In vivo evaluation and mechanism prediction of anti-diabetic foot ulcer based on component analysis of Ruyi Jinhuang powder

BACKGROUND Diabetes is a metabolic disease with a high complication rate.Diabetic foot ulcers(DFUs)seriously affect the quality of life of patients.A total of 15%-20%of diabetic patients develop DFUs,which heal with difficulty over a long time and can result in amputation and disability.Traditional Chinese medicine has a unique effect in the treatment of skin ulcerative diseases.Ruyi Jinhuang powder(RHP)is one of the classic prescriptions in traditional Chinese medicine and is widely used in clinical practice.AIM To verify the ability of RHP to promote wound healing by electron microscopy analysis in animal models and hematoxylin-eosin(HE)staining.The effective components of RHP were extracted and identified by gas chromatography-mass spectrometry(GC-MS),and the obtained chemical components were analyzed by network pharmacology methods to predict its therapeutic mechanism.METHODS Sprague Dawley rats were injected with streptozotocin to establish the DFU model.HE staining was used to observe the wound tissue under an electron microscope.The chemical constituents of RHP were extracted first by supercritical fluid extraction and alcohol extraction,and then,GC-MS and ultra-performance liquid chromatography–MS were used to separately identify the chemical constituents.In addition,the"herb-component-target"link was established through the Traditional Chinese Medicine Systems Pharmacology database to obtain the target information,and the molecular docking of important components and key targets was performed in Discovery Studio software.Cytoscape software was used to visualize and analyze the relationship between the chemical composition,targets and Traditional Chinese Medicine network.RESULTS RHP promoted DFU healing in rats by affecting fibroblasts and nerve cells.A total of 89 chemical components were obtained by GC-MS.Network pharmacological analysis revealed that RHP was associated with 36 targets and 27 pathways in the treatment of DFU,of which the important components were luteolin,trans caryophyllene,ar-turmerone,palmitic acid,methyl palmitate,gallic acid,demethoxycurcumin,berberine,and rheic acid.The key targets were posttranscriptional silencing,topoisomerase II alpha,muscarinic acetylcholine receptor M2,interleukin 6,tumor necrosis factor and retinoic X receptor alpha,and the key pathways were the phosphoinositide 3-kinase-protein kinase B signaling pathway,neuroactive ligand–receptor interactions,and the forkhead box O signaling pathway.CONCLUSION Our results indicated that RHP may play a role in the treatment of DFU through these target pathways by affecting insulin resistance,altering the nervous system and immune system,participating in inflammatory responses and regulating cell proliferation,differentiation and apoptosis through other specific mechanisms.

Jinhuang powder for the treatment of diabetic foot ulcers:an updated metaanalysis with power analysis and trial sequential analysis

Background:Traditional Chinese Medicines(TCM)had been indicated to benefit for the chronic non-infectious diseases,such as cancers,hypertension,primary dysmenorrheal,etc.Although randomized controlled trials(RCTs)had been conducted,there was still the controversy on the efficacy of Jinhuang powder for diabetic foot ulcers(DFUs).Objective:This systematic review aimed to objectively evaluate the potential of Jinhuang powder for DFUs.Methods:Seven databases(CNKI,Chongqing VIP,Wanfang database,CBM,the Cochrane Library,PubMed and Web of Science)were searched to retrieve RCTs up to December,2016;and the relevant references of the eligible studies were screened.According to the eligible criteria,the literature was screened;data were extracted;and then the methodological quality was assessed.The meta-analysis,power analysis and trial sequential analysis(TSA)were performed by using Meta analyst software(version beta 3.13),Stata 12.0,Power and Precision statistical software package(Biostat)and TSA software(version0.9),respectively.Results:Finally,three RCTs with 198 participants were included.The results of meta-analysis showed that there were statistically significant differences between groups in(1)the cure rate(RR,1.25;95%CI.1.10to1.41;P=0.00)and(2)the wound healing time(SMD,-3.404;95%CI,-5.821 to -0.987;P=0.00).Three trials presented more than 80% power with 0.05α-errors in both outcomes and the power of two meta-analyses to pool different outcomes presented more than 95%.The TSA showed that the summary results were certain.Conclusion:The external application with Jinhuang powder was an effective and cost-effective therapy for DFUs.The power analysis and TSA showed that the efficacy of Jinhuang powder dressing for the treatment of DFUs is conclusive.

