基于网络药理学和体外实验探讨黄芪-夏枯草药对治疗糖尿病心肌病的作用机制

目的:基于网络药理学和体外实验探讨黄芪-夏枯草治疗糖尿病心肌病(diabetic cardiomyopathy,DCM)的主要化学成分及其作用机制。方法:运用中药药理学数据库与分析平台获取黄芪-夏枯草药对的主要活性成分及其预测靶点,通过检索GeneCards、OMIM、PharmGkb、DrugBank数据库获得疾病相关基因。筛选出疾病及药物的共同靶点。应用cytoscape3.7.2软件构建“药物-成分-疾病-靶点”的相互作用网络图;运用STRING数据库构建PPI网络。运用R软件将药物-疾病共同靶点进行GO与KEGG功能富集分析,采用Autodock vina 1.1.2进行分子对接。最后通过体外实验验证黄芪-夏枯草含药血清对高糖刺激的心肌细胞的具体机制。将H9c2心肌细胞分为5组:正常组:低糖(5.5 mmol/L)培养;模型组:高糖(33 mmol/L)培养;5%血清组:高糖+5%黄芪-夏枯草药对血清培养;10%血清组:高糖+10%黄芪-夏枯草药对血清培养;15%血清组:HG高糖+15%黄芪-夏枯草药对血清培养。采用MTT法检测细胞存活率,同时采用Western blot检测黄芪-夏枯草含药血清对AKT1、p-AKT1、MAPK14、p-MAPK14蛋白表达的影响。结果:筛选出黄芪-夏枯草31个活性成分,涉及157个DCM靶点及178条相关信号通路。网络分析结果表明黄芪-夏枯草药对可能通过作用AKT1、FOS、MAPK1、MAPK8、MAPK14、JUN等关键靶点及PI3K⁃AKT等关键通路发挥治疗DCM的作用。分子对接提示黄芪-夏枯草药对活性成分木犀草素、槲皮素、毛蕊异黄酮、山柰酚成分与AKT1、MAPK14、MAPK1、FOS、MAPK8、JUN等关键靶点结合性较好,木犀草素与AKT1的Vina得分最低。体外实验结果显示,黄芪-夏枯草含药血清对高糖引起的H9c2心肌细胞的增殖抑制作用有明显改善,并能升高AKT1、MAPK14蛋白的磷酸化水平发挥治疗DCM作用。结论:黄芪-夏枯草治疗DCM具有多靶点、多通路的特点,其机制可能与调控p-AKT1、p-MAPK14的蛋白表达有关。为进一步开展黄芪-夏枯草治疗DCM作用机制研究提供新的思路和依据。

佛香散对糖尿病胃轻瘫大鼠胃动力指标的影响及机制探讨

目的基于动物模型验证佛香散治疗糖尿病胃轻瘫的疗效并探讨可能的作用机制,为治疗糖尿病胃轻瘫提供思路。方法选择50只造模成功的糖尿病胃轻瘫SD大鼠随机分为模型组、西药组及中药高、中、低剂量组,每组10只,中药高、中、低剂量组分别按照浓度为27.5、13.75、6.875 g/(kg·d)佛香散药液灌胃,西药组灌服3.5 mg/(kg·d)多潘立酮溶液,正常组和模型组给予等体积生理盐水灌胃,共8周。比较各组血糖、胃动素、小肠推进率及胃组织病理结构差异。结果正常组血糖显著低于西药组、模型组和中药高、中、低剂量组(P<0.05)。与模型组相比,中药中剂量组和西药组小肠推进率升高(P<0.05);西药组和中药各剂量组胃动素水平明显升高,且中药中剂量组胃动素水平升高最为明显。光镜下观察可见,与模型组胃组织病理结构比较,中药中剂量组胃肌间神经丛神经元数量增多,环形肌和纵行肌增厚,细胞间隙增宽,胞浆无空泡形成,无毛细血管扩张。结论佛香散可促进糖尿病胃轻瘫大鼠胃排空,可能与其提高血清胃动素水平,改善血糖代谢紊乱,并减轻糖尿病胃轻瘫对胃窦的病理损伤,逆转链脲佐菌素致糖尿病大鼠胃组织层的细胞病理损伤有关。

The mechanism of Astragalus-Prunella vulgaris in the treatment of diabetic cardiomyopathy based on network pharmacology and molecular docking

