Network pharmacology-based approach to investigate the mechanisms of Yiyi Fuzi Baijiang Powder in the treatment of malignant tumors

Objective:To systematically investigate the main active components,targets,target-related diseases and action mechanism of Yiyi Fuzi Baijiang powder(YFBP)of Zhang Zhongjing,a Chinese physician of Eastern Han Dynasty of China(3 century A.D.)using the method of network pharmacology.Methods:The active components of YFBP were identified from several databases(TCMSP,TCM Database@Taiwan and TCMID).The potential active compounds were screened based on oral bioavailability and drug-like index in the TCMSP database.DrugBank,TCMSP,and TCMID database searches were performed to predict target-related diseases.Biological functions and KEGG pathway outcomes of all potential targets were analyzed using the DAVID database.Results:A total of 24 active compounds of YFBP,133 related targets,and 305 potential related diseases were obtained.These results showed that YFBP may treat inflammation,pain,and cancer.The functional enrichment analysis indicated that YFBP probably exerts its therapeutic effects by regulating neuroactive ligand-receptor interactions,the TNF signaling pathway,and the PI3K-Akt signaling pathway.Conclusion:This study provides preliminary confirmation that YFBP has the great potentials to treat inflammation,pain,and tumors,which supports Zhang Zhongjing’s original intention to treat intestinal carbuncle with ancient prescription YFBP,but also provides a scientific basis for its treatment in the malignant tumors.

Dahuang Fuzi decoction reduces inflammation levels and alleviates intestinal mucosal barrier damage in septic rats

Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.

Research progress on synergetic effects of Fuzi(Radix Aconiti Lateralis Preparata)and Tubeimu(Rhizoma Bolbostemmatis)/Gualou(Trichosanthes kirilowii Maxim)

The compatibility of Chinese herbs is the focus and the difficulty in traditional Chinese medicine research,and it has an important guiding role for clinical medicine.Some scholars believe that the Fuzi(Radix Aconiti Lateralis Preparata,FZ)compatibility with Tubeimu(Rhizoma Bolbostemmatis,TBM)/Gualou(Trichosanthes kirilowii Maxim,GL)does not meet the Chinese medicine theory of“eighteen incompatibilities”.However,this combination has been used many times in many clinical medications.This study reviewed the research progress of pharmacological effects of FZ,and FZ compatibility with TBM/GL,in order to correctly understand and apply the“eighteen incompatibilities”drugs,and provide a reference for further exploration of the combined application in clinical treatment.

Efficacy and safety of Mahuang Fuzi Xixin Decoction on sick sinus syndrome： Ameta – analysis

Objective： To evaluate the efficacy and safety of Mahuang Fuzi Xixin Decoction on sick sinus syndrome andprovide evidence for clinical practice. Methods： Randomized controlled trials of all the languages of MahuangFuzi Xixin Decoction on sick sinus syndrome were collected by computer search and manual retrieval. Theretrieval time was from January 2000 to January 2017. According to the inclusion and exclusion criteria, 2reviewers independently selected and extracted data, then evaluated the quality, cross-checked the information andevaluated the quality of menthodology. Through discussion or third reviewer to help solve the divergence, RevMan5.3 software was used to perform meta analysis. Results： A total of 7 documents （n = 612） were finally enrolled,with 358 in Mahuang Fuzi Xixin Decoction group （treatment group） and 254 in control group. Meta analysisshowed that the treatment （86.9%） was more effective than the control （70.1%）, the difference was statisticallysignificant （RR = 1.25, 95% CI：（1.15-1.37）, P 〈 0.001）; the treatment （17.0%） was safer than the control （49.8%）,the difference was statistically significant （RR=0.23,95% CI：（0.06-0.93）, P =0.04）. Conclusion： The existingclinical studies suggest that Mahuang Fuzi Xixin Decoction on sick sinus syndrome is effective and safe; due to thelimited quality of the enrolled documents, the above conclusions need more high-quality randomized controlledtrials to be verified.