Effect of bifidobacterium triple viable powder adjuvant therapy on the inflammatory factors and t lymphocytes subsets in patients with ulcerative colitis

Objective:To investigate effect of bifidobacterium triple viable powder on inflammatory factors and T lymphocyte subsets in patients with ulcerative colitis.Method:80 patients with ulcerative colitis were selected and divided into observation group and control group, 40 cases in each group. The control group was given dietary guide, mesalazine, vitamin C and other comprehensive treatment;The observation group was given bifidobacterium triple viable powder adjuvant therapy on the basis of conventional treatment. The level of IL-6, CRP, TNF-α and T lymphocyte subsets in the two groups was compared before treatment (T0), after treatment for 1 month (T1), after treatment for 3 months (T2).Results: (1) The levels of IL-6, CRP and TNF-α at T1 serum were lower than those in T0 in both groups, the levels of serum IL-6, CRP and TNF-α at T2 were lower than those of T0 and T1, these three levels in different time points were statistical significant difference;The levels of serum IL-6, CRP and TNF-α in observation group at T1 and T2 were significantly lower than those in control group, there was significant difference in both groups;(2)The levels of CD3+, CD4+, CD4+/CD8+ at T1 were higher than T0 in two groups, The levels of CD3+, CD4+, CD4+/CD8+ at T2 were superior than at T0 and T1. The level of CD8+ at T1 was below at T0, The level of CD8+ at T2 was inferior than those in T0 and T1, The levels of CD3+,CD4+,CD8+ and CD4+/CD8+ at different time points were significant difference. The levels of CD3+, CD4+, CD4+ /CD8+ in the observation group were significantly higher than those in the control group T1 and T2, CD8+ level was significantly lower than that in the control group at T1 and T2, difference between the two groups was statistically significant.Conclusion:Bifidobacterium triple viable powder adjuvant treatment ulcerative colitis was good for inhibiting body inflammatory response and improve immune function.

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.

Therapeutic Effect and Mechanism of New Maixian Powder on DSS-induced UC Rats

[Objectives] To study the therapeutic effect and mechanism of New Maixian Powder on ulcerative colitis( UC) rats through observing its regulatory effect on the protein kinase R-like endoplasmic reticulum kinase( PERK)/eukaryotic translation initiation factor-2α( e IF-2α)/nuclear transcription factor-kappa B( NF-κB) signaling pathway. [Methods]First,60 SD rats were randomly divided into normal group,model group,mesalazine group,and New Maixian Powder low,medium and high dose groups,10 rats each group. Then,dextran sulfate sodium( DSS) was used to induce UC rats. The mesalazine group was given 0. 42 g/( kg·d) of mesalazine sustained-release granule suspension,New Maixian Powder low,medium and high dose groups were given 1. 5,3,and 6 g/( kg·d) of New Maixian Powder suspension,respectively,and other groups were given an equal volume of physiological saline,continuous intragastric administration for 14 d. Next,the disease activity index( DAI) of UC rats was evaluated; the expression of NF-κB in serum was measured by enzyme-linked immunosorbent assay( ELISA); the expression of PERK and e IF-2α protein and m RNA in colon tissue was detected by Western blot and real-time quantitative polymerase chain reaction( RT q-PCR). [Results] Compared with the normal group,the DAI score and serum NF-κB level in the model group were significantly higher( P < 0. 05),and PERK and e IF-2α protein and m RNA levels in the colon tissue were increased( P < 0. 05); compared with the model group,the DAI score decreased and serum NF-κB level declined in the New Maixian Powder group,and the expression of PERK and e IF-2α protein and m RNA in New Maixian Powder medium dose and high dose groups declined( P < 0. 05). [Conclusions]New Maixian Powder has good therapeutic effect on UC rats,and its mechanism may be connected with the inhibition of the activation of PERK/e IF-2α/NF-κB signaling pathway.