Objective:To study the main chemical components and mechanism of Astragalus and Prunella vulgaris in the treatment of diabetes cardiomyopathy(DCM)based on network pharmacology and in vitro experiments.Methods:The main active components and prediction targets of Astragalus membranaceus and Prunella vulgaris herbal pairs were obtained by TCM Pharmacology database and analysis platform(TCMSP),and the disease genes were retrieved by genecards,OMIM,PharmGKB and drugbank databases.The disease and drug prediction targets were intersected to screen out common potential therapeutic targets.Cytoscape3.7.2 software was used to construct"drug component disease target"interaction network diagram;The PPI network of protein-protein interaction was constructed by using string database.R software was used to analyze the function enrichment of GO and KEGG for drug disease common targets,and autodock Vina 1.1.2 for molecular docking.Finally,the specific mechanism of Astragalus and Prunella vulgaris medicated serum on high glucose stimulated cardiomyocytes was verified in vitro.H9c2 cardiomyocytes were divided into five groups:normal group:low glucose(5.5 mmol/L)culture group,model group:high glucose(33 mmol/L)culture group,5%serum group:high glucose+5%Astragalus membranaceus Prunella vulgaris herb serum culture group,10%serum group:high glucose+10%Astragalus membranaceus Prunella vulgaris herb serum culture group,15%serum group:Hg high glucose+15%Astragalus membranaceus Prunella vulgaris herb serum culture group.MTT assay was used to detect the cell survival rate,and Western blot was used to detect the effect of Astragalus and Prunella vulgaris medicated serum on the expression of AKT1,p-AKT1,MAPK14 and p-MAPK14 proteins.Results:In this study,31 active components of Astragalus and Prunella vulgaris were screened,involving 157 targets of diabetes cardiomyopathy and 178 related signal pathways.The results of network analysis showed that Astragalus and Prunella vulgaris herbs may play a role in the treatment of DCM by acting on key targets such as AKT1,FOS,MAPK1,MAPK8,MAPK14,Jun and key pathways such as PI3K-AKT.Molecular docking showed that Astragalus membranaceus and Prunella vulgaris medicine had good binding between the active components luteolin,quercetin,pistil isoflavone,kaempferol and key targets such as AKT1,MAPK14,MAPK1,FOS,mapk8 and Jun,and the Vina score of luteolin and AKT1 was the lowest.The results in vitro showed that Astragalus and Prunella vulgaris medicated serum significantly improved the inhibition of H9c2 cardiomyocyte proliferation induced by high glucose,and increased the phosphorylation levels of AKT1 and MAPK14 proteins to play a role in the treatment of DCM.Conclusion:Astragalus and Prunella vulgaris have the characteristics of multi-target and multi-channel in the treatment of DCM.Its mechanism may be related to the regulation of the protein expression of p-AKT1 and p-MAPK14.These findings provide a new idea and basis for further experimental study on the mechanism of Astragalus and Prunella vulgaris in the treatment of diabetes cardiomyopathy.

基于贝叶斯网络的航空器机坪运行风险预警

为提高航空器机场安全管理水平,降低机坪运行风险,根据航空器机坪运行特点与规章要求建立风险预警体系。基于质量管理理论,系统识别影响机坪运行安全的各项风险;以航空器机坪运行时间变量为导向构建动态贝叶斯网络模型和算法,评估风险发生的概率,确定机坪风险预警指标权重,建立预警等级。最后,以南京禄口国际机场飞机擦挂事件为例进行预警分析。研究结果表明:通过分析机坪运行风险,构建预警模型可实现对航空器机坪运行的定量评估,从而有针对性地提供预警安全对策,降低事故率。

中药注射剂说明书修订情况分析与思考

依据2006年1月—2020年5月国家药品监督管理局发布的中药注射剂说明书修订公告,对公告涉及的29个品种说明书修订内容进行梳理,分析了中药注射剂说明书存在的问题,为动态修订说明书提供依据。研究发现29个品种说明书修订项目均涉及不良反应、禁忌和注意事项,82.76%增加了警示语,提示说明书修订均为安全性问题。此外说明书尚存在注意事项提及的用药风险33.33%未在不良反应注明,82.76%未注明药物相互作用,17.24%缺乏特殊人群用药,48.28%未注明主治疾病中医证型,44.83%未注明功能主治分型分期,86.21%未注明使用疗程。提示中药注射剂说明书存在药品有效性信息不全面,已知风险显现不完全、缺乏药物相互作用及特殊人群用药、注意事项涉及的风险控制措施需后效评估等问题;提出药品上市许可持有人作为说明书修订的主体,应通过积极开展符合中药特点的上市后基础和临床研究,以中医药理论为指导结合最新研究成果,提高中药注射剂说明书修订水平的同时,为中药注射剂上市后评价提供依据。

《肘后备急方》葱白品种探析

载于《肘后备急方》的葱豉汤是临床治疗风寒表实轻证的常用古方,方中的葱白具有发汗解表,通达阳气的功效,众多医书均有记载。除了用于治疗伤寒表实轻症以外,《肘后备急方》中对于葱的临床运用颇为广泛且具有独到之处,还用于治疗霍乱后卧不安稳、心痛下利无治汗,伤寒后头痛发热,阴阳毒,虚劳病,酒病,脾气亏虚腹痛等症,但关于该书中的葱白是大葱白还是小葱白尚未有关于此方面的研究。该文通过溯源医药古籍有关葱的描述并考证其历史植物形态、葱白性味功效及历代医家临床应用、《肘后备急方》的成书及流行、葱豉汤的水药比以及葱白的化学成分等方面对葱豉汤中葱白的品种来源进行分析,认为《肘后备急方》中葱豉汤的葱白为小葱鳞茎。

糖尿病胃轻瘫的中医治疗思路初探

随着生活水平的提高、糖尿病的发病率逐渐升高,糖尿病胃轻瘫(DGP)已成为影响糖尿病患者身体健康及生活质量的常见并发症。中医药根据辨证论治,采用内治、外治相结合的方法,常可取得较好疗效。文章从中医病因病机学角度阐述中医对DGP的认识和治疗思路,并结合团队前期研究成果,分析DGP中医药研究存在缺少统一的辨证分型标准、客观的疗效评价指标和安全性评价数据等问题,最后提出DGP的研究不仅应统一诊断、辨证及疗效的评价标准,还应建立客观评价指标,注重药物安全性评价,提高临床科研水平,未来还应从多角度深入探讨中医药防治DGP的潜在机制。

Standard Operating Procedures for Chinese Medicine Data Monitoring Committees of Clinical Studies

Although there is guidance from different regulatory agencies,there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee(DMC)for clinical studies of Chinese medicine.We names it as a Chinese Medicine Data Monitoring Committee(CMDMC).A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs.Subsequently,a community standard on CMDMCs(T/CACM 1323-2019)was issued by the China Association of Chinese Medicine on September 12,2019.This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs,which will further develop the scientific integrity and quality of clinical studies.