Fuzi promoted the formation of myelin sheath in Schwann cells induced by high glucose

OBJECTIVE Diabetic peripheral neuropathy(DPN)is the cause of considerable morbidity and mortality indiabetic patients.The loss of nerve fibersis the main pathological characteristics of the DPN and the pathway of Oct6-Krox20 plays an important role in the formation of myelin sheath.In our previous study,we found that Fuzi(Radix aconite lateral ispreparata)could significantly improve the nerve conduction deficits and thermal hypoalgesia deficits in the diabetic rats,but the underlying molecular mechanisms have not been established.The aim of this study is to investigate the expression of Oct6,Krox20,myelin basic protein(Mbp)and myelin protein zero(Mpz)in Schwann cells and analyze the effect of Fuzi in the formation of myelin sheath.METHODS There were six groups in the study.In the control group,thecells weresupplemented with normal cell culture medium.In the mannitol group,the cells were fed with normal glucose plus mannitol.In the model group,the cells were supplemented with high glucose medium(75 mmol·L-1).In the other group,the cells weretreated with high glucose medium(75mmol·L-1)plus different concentrations of Fuzi(0.1,1.0 and 10.0μg·mL-1).After three days,real-time PCR was used to detect gene expression.RESULTS Compared with the control group,the model group showed lowerexpression of Oct6,Krox20,Mbp and Mpz.In comparison to the model group,Fuzi(0.1,1.0and 10.0μg·mL-1)increased the expression of Oct6,Krox20,Mbp and Mpz.CONCLUSION These results demonstrate that Fuzi enhances the protein of myelin sheath through impacting the pathway of Oct6-Krox20.

Clinical Study on Fuzi Lizhong Pill in Treating Salivation after Taking Clozapine for Schizophrenia

[Objectives]To observe the clinical effect of Fuzi Lizhong pills for salivation after taking clozapine in schizophrenia.[Methods]A total of 45 cases of schizophrenia patients with salivation after taking clozapine only were selected as the study subjects and randomly divided into two groups according to enrollment order.The control group(22 cases)was treated with propantheline bromide tablets and the treatment group(23 cases)were treated with Fuzi Lizhong pills combined with propantheline bromide tablets.Clinical effects and adverse reactions were compared between the two groups.Chinese medicine syndrome scores,scores of severe degree of salivation and levels of serum cholinesterase were compared between the two groups before treatment,after one-week treatment and after two-week treatment.[Results]The total clinical effective rate was 86.96%in the treatment group,higher than that of 59.09%in the control group(P<0.05).When compared with those before treatment,Chinese medicine syndrome scores of short breath and lack of strength,lassitude of spirit and somnolence,poor appetite,spontaneous sweating and dyspnea,and salivation as well as scores of salivation in Rating Scale for Extrapyramdal Side Effects(RSESE)and the severe degree of salivation in the two groups were decreased after 1 week and 2 weeks treatment(P<0.05),and levels of serum cholinesterase were increased(P<0.05).When compared with those in the control group after one-week and two-week treatment,Chinese medicine syndrome scores of short breath and lack of strength,lassitude of spirit and somnolence,poor appetite,spontaneous sweating and dyspnea,and salivation as well as scores of salivation in RSESE and the severe degree of salivation in the treatment group at the same period were lower(P<0.05),and level of serum cholinesterase was higher(P<0.05).There was no significant difference in the comparison of incidence of adverse reactions between the two groups(P>0.05).[Conclusions]Fuzi Lizhong pills combined with propantheline bromide tablets can improve clinical symptoms of schizophrenia patients with salivation after taking clozapine,and enhance level of serum cholinesterase and clinical effect.

Study on the mechanism of Fuzi in the treatment of allergic rhinitis based on network pharmacology and experimental validation

Objective:To study the key target genes and signaling pathways in the treatment of Allergic Rhinitis(AR)with Radix Aconiti Lateralis Preparata(aka Fuzi).Methods:The TCMPS and PubChem databases were used to screen the active ingredients and target genes of Fuzi using oral bioavailability and drug similarity as screening conditions,and the GeneCards database was used to screen the target genes of AR.The online tool Venny2.1 was used to screen the target genes of Fuzi for the treatment of Allergic Rhinitis;the STRING database was used to obtain the protein-protein interaction(PPI)network of drug-disease targets,and the key target genes were identified by the MCC algorithm.The potential biological processes and signaling pathways were identified by GO enrichment and KEGG enrichment analysis.Finally,animal experiments were conducted to demonstrate the therapeutic effect ofFuzi on Allergic Rhinitis.Results:The TCMSP,PubChem and GeneCards databases were used to screen the 21 active compound components of Fuzi and 68 potential therapeutic target genes of Fuzi for Allergic Rhinitis.PPI network analysis identified the top ten key target genes,namely:PTGS2,TNF,IL6,AKT1,ALB,STAT3,CCL2,CXCL8,VEGFA and JUN,GO functional and KEGG pathway enrichment analysis showed that the significantly enriched functions and pathways of Fuzi on Allergic Rhinitis were closely related to Allergic Rhinitis.Finally,animal experiments were conducted to verify that Fuzi is effective in the treatment of Allergic rhinitis.Conclusion:Increased expression of IL-6 and TNF-αin nasal mucosal tissues of patients with Allergic Rhinitis was positively correlated with indicators related to the disease activity of AllergicRhinitis.Fuzi ameliorated the inflammatory changes in mice with Allergic Rhinitis by inhibiting the activation of Toll-like signaling pathway in the nasal mucosa and decreasing the expression activity of IL-6 and TNF-α.