Efficacy of compound Bai Yu San in treating diabetic skin ulcer

Objective:To assess the efficacy of compound Bai Yu San(CBYS)as a new treatment option,in healing diabetic skin ulcer.Materials and Methods:A total of 64 diabetic patients with skin ulcer were enrolled and randomly assigned to experimental group(n=33)and control group(n=31).In the control group,normal saline(NS)was used to cleanse the wound.After debridement,the wound was dressed with modern materials.In the experimental group,the NS‑cleansed wound was dressed with CBYS.The infection rate,healing rate,treatment cost,and patient satisfaction between the two groups were compared.Results:On the 35th day after treatment,the infection rate and healing rate showed no between‑group difference(P>0.05);the experimental group showed lower treatment cost and higher satisfaction than the control group(P<0.05).Conclusion:As a new treatment option for diabetes‑induced skin ulcer,CBYS can effectively control the infection,promote the healing,reduce treatment cost,and increase patient satisfaction.Dressing with CBYS can be clinically replicated in the treatment of diabetic skin ulcer.

Research progress of compound Baiyu powder in treatment of chronic refractory wounds

Chronic refractory w ounds are common and frequently-seen diseases in surgery.Due to their long course of disease and complex pathogeneses,chronic refractory w ounds arouse high attention in clinic.With the preliminary results of clinical research of their pathogeneses and new treatments achieved,traditional Chinese medicine(TCM),w ith its unique concept,breaks the limitation commonly existing in the methods of w estern medicine,especially obtaining certain achievements in chronic refractory w ounds.This paper review ed the therapeutic effects of compound Baiyu pow der in the treatment of chronic refractory w ounds to prove to be effective,convenient to use and save medical costs.

健脾益肠散对溃疡性结肠炎大鼠NLRP3信号通路IL-1β、IL-18表达的影响

目的探讨健脾益肠散对溃疡性结肠炎(UC)模型大鼠NLRP3信号通路白细胞介素(IL)-1β、IL-18表达的影响。方法从40只SD大鼠随机选取10只作为正常组,其余大鼠自由饮用5%硫酸葡聚糖溶液7 d制备UC大鼠模型,将成模大鼠随机分为模型组、柳氮磺吡啶组和健脾益肠散组,每组10只。健脾益肠散组和柳氮磺吡啶组予相应药液灌胃,正常组和模型组予等体积蒸馏水灌胃,连续14 d。观察大鼠一般状况,并进行疾病活动指数(DAI)评分,ELISA检测大鼠血清核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶1(Caspase-l)含量,免疫组化染色、Western blot和RT-PCR检测结肠组织IL-1β、IL-18蛋白及mRNA表达。结果与正常组比较,模型组大鼠一般状况较差,DAI评分显著升高(P<0.01),血清NLRP3、ASC、Caspase-l含量显著增加(P<0.01),结肠组织IL-1β、IL-18蛋白和mRNA表达均显著升高(P<0.01);与模型组比较,健脾益肠散组和柳氮磺嘧啶组大鼠一般状况明显好转,DAI评分显著降低(P<0.01),血清NLRP3、ASC、Caspase-l含量明显减少(P<0.05,P<0.01),结肠组织IL-1β、IL-18蛋白和mRNA表达均明显降低(P<0.05,P<0.01)。结论健脾益肠散可抑制NLRP3信号通路IL-1β、IL-18表达,改善结肠免疫炎症损伤,发挥治疗UC作用。

