decreased ( P<0.05). Compared with acupuncture group and external application group, the levels of TNF-α and IL-1β in serum of rats in the combination group decreased ( P<0.05), the expressions of VEGF and VEGFR2 decreased ( P<0.05), and the expressions of Ras and Raf protein and mRNA in the combination group decreased ( P<0.05). The results of synovial cell ultrastructure showed that the nuclear membrane of synovial cells in normal group was good, and the nuclear membrane in model group was seriously damaged. The acupuncture group and external application group had different degrees of improvement, and the combination group had the most significant improvement. HE staining results showed that the joint synovial tissue of the normal group was normal, the joint synovial tissue of the model group had a large amount of inflammatory infiltration, the joint synovial injury of the acupuncture group and the external application group was slightly improved, and the pathological injury of the combined group was significantly reduced. Conclusion:The combination of external application of compound Dahuang Powder and acupuncture can regulate angiogenesis related factors, regulate the Ras/Raf signaling pathway, and improve the ultrastructure of synovial cells in rheumatoid arthritis model rats.

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