Mahuang Xixin Fuzi decoction protects against ovalbumin-induced allergic rhinitis by inhibiting type 2 innate lymphoid cells in mice

Objective:As a traditional herbal formula,Mahuang Xixin Fuzi decoction(MXFD)has been used to treat allergic rhinitis(AR).It regulates the transcription factor GATA3 in T cells,blocks Th2 skewing and rebalances the Th1/Th2 immunity.Type 2 innate lymphoid cells(ILC2s)are closely associated with GATA3.However,it remains unknown whether ILC2s could be one mechanism through which MXFD acts.We sought to elucidate the efficacy and mechanism of action of this decoction in AR treatment.Methods:Forty C57BL/6J female mice were equally divided into control,model,loratadine-and MXFDtreated groups in random.AR was induced by ovalbumin(OVA),and then treatment with loratadine or MXFD was administered.AR scores were evaluated and compared before and after treatment.Pathological changes in the nasal mucosa and lung were observed using hematoxylin-eosin staining of tissue samples.Activation of ILC2 in nasal mucosa was assessed by immunofluorescence and quantitative polymerase chain reaction analysis.ILC2 cell count in lungs was measured by flow cytometry and levels of interleukin-(IL)4,IL-5 and IL-13 in serum were detected by ELISA.Results:The decoction alleviated the symptoms of AR in mice,improved vascular congestion and expansion,glandular hyperplasia and inflammatory cell infiltration in mouse nasal mucosa and slowly improved the interstitial pneumonia and lesions.Meanwhile,MXFD reduced the number and percentage of ILC2s in the nasal mucosa and lungs,downregulated the expression of GATA3 mRNA and RORa mRNA,and reduced the related inflammatory cytokine levels,including IL-4,IL-5 and IL-13.Conclusion:These data suggest that inhibition of ILC2s by MXFD may be an important means by which to treat AR.

Therapeutic Analysis of Fuzi Lizhong Wan with Trimebutine in the Treatment of Diarrhea Type lrritable Bowel Syndrome

Objective:To evaluate the clinical efficacy ofFuzi Lizhong Wan and trimebutine in the treatment of diarrhea irritab1e bowel syndrome.Methods:A tota1 of 90 patients with diarrhea irritable Dow1 syndrome were divided intocontro1 group(n=45)and treatment group(n=45)using the random.number table method.Patients in the control group were po administered withtrimebutine 0.2 g.three time daily for 4 weeks.Patients in the treatment group were po administered with Fuzi Lizhong Wan 9 g,three time daily for 4 weeks on the basis of the control group.The clinical efficacy and the TCM symptom scores were evaluated after treatment.The serological indicators in two groups were compared before and after treatment.Results:After treatment,the clinica1 efficacy and the TCM symptom scores in treatment group were significantly 1ower than that in contro1 group(P<0.05).The 1evels of serological indicators in both groups improved significant1y,and those in the treatment group were better than the control group(P<0.05).Conclusion:Combined therapy of Fuzi Lizhong Wan and trimebutine in the treatment of diarrhea type irritable bowe1 syndrome has a significant effect,which canrelieve clinical symptom;and reduce visceral sensitivity,and improve leve1s of inflammatory and quality of life.So it is suggested to be applied.