健脾益肠散对TNF-α诱导的树突状细胞NLRP3炎症小体信号通路表达的影响

目的观察健脾益肠散对肿瘤坏死因子-α(TNF-α)诱导的树突状细胞(DCs)NLRP3炎症小体信号通路相关蛋白表达的影响,探讨其治疗溃疡性结肠炎的作用机制。方法分离培养C57BL/6小鼠原代DCs,分为正常组、模型组、阴性对照组、阳性药组和中药组,TNF-α诱导构建DCs炎症微环境模型,各组分别予相应处理后,采用CCK-8法检测细胞增殖能力,免疫荧光、Western blot分别检测DCs核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶-1(Caspase-1)蛋白表达,Western blot、RT-PCR分别检测DCs白细胞介素(IL)-1β、IL-18蛋白和mRNA表达。结果与正常组比较,模型组DCs增殖能力显著下降(P<0.01),细胞NLRP3、ASC、Caspase-1阳性表达显著升高,NLRP3、ASC、Caspase-1、IL-18、IL-1β蛋白表达及IL-18、IL-1βmRNA表达显著升高(P<0.01);与模型组和阴性对照组比较,阳性药组和中药组DCs增殖能力显著上升(P<0.01),细胞NLRP3、ASC、Caspase-1阳性表达显著降低(P<0.01),NLRP3、ASC、Caspase-1、IL-1β、IL-18蛋白表达显著降低(P<0.05,P<0.01),IL-1β、IL-18mRNA表达显著降低(P<0.01),且中药组细胞增殖能力、Caspase-1阳性表达、IL-18 mRNA表达均明显高于阳性药组(P<0.05),IL-1βmRNA表达明显低于阳性药组(P<0.05)。结论健脾益肠散能抑制TNF-α诱导的DCs炎性反应,其治疗溃疡性结肠炎作用机制可能与调控NLRP3炎症小体信号通路NLRP3、ASC、Caspase-1、IL-18、IL-1β表达有关。

冰硼散联合牛黄上清胶囊和维生素B2治疗复发性口腔溃疡的临床效果研究

目的探讨冰硼散联合牛黄上清胶囊和维生素B2治疗复发性口腔溃疡的临床效果。方法选取36例复发性口腔溃疡患者,通过抽签法分为观察组和对照组,每组18例。对照组仅使用冰硼散进行治疗,观察组在对照组基础上增加牛黄上清胶囊和维生素B2治疗。比较两组患者的临床治疗效果及复发情况。结果观察组治疗总有效率94.4%明显高于对照组的66.7%,差异有统计学意义(P<0.05)。两组均未见不良反应。两组随访1、3、6个月的复发率无显著差异(P>0.05);但观察组总复发率22.2%显著低于对照组的61.1%,差异有统计学意义(P<0.05)。结论冰硼散联合牛黄上清胶囊和维生素B2治疗复发性口腔溃疡可有效缓解溃疡疼痛症状,促进溃疡愈合,并降低溃疡复发率,具有较好的临床治疗效果。

基于自噬探讨健脾益肠散对溃疡性结肠炎模型大鼠肠黏膜保护的作用机制

目的通过观察健脾益肠散对溃疡性结肠炎模型大鼠结肠自噬相关分子表达的影响,探讨其肠黏膜保护的作用机制。方法将SD大鼠随机分为正常组、模型组、健脾益肠散组和柳氮磺吡啶组。采用2,4,6-三硝基苯磺酸(TNBS)-乙醇溶液复合法建立溃疡性结肠炎大鼠模型;模型复制成功后灌胃给药,每日1次,持续14 d。观察大鼠一般状况,计算疾病活动指数(DAI)评分;苏木素-伊红(HE)染色法观察结肠组织病理形态;透射电镜观察结肠上皮细胞自噬情况;免疫荧光染色法、蛋白免疫印迹法(Western Blot)检测结肠组织肌球蛋白样BCL2结合蛋白(Beclin1)、微管相关蛋白1轻链3(LC3)蛋白表达;实时荧光定量聚合酶链反应(Real-time PCR)检测自噬蛋白5(Atg5)、自噬蛋白7(Atg7)、泛素结合蛋白62(p62)mRNA表达。结果与正常组比较,模型组一般情况较差,DAI评分明显升高(P<0.0001);结肠组织出现明显的上皮细胞损伤,电镜下自噬体的数量明显减少;结肠组织Beclin1、LC3-II/LC3-I蛋白及Atg5、Atg7 mRNA表达明显降低(P<0.0001),p62 mRNA表达明显升高(P<0.0001)。与模型组比较,健脾益肠散组大鼠一般情况明显恢复,DAI评分明显降低(P<0.0001);结肠组织病理损伤有不同程度的改善,电镜下自噬体的数量明显增多;结肠组织Beclin1、LC3-II/LC3-I蛋白及Atg5、Atg7 mRNA表达明显升高(P<0.01,P<0.001,P<0.0001),p62 mRNA表达明显降低(P<0.01)。结论健脾益肠散可通过上调自噬相关分子Beclin1、LC3、Atg5及Atg7的表达,下调p62的表达,增强自噬以达到保护溃疡性结肠炎模型大鼠结肠黏膜损伤的作用。

参苓白术散药味增减对溃疡性结肠炎模型小鼠的治疗效果

为了探寻参苓白术散药味增减对葡聚糖硫酸钠诱导的溃疡性结肠炎小鼠的治疗效果,试验将30只雌性C57BL/6小鼠(6~8周龄,体重为18~20 g)随机分成5组,分别为空白对照组、模型组及高、中、低剂量组,每组6只。第1周各组适应性饲养;第2周除空白对照组外,每组用3%葡聚糖硫酸钠水溶液自由饮水,连用7 d,建立急性溃疡性结肠炎模型;第3周更换正常饮水,空白对照组和模型组灌胃生理盐水,高、中、低剂量组按体重分别灌胃0.2,0.1,0.05 mL/10 g中药药液。观察并记录小鼠临床症状,采集全血分离血清,检测血清中免疫球蛋白G(IgG)、免疫球蛋白A(IgA)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)、二胺氧化酶(DAO)、D-乳酸的质量浓度,同时制作小鼠结肠组织病理切片。结果表明:与空白对照组比较,模型组血清中IL-8、IgA、IgG、DAO、D-乳酸的质量浓度极显著升高(P<0.01),IL-10的质量浓度极显著降低(P<0.01);给药后,高、中、低剂量组小鼠的炎症均有不同程度缓解,IL-8、IgA、IgG、DAO、D-乳酸的质量浓度均有不同程度下降,IL-10的质量浓度上升。说明参苓白术散药味增减对葡聚糖硫酸钠诱导的溃疡性结肠炎有良好的治疗作用,在本试验条件下,按体重0.2 mL/10 g给药治疗效果最好。

董筠基于甘淡益阴法论治溃疡性结肠炎经验

介绍董筠教授基于甘淡益阴法论治溃疡性结肠炎临床经验。溃疡性结肠炎(ulcerative colitis,UC)是一种结直肠慢性炎症性疾病,近年来该病已逐渐成为临床常见消化系统疾病,病情反复,迁延难愈,给患者及其家庭带来严重的物质与精神负担,被列为疑难杂症。中医常将UC归属于“久痢”范畴,董筠教授长期从事于中西医结合论治溃疡性结肠炎,认为本病病程迁延,反复难愈,发展至疾病后期常可见虚实夹杂证,以湿热为标,阴虚或气阴两虚为本。探究其成因,董师认为脾阴虚的形成常与饮食失节、劳倦失度、情志内伤、病程日久暗耗脾阴相关。故治疗本病之时,董师主张基于甘淡益阴大法,益阴健脾,补泻兼施,滋阴和阳,佐以清热利湿、理气通腑、去滞和血之品,以和为贵,如此则湿热祛,阴血生,脾运健,气血和,中焦复常。临证以六神散为代表方加减论治溃疡性结肠炎见脾阴虚诸症者常获良效,附验案一则。此外,董师注重本病日常宣教、慢病管理,缓后防复,亦获佳效。

健脾益肠散对TNF-α处理树突状细胞炎症因子水平及共刺激分子CD40表达的影响

目的:观察健脾益肠散对肿瘤坏死因子α(TNF-α)处理的树突状细胞(DC)炎症因子水平及其刺激分子CD40表达的影响。方法:原代分离、培养C57BL/6小鼠DC细胞,采用流式细胞术对DC的主要标记物CD11c进行鉴定,并将培养的DCs随机分为正常组、模型组、阴性对照组、阳性药组及受试药组,TNF-α处理细胞构建DC炎症微环境模型,各组给予不同处理后,于倒置荧光显微镜下观察各组DCs的形态,采用CCK-8检测细胞的增殖能力,采用ELISA法检测各组DC培养上清液中CD40、IL-1β及IL-18含量,采用Western blot及RT-PCR技术分别检测各组DCs中CD40的蛋白和mRNA表达水平。结果:分离纯化的DC的CD11c表达率为85.1%,与正常组比较,模型组DC培养上清液中CD40、IL-1β及IL-18的含量、细胞中CD40的蛋白及其mRNA表达均明显增多,而增殖能力显著下降(P<0.01);受试药组DC培养上清液中CD40、IL-1β及IL-18的含量、CD40的蛋白及其mRNA表达减少,且细胞增殖能力上升,与模型组及阴性对照组相比较皆有统计学意义(P<0.01)。结论:健脾益肠散对TNF-α处理的DCs共刺激分子CD40的蛋白和mRNA表达及炎症因子的含量具有明显的抑制作用,可能是其发挥免疫耐受作用治疗溃疡性结肠炎的重要机制之一。