Mechanism of Yiyi Fuzi Baijiang powder in treatment of ulcerative colitis on network pharmacology and m olecular docking

Objective:To explore the mechanism of Yiyi Fuzi Baijiang p owder in treatment of ulcerative colitis in Coix Lacryma-jobi based on network pharmacology and molecular docking technology.Methods:Search for Yiyi Fuzi Baijiang powder’s active ingredient by traditional Chinese medicine database and analysis platform system pharmacology,Genecards,Uniprot database and Cytoscape software were used to construct the active component-ulcerative colitis disease target network,and gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed,Autodock Vina was used for molecular docking verification.Results:Quercetin,luteolin,kaempferol,chrysin,macroanol B,β-sitosterol,stigmasterol,deltoan and rhizoctonine may play a role in the treatment of ulcerative colitis.KEGG pathway enrichment analysis showed that Yiyi Fuzi Baijiang p owder mainly involved i nterleukin-17 signaling pathway and cancer pathway,among which the key targets were PTGS2,HSP90AA1 and CASP3 and had a good binding activity with 10 main active components.Conclusion:The treatment of ulcerative colitis by Yiyi Fuzi Baijiang p owder may be mainly through quercetin,luteolin,macroanol B,β-sitosterol and other chemical components involved in cancer pathway,i nterleukin-17 signaling pathway acting on PTGS2,HSP90AA1,CASP3 and other disease targets in response to inorganic substances,response to cytokines and other biological processes f actor receptor binding and other molecular functions to achieve the purpose of treating u lcerative colitis.

Development and validation of a HPLC-UV-ESI-MS method for the simultaneous quantitation of ten bioactive compounds in Dahuang Fuzi Tang

AIM: To develop a high performance liquid chromatography(HPLC) coupled with electrospray ionization mass spectrometry(ESI-MS) and ultraviolet(UV) detector method for the acid-alkaline simultaneous determination of ten bioactive compounds, and analyze the effect of compatible medicinal plants on the concentration of components in Dahuang Fuzi Tang(DFT). METHOD: The chromatographic separation was performed on a Hypersil BDS C18 analytical column by gradient elution with acetonitrile and formate buffer(containing 0.15% formic acid, V/V) at 25 °C with a flow rate of 1.0 mL ·min–1 and UV detection at 280 nm. Four of the ten compounds in DFT were identified and their MS fragments were elucidated by HPLC-ESI-MS, and the contents of the six compounds were determined by HPLC-UV. RESULTS: All calibration curves showed good linear regression(r2 ≥ 0.9990). The limits of detection and limits of quantification were 0.021–0.155 μg·mL –1 and 0.076–0.520 μg·mL –1, respectively. Overall precision RSD(intra-day and inter-day) were less than 2.96%, and the average recoveries were 98.35%–101.45%, with RSD ranging from 1.54% to 3.01% for the analytes. CONCLUSION: The developed method can be applied for the quality control and provide analytical evidence on the chemical basis and combinational principles of DFT.

Efficacy of Renshen(Radix Ginseng) plus Fuzi(Radix Aconiti Lateralis Preparata) on myocardial infarction by enhancing autophagy in rats

OBJECTIVE:To elucidate the protective effects of Renshen(Radix Ginseng)and Fuzi(Radix Aconiti Lateralis Preparata)on myocardial infarction(MI)through regulating myocardial autophagy.METHODS:Thirty-one male Sprague-Dawley rats were randomized into five groups(n=6 or 7 for each).After treatment for 3 weeks,electrocardiogram(ECG)and cardiac function were recorded.Hematoxylin and eosin(HE)staining was used to detect pathological changes in the heart.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum B-type brain natriuretic peptide(BNP),cardiac troponin T(c Tn T),tumor necrosis factor-α(TNF-α),and serum inflammatory cytokines.Metabolomic analysis was used to identify differential biomarkers of MI in rats.Immunohistochemistry and western blotting were used to detect BNP,cTnT,TNF-α,LC3B,Beclin-1,p62,and adenosine monophosphate activated protein kinase(AMPK)expression in cardiac tissue.RESULTS:Fuzi(Radix Aconiti Lateralis Preparata)alone or Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)markedly ameliorated cardiac dysfunction and abnormal ECGs,demonstrated by decreases in the heart weight/body weight ratio,BNP,and c Tn T.Pro-inflammation cytokine interleukin(IL)-1αsignificantly decreased and anti-inflammatory cytokine IL-10 significantly increased in Renshen(Radix Ginseng)single or Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)groups compared with the control group.HE results suggested that co-treatment produced a greater reduction in cardiomyocyte cross-sectional area than Renshen(Radix Ginseng)or Fuzi(Radix Aconiti Lateralis Preparata)alone.Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)reversed these changes to different degrees in MI rats.Furthermore,Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)down-regulated LC3 B,Beclin-1,and AMPK expression in cardiac tissue and upregulated p62 expression.CONCLUSIONS:Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)may have a greater effect on heart injury induced by MI in rats than Fuzi(Radix Aconiti Lateralis Preparata)treatment alone,and the underlying mechanism may be associated with the regulation of myocardial autophagy and anti-inflammation effects.These results provide fresh insight into the mechanism of co-treatment with Renshen(Radix Ginseng)and Fuzi(Radix Aconiti Lateralis Preparata)for MI.