鹳榆止泻散防治猪溃疡性结肠炎的潜在作用机制

采用网络药理学和分子对接技术探究自拟中药组方鹳榆止泻散防治猪溃疡性结肠炎(PUC)的作用靶点及机制.通过中药系统药理学数据库与分析平台(TCMSP)筛选鹳榆止泻散中5种药物活性成分及靶点,基于PUC相关疾病数据库(GeneCards,OMIM,PharmGkb,TTD,DrugBank)综合检索疾病相关靶点,Venn可视化两者共同关键靶点.采用STRING平台构建潜在靶点蛋白互作(PPI)网络,Cytoscape 3.8.0软件对关键靶点进行网络拓扑学分析及核心基因提取,同时建立鹳榆止泻散“活性成分-潜在作用靶点”网络,并对所得的核心基因进行基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析,预测鹳榆止泻散治疗PUC的分子机制,最后通过Autodock软件进行结合位点和分子对接验证.通过数据分析得出鹳榆止泻散治疗PUC可能与槲皮素、苦参碱、山奈酚、β-谷甾醇、柚皮素、木犀草素、甘草异黄酮等化学成分有关,筛选出fos,jun,rela,esr1,mapk1等为核心靶点,富集分析得到GO条目2 461条,KEGG通路176条,主要涉及炎症信号通路和PI3K/Akt信号通路等,分子对接结果显示关键活性成分与对应靶点具有较好的结合活性.结果表明:鹳榆止泻散中活性成分通过干预fos,jun,rela,esr1,mapk1等关键靶点,调节多条信号通路,抑制炎症反应,发挥防治猪溃疡性结肠炎的效果.

三七白及散调节PI3K/AKT信号通路对血瘀型胃溃疡大鼠胃黏膜损伤的影响

目的探讨三七白及散调节磷酸肌醇3激酶(PI3K)/蛋白激酶B(AKT)信号通路对血瘀型胃溃疡(Gastric ulcer,GU)大鼠胃黏膜损伤的影响。方法将50只SPF级健康SD大鼠按随机数字表法分为对照组、模型组、三七白及散低剂量(1.16 g/kg)组、三七白及散高剂量(2.32 g/kg)组、三七白及散高剂量(2.32 g/kg)+740Y-P(PI3K激活剂,10 mg/kg)组,每组各10只,模型组与给药组大鼠采用冷暴露+灌胃盐酸乙醇溶液法构建血瘀型GU模型,以三七白及散与740Y-P分组干预治疗后检测大鼠胃溃疡面积、溃疡指数(Ulcer index,UI)与胃黏膜血流(Gastric mucosal blood flow,GMBF);检测大鼠血液流变学指标全血高切黏度、全血中切黏度、全血低切黏度与血浆黏度;HE染色检测大鼠胃黏膜组织病理形态;ELISA测定大鼠血清促炎因子白细胞介素-6(Interleukin-6,IL-6)、前列腺E2(Prostaglandin E2,PGE2)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)水平;用试剂盒检测大鼠胃黏膜组织氧化应激因子谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)、超氧化物歧化酶(Superoxide dismutase,SOD)、丙二醛(Malondialdehyde,MDA)水平;免疫印迹法检测大鼠胃黏膜组织PI3K/AKT通路相关蛋白表达。结果与对照组比较,模型组大鼠胃黏膜组织有明显病理损伤,胃溃疡面积与UI、全血高切黏度、全血中切黏度、全血低切黏度与血浆黏度、血清IL-6、PGE2与TNF-α水平、胃黏膜组织MDA水平与p-PI3K/PI3K、p-AKT/AKT明显升高(P<0.05),GMBF、胃黏膜组织GSH-Px、SOD水平明显降低(P<0.05)。与模型组比较,三七白及散低、高剂量组大鼠胃黏膜组织病理损伤均减轻,胃溃疡面积与UI、全血高切黏度、全血中切黏度、全血低切黏度与血浆黏度、血清IL-6、PGE2与TNF-α水平、胃黏膜组织MDA水平与p-PI3K/PI3K、p-AKT/AKT均降低(P<0.05),GMBF、胃黏膜组织GSH-Px、SOD水平均升高(P<0.05)。与三七白及散低剂量组比较,三七白及散高剂量组大鼠胃溃疡面积与UI、全血高切黏度、全血中切黏度、全血低切黏度与血浆黏度、血清IL-6、PGE2与TNF-α水平、胃黏膜组织MDA水平与p-PI3K/PI3K、p-AKT/AKT进一步降低(P<0.05),GMBF、胃黏膜组织GSH-Px、SOD水平进一步升高(P<0.05)。与三七白及散高剂量组比较,三七白及散高剂量+740Y-P组大鼠胃溃疡面积与UI、全血高切黏度、全血中切黏度、全血低切黏度与血浆黏度、血清IL-6、PGE2与TNF-α水平、胃黏膜组织MDA水平与p-PI3K/PI3K、p-AKT/AKT升高(P<0.05),GMBF、胃黏膜组织GSH-Px、SOD水平降低(P<0.05)。结论三七白及散可通过抑制PI3K/AKT信号通路激活而减轻血瘀型GU大鼠炎症与氧化应激,改善其血液流变学指标与胃黏膜血液循环,进而减轻大鼠胃黏膜损伤。

基于氧化应激反应探讨慢性体表溃疡发病机理及象皮生肌膏联合托里消毒散的干预作用

目的 探讨慢性体表溃疡发病机理以及象皮生肌膏联合托里消毒散的干预作用。方法 将30只SPF级雄性SD大鼠按随机数字表法分为空白对照组、模型组、象皮生肌膏组、托里消毒散组、象皮生肌膏联合托里消毒散组,每组各6只。采用金黄色葡萄球菌造模,连续给药1周后,检测创面组织中血管内皮生长因子(Vascular endothelial growth factor,VEGF)、血管内皮细胞生长因子受体2(Vascular endothelial growth factor receptor 2,VEGFR-2)、核因子E2相关因子2(Nuclear factor erythroid 2-related factor 2,Nrf2)、NAD(P)H醌氧化还原酶1[NAD(P)H quinone oxidoreductase1,NQO1)、血红素加氧酶1(Heme oxygenase-1,HO-1)]表达水平。结果 与空白对照组比较,模型组创面组织中VEGF、VEGFR-2表达均明显降低,差异有统计学意义(P<0.01);与模型组比较,象皮生肌膏组、托里消毒散组、象皮生肌膏联合托里消毒散组VEGF、VEGFR-2表达均明显升高,差异有统计学意义(P<0.01)。与对照组比较,模型组中Nrf2、NQO1、HO-1表达水平升高,差异有统计学意义(P<0.01);与模型组比较,象皮生肌膏组、托里消毒散组、象皮生肌膏联合托里消毒散组Nrf2表达水平均明显升高,NQO1和HO-1表达降低,差异有统计学意义(P<0.01)。结论 大鼠慢性溃疡的形成可能与氧化应激反应抑制了VEGF通路及Nrf2通路有关,而象皮生肌膏联合托里消毒散可能通过调节上述通路促进溃疡处血管新生和抗氧化应激,进而提高创面愈合能力。