Inhibitory effect of Sumu(Lignum Sappan) plus Fuzi(Radix Aconiti Lateralis Praeparata) on a lung carcinoma model

OBJECTIVE: To investigate the inhibitory effect of Sumu(Lignum Sappan) plus Fuzi(Radix Aconiti Lateralis Praeparata)(SF) on the growth and metastasis of Lewis lung carcinoma.METHODS: A lung carcinoma model was established by subcutaneously inoculating Lewis lung carcinoma cells into C57 BL/6 mice. The mice were randomly divided into four groups of 13 mice(control, low-dose, moderate-dose, and high-dose), and gavaged once-daily for 21 consecutive days. The rates of tumor inhibition, metastasis, and metastasis inhibition were observed. The differential expressions of s P-selectin and vascular endothelial growth factor C(VEGFC) were compared between the treatment groups and the control group.RESULTS: The tumor weights differed significantly between the treatment groups and the control group(P < 0.05). Administration of SF in the moderate-dosage and low-dose groups significantly inhibited the expression of s P-selectin and VEGFC(both P < 0.05), suggesting anti-tumor activity.CONCLUSION: SF can inhibit the growth and metastasis of Lewis lung carcinoma.

Research on Fuzi based on animal thermotropism behavior to discover if it has fewer "hot" characteristics without Ganjiang

OBJECTIVE:To investigate whether Fuzi(Radix Aconiti Praeparata) has fewer "hot" characteristics when administered without Ganjiang(Rhizoma Zingiberis).METHODS:Differences in the thermotropism behaviors of mice treated either with Fuzi(Radix Aconiti Praeparata),Ganjiang(Rhizoma Zingiberis) or the combination of the two given intragastrically were investigated using the Animal Thermotropism Behavior Surveillance System.The water intake volume,oxygen consumption volume,adenosine triphosphatase(ATPase) activity,total antioxidant capacity(T-AOC) and total superoxide dismutase(T-SOD) activity were determined during the investigation.RESULTS:When Fuzi and Ganjiang were administered together,the rate at which mice remained on a warm plate("remaining rate") and the times and distances of their movement were all significantly reduced(P<0.05).Compared with the Normal group,the reduction was 55.1%,48.3% and 44.8%,while compared with the Fuzi group,the reduction was 57.6%,34.3% and 36.0%,indicating that "cold" tropism was significantly increased.Compared with the Normal and Fuzi groups,the ATPase activity and the respiratory oxygen consumption volume of the Fuzi + Ganjiang group were significantly increased(P<0.05),suggesting an improvement in energy metabolism and showing a "hot" characteristic when Fuzi and Ganjiang are present together.Additionally,the T-AOC and T-SOD activity were significantly enhanced(P<0.05).CONCLUSION:The behavior of mice tending toward "cold" tropism can be regarded as a quantitative reflection of Fuzi having fewer characteristics consistent w ith a "hot" nature when not used with Ganjiang,the functional mechanism of which may be a change in the ATPase activity in liver tissue.

Toxicity-efficacy converting of ginseng combined with Fuzi Banxia incompatibility in heart failure stage of cor pulmonale

Objective：Fuzi Banxia is one of eighteen antagonisms,previous studies have shown that the incompatibility could play special effects in the specific condition of diseases and appropriate compatible environment.The present study aims to evaluate the toxicity-efficacy of ginseng combined with Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale and to explore its mechanism.Methods：Monocrotaline（MCT）-induced cor pulmonale were used in this study.Ultra high-resolution small animal ultrasound real-time imaging system and the right heart catheterization were used to estimate cardiac function.Semi automatic biochemical analyzer was used to test myocardial enzyme LDH,CK,and CK-MB in serum.The heart tissues were stained with HE,and TUNEL assay was used to assess the pathomorphological changes and myocardial apoptosis.The expression of hypertrophy and apoptosis associated genes：ANP,BNP,β-MHC,Bax,and Bcl-2 in the right ventricle were determined by RT-PCR.Results：Fuzi Banxia combined with ginseng obviously attenuated mortality,decreased RVHI,and increased cardiac index;RVSP and m PAP were significantly reduced,and EF and FS were raised obviously;Myocardial enzymes LDH,CK,and CK-MB were pronounced attenuated;heart diameter reduced,right ventricular dilatation was significantly decreased,inflammatory cell infiltration notably reduced,and cardiac apoptosis rate was decreased obviously.Meanwhile,the expression of hypertrophy-related ANP,BNP,andβ-MHC m RNA were up-regulated,the expression of apoptosis-related Bax m RNA was down-regulated,and the expression of anti-apoptosis-related Bcl-2 m RNA and Bcl-2/Bax ratio were upregulated.Conclusion：Ginseng compatible environment could attenuate cardiac toxicity of Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale,and improve cardiac function,which may be related to the expression of hypertrophy and apoptosis associated genes,and thus delay the occurrence and development of heart failure.

麻黄附子细辛汤联合孟鲁司特钠对咳嗽变异性哮喘症状改善及外周血树突状细胞mDCs和pDCs水平的影响

目的分析麻黄附子细辛汤联合孟鲁司特钠对咳嗽变异性哮喘患儿症状改善及外周血髓样树突状细胞(myeloid dendritic cells,mDCs)和浆细胞样树突状细胞(plasmacytoid dendritic cells,pDCs)及肺功能的影响。方法选取医院2019年1月—2020年12月收治的132例咳嗽变异性哮喘患儿作为研究对象。按随机数字表法分为两组,对照组66例,在常规雾化治疗基础上给予孟鲁司特钠治疗;观察组66例,在对照组基础上给予麻黄附子细辛汤治疗。检测两组患儿治疗前、治疗后1、2、3、4周外周血mDCs、pDCs及mDCs/pDCs数据变化、症状改善情况及肺功能的影响。随访1年观察复发情况。结果两组治疗前后外周血mDCs比例没有变化(P>0.05);两组治疗后外周血pDCs比例均持续下降(P<0.05),但观察组治疗后2周和3周外周血pDCs比例低于对照组(P<0.05);两组治疗后mDCs/pDCs比值升高(P<0.05),但观察组治疗后2周和3周的mDCs/pDCs比值高于对照组(P<0.05)。治疗4周后,观察组早晚的咳嗽评分低于对照组(P<0.05);治疗4周后观察组肺功能各指标优于对照组(P<0.05);随访1年后,病例均未脱落,观察组复发率4.55%(3/66)低于对照组15.15%(10/66)(P<0.05)。结论麻黄附子细辛汤联合孟鲁司特钠治疗咳嗽变异性哮喘,更能快速降低外周血pDCs比例、提升mDCs/pDCs比值,有助于快速纠正患儿体内Th1/Th2的失衡状态同时减轻临床症状、优化肺功能,预后较好。