针刺联合参苓白术散调控Nrf2/HO-1通路对溃疡性结肠炎大鼠炎症及氧化应激反应的影响

目的观察针刺联合参苓白术散正调控核因子相关因子2(Nuclear factor erythroid 2related factor 2,Nrf2)/血红素加氧酶-1(Heme oxygenase-1,HO-1)通路对溃疡性结肠炎(Ulcerative colitis,UC)大鼠炎症及氧化应激反应的影响。方法将60只SPF级健康雄性SD大鼠分为对照组10只和造模组50只,对照组不做特殊处理,造模组采用TNBS/乙醇灌肠法进行UC造模,造模成功后采用随机数字表法分为模型组、针刺组、参苓白术散组、联合组和西药组,每组各10只。治疗14 d后,评价疾病活动指数(Disease activity index,DAI)和结肠大体形态损伤指数(Colon macroscopic damage index,CMDI),检测肠黏膜组织中肿瘤坏死因子(Tumor necrosis factor-α,TNF-α)、白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-18(Interleukin-18,IL-18)、活性氧簇(Reactive oxygen species,ROS)、丙二醛(Malondialdehyde,MDA)、超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)的含量及Nrf2、HO-1的表达水平。结果模型组大鼠的DAI、CMDI、肠黏膜组织中TNF-α、IL-1β、IL-6、IL-18、ROS、MDA的含量高于对照组,肠黏膜组织中GSH-Px、SOD的含量及Nrf2、HO-1的表达水平低于对照组,差异有统计学意义(P<0.05);针刺组、参苓白术散组、联合组和西药组大鼠的DAI、CMDI、肠黏膜组织中TNF-α、IL-1β、IL-6、IL-18、ROS、MDA的含量低于模型组,肠黏膜组织中GSH-Px、SOD的含量及Nrf2、HO-1的表达水平模型组,差异有统计学意义(P<0.05),且联合治疗组的上述改善较针刺组、参苓白术散组、西药组更为明显,差异有统计学意义(P<0.05)。结论针刺联合参苓白术散改善UC大鼠的炎症及氧化应激,其作用机制可能与正调控Nrf2/HO-1通路有关。

参苓白术散联合肠愈灌肠方治疗活动期溃疡性结肠炎疗效观察

目的:观察中药参苓白术散内服联合肠愈灌肠方保留灌肠对活动期溃疡性结肠炎的疗效。方法:选取符合标准的安徽省中医院肛肠科收治的70例活动期溃疡性结肠炎患者,随机分为观察组(35例)、对照组(35例)。观察组运用参苓白术散内服配合肠愈灌肠方保留灌肠,内服中药每早晚各200mL温服;灌肠中药每晚睡前灌肠1次。对照组则选用美沙拉嗪栓1粒每晚纳肛,分别比较治疗前和治疗30天后2组的临床疗效、中医症候积分(腹泻、腹痛、脓血便、里急后重)、肠镜Baron评分以及炎症因子[C反应蛋白(CRP)、降钙素原(PCT)]水平。结果:观察组临床总有效率94.29%,远高于对照组的80%(P<0.05);2组治疗后肠镜Baron评分均低于治疗前,且观察组低于对照组(P<0.05);2组治疗后中医症候积分均低于治疗前,且观察组低于对照组(P<0.05);2组治疗后CRP、PCT水平均低于治疗前,且观察组低于对照组(P<0.05)。结论:参苓白术散联合肠愈灌肠方治疗活动期溃疡性结肠炎具有确切的效果,可提高临床治疗有效率,其机制可能与抑制炎症反应、快速促进结肠黏膜恢复有关,且具有良好的安全性。

加味导赤散联合沙利度胺片治疗心脾积热型复发性阿弗他溃疡的疗效评价

目的:研究加味导赤散联合沙利度胺片治疗心脾积热型复发性阿弗他溃疡的疗效。方法:在本文研究将2022年1月—2023年6月上海中医药大学附属普陀医院收治的88例心脾积热型复发性阿弗他溃疡患者作为研究主要对象,随机分组为两组,各44例,对照组实施沙利度胺片治疗,观察组实施加味导赤散联合沙利度胺片治疗,分析并对比两组发作间歇时间、总有效率、溃疡复发率、炎症因子水平。结果:观察组发作间歇时间优于对照组,差异有统计学意义(P<0.05);观察组治疗4周的总有效率高于对照组,差异有统计学意义(P<0.05);观察组溃疡复发率低于对照组,差异有统计学意义(P<0.05);观察组治疗后炎症因子低于对照组,差异有统计学意义(P<0.05)。结论:通过对心脾积热型复发性阿弗他溃疡患者开展联合治疗(加味导赤散、沙利度胺片),能显著提高疗效。