薏苡附子败酱散通过抗三结构域蛋白21-Toll样受体4-t-核因子-κB信号通路对类风湿关节炎MH7A细胞的影响

目的观察不同浓度薏苡附子败酱散对肿瘤坏死因子-α(TNF-α)诱导的类风湿关节炎成纤维细胞(MH7A)增殖、凋亡及炎症反应的影响,探究其作用机制。方法2022年2―8月,大鼠用不同浓度薏苡附子败酱散及蒸馏水灌胃制备含药血清;20μg/L的TNF-α处理的MH7A细胞记为TNF-α组,TNF-α+含药血清处理的MH7A细胞记为薏苡附子败酱散低浓度组、薏苡附子败酱散中浓度组、薏苡附子败酱散高浓度组,正常培养的MH7A细胞标记为对照组。细胞计数试剂盒(CCK8)、流式细胞术、酶联免疫吸附测定(ELISA)检测细胞的存活、凋亡及白细胞介素(IL)-1β、干扰素(IFN)-γ;蛋白质印迹法(WB)检测基质金属蛋白酶(MMP)-3、MMP-9、抗三结构域蛋白21(TRIM21)、Toll样受体4(TLR4)、t-核因子(NF)-κB p65、磷酸化(p)-NF-κB p65、p-NF-κB抑制因子(IκB)-α和t-IκB-α蛋白表达。pcDNA 3.1组(转染空载体)、pcDNA+TRIM21组(转染pcDNA 3.1+TRIM21)、薏苡附子败酱散中浓度+si-con组(转染si-con+4.70 g/kg含药血清)、薏苡附子败酱散中浓度+si-TRIM21组(转染si-TRIM21+4.70 g/kg含药血清)。结果与对照组相比,TNF-α组细胞存活率(105.07±1.90比185.67±3.06)、TRIM21(0.56±0.02比0.68±0.04)、MMP-3(0.18±0.00比0.63±0.02)、MMP-9(0.39±0.01比0.82±0.01)、TLR4(0.25±0.02比0.68±0.07)、p-NF-κB p65(0.24±0.01比0.68±0.06)、p-IκB-α(0.22±0.01比0.55±0.04)蛋白表达和IL-1β(31.65±0.66比101.93±0.60)、IFN-γ(8.53±0.16比63.76±1.35)含量均显著升高,凋亡率(6.54±0.06比1.17±0.08)均显著降低;与TNF-α组相比,薏苡附子败酱散低浓度组(185.67±3.06比153.77±3.09;0.68±0.04比0.37±0.02;0.63±0.02比0.47±0.02;0.82±0.01比0.73±0.01;103.2±0.7比92.93±0.85;66.3±1.45比54.47±1.46;0.68±0.07比0.53±0.05;0.68±0.06比0.53±0.06;0.55±0.04比0.47±0.01;1.84±0.07比6.67±0.28)、薏苡附子败酱散中浓度组(185.67±3.06比136.23±1.57;0.68±0.04比0.57±0.02;0.63±0.02比0.37±0.02;0.82±0.01比0.57±0.00;103.2±0.7比86.4±0.75;66.3±1.45比38.1±0.92;0.68±0.07比0.43±0.07;0.68±0.06比0.59±0.01;0.55±0.04比0.40±0.03;1.84±0.07比9.59±0.29)、薏苡附子败酱散高浓度组(185.67±3.06比143.47±1.50;0.68±0.04比0.47±0.02;0.63±0.02比0.41±0.05;0.82±0.01比0.62±0.00;103.2±0.7比89.63±0.42;66.3±1.45比40.17±0.90;0.68±0.07比0.51±0.06;0.68±0.06比0.69±0.07;0.55±0.04比0.41±0.02;1.84±0.07比8.89±0.08)细胞存活率、TRIM21、MMP-3、MMP-9蛋白和IL-1β、IFN-γ含量及TLR4、p-NF-κB p65、p-IκB-α蛋白表达均显著降低,凋亡率均显著升高(P<0.05);与pcDNA组相比,pcDNA+TRIM21组细胞TRIM21蛋白表达(0.24±0.03比0.51±0.04)、细胞凋亡率(1.61±0.11比12.43±0.61)均显著升高,MMP-3(0.64±0.02比0.41±0.04)、MMP-9(0.82±0.03比0.45±0.02)、IL-1β(110.63±0.55比90.93±0.60)、IFN-γ(64.5±0.82比48.1±1.25)及细胞存活率(179.03±0.74比120.07±0.60)均显著降低;敲减TRIM21显著抑制薏苡附子败酱散中浓度对损伤细胞的治疗作用且显著升高TLR4(0.45±0.06比0.61±0.02)、p-NF-κB p65(0.49±0.02比0.56±0.02)、p-IκB-α(0.38±0.01比0.62±0.01)的蛋白表达。结论薏苡附子败酱散增强TNF-α诱导的MH7A细胞的生存能力,其作用机制与上调TRIM21抑制TLR4-NF-κB信号通路活性有关。

附子理中汤联合足三里穴位注射配合循经热熨法对腹腔镜胃癌术后(脾胃虚寒证)患者胃肠激素、炎症反应、营养参数和血清MIP-3α、Stathmin的影响

目的:观察附子理中汤联合足三里穴位注射配合循经热熨法对腹腔镜胃癌术后(脾胃虚寒证)患者胃肠激素、炎症反应、营养参数和血清微管解聚蛋白(Stathmin)、巨噬细胞炎性蛋白-3α(MIP-3α)的影响。方法:选择2021年1月至2023年3月该院收治的胃癌患者126例,分组方式为随机数字表法。对照组42例患者(脱落2例,最终纳入40例)给予常规西医治疗,观察1组42例患者(脱落3例,最终纳入39例)在对照组的基础上给予足三里穴位注射配合循经热熨法治疗,观察2组42例患者(脱落2例,最终纳入40例)在观察1组的基础上给予附子理中汤治疗。比较三组患者的临床疗效,记录肛门首次排气时间、首次经口进食时间和首次排便时间;术后1、15 d测定三组患者营养参数(血清血红蛋白、转铁蛋白和白蛋白),检测炎症反应指标[血红素加氧酶-1(HO-1)、缺氧诱导因子-1α(HIF-1α)和白细胞介素6(IL-6)]、胃肠激素指标[胃泌素17(G-17)、胃动素(MTL)]及MIP-3α、Stathmin水平。结果:观察1组、观察2组患者的总有效率分别为94.87%(37/39)、97.50%(39/40),高于对照组的75.00%(30/40),差异有统计学意义(P<0.05);而观察2组与观察1组患者总有效率的差异无统计学意义(P>0.05)。观察2组患者肛门首次排气时间、首次经口进食时间和首次排便时间短于对照组、观察1组,且观察1组患者短于对照组,差异均有统计学意义(P<0.05)。术后15 d,观察2组患者转铁蛋白、血红蛋白和白蛋白水平高于对照组、观察1组,且观察1组患者高于对照组;观察2组患者HO-1、HIF-1α和IL-6水平低于对照组、观察1组,且观察1组患者低于对照组;观察2组患者G-17、MTL水平高于对照组、观察1组,且观察1组患者高于对照组;观察2组患者Stathmin、MIP-3α水平低于对照组、观察1组,且观察1组患者低于对照组,上述差异均有统计学意义(P<0.05)。结论:附子理中汤联合足三里穴位注射配合循经热熨法治疗腹腔镜胃癌术后患者,可减少炎症反应,调节胃肠激素和营养参数,降低Stathmin、MIP-3α水平,促进疾病康复,提高临床疗效。

桂枝附子汤加味联合温针灸治疗肾虚寒凝型类风湿关节炎的效果及对miR-24、miR-132表达的影响

目的探讨桂枝附子汤加味联合温针灸治疗肾虚寒凝型类风湿关节炎(RA)的效果及对miR-24、miR-132表达的影响。方法选取2021年3月至2022年3月收治的80例RA患者为研究对象,采用随机数字表法将其分为对照组与观察组,各40例。对照组采用常规西药治疗,观察组在对照组基础上加桂枝附子汤加味联合温针灸治疗。比较两组的治疗效果。结果观察组的治疗总有效率为95.00%,高于对照组的77.50%(P<0.05)。治疗后,观察组的miR-24表达量高于对照组,miR-132表达量低于对照组(P<0.05)。治疗后,观察组的类风湿因子(RF)、红细胞沉降率(ESR)、白细胞介素-1(IL-1)、基质金属蛋白酶-3(MMP-3)水平低于对照组,差异具有统计学意义(P<0.05)。结论桂枝附子汤加味联合温针灸治疗肾虚寒凝型RA,不仅能够提高治疗效果,还能调节miR-24、miR-132表达量,抑制炎性因子水平,促进炎症吸收,值得推广。

大黄附子汤加减方治疗慢性肾衰竭大鼠的疗效机制研究

目的:以Wnt/β-catenin信号通路为切入点,观察大黄附子汤加减方对慢性肾衰竭大鼠一般情况、贫血状况、肾功能、纤维化因子的影响,探讨该方治疗CRF的疗效机制。方法:将80只雄性Wistar大鼠随机选取40只分为空白组、假手术组,其余40只为造模组,并经5/6肾切除术后随机分为模型组、大黄附子汤加减方组。造模完成后4周始,空白组、模型组、假手术组大鼠予生理盐水灌胃,大黄附子汤加减方汤组予大黄附子汤加减方中药液灌胃;治疗后观察各组肾组织病理变化、免疫功能指标及肾功能指标。结果:与空白组比较,模型组大鼠SCr、BUN,以及肾组织Wnt4、β-catenin、TCF1、LEF1、MMP-7表达水平均显著升高(P<0.05),RBC、Hb含量均显著降低(P<0.05)。与模型组比较,大黄附子汤加减方组大鼠SCr、BUN,以及肾组织Wnt4、β-catenin、TCF1、LEF1、MMP-7表达水平均显著降低(P<0.05);RBC和Hb含量显著升高(P<0.05)。结论:大黄附子汤加减方可有效改善CRF大鼠的一般情况、贫血状况、肾脏功能,并能抑制Wnt/β-catnin通路发生活化,下调Wnt4、β-catenin、MMP-7、TCF1、LEF1的表达,减轻肾纤维化程度,延缓CRF病程进展。