该研究旨在阐明黄蜀葵花总黄酮(total flavones of Abelmoschus manihot,TFA)联合恩格列净(empagliflozin,EM)通过调控线粒体稳态和泛凋亡减轻糖尿病肾小管病(diabetic tubulopathy,DT)的作用机制和分子靶点。在体内研究中,首先通过“单肾切除、链脲佐菌素腹腔注射和高脂饲料喂养”建立DT大鼠模型。造模成功后,DT模型鼠分组后分别经灌胃接受TFA、EM、TFA+EM以及生理盐水(安慰剂)连续8周的干预;在体外研究中,使用高糖(high glucose,HG)或分别联合TFA、EM、TFA+EM处理NRK52E细胞或敲低Z-DNA结合蛋白1(Z-DNA binding protein 1,ZBP1)的NRK52E细胞。在体内、外研究中分别观察了肾小管损伤和活性氧(reactive oxygen species,ROS)产物诱导的肾小管上皮细胞损伤的相关特征,分析了肾小管泛凋亡和ZBP1介导的肾小管上皮细胞泛凋亡相关特征,比较了肾脏线粒体裂变标志性分子蛋白表达水平和肾小管上皮细胞线粒体稳态相关特征。此外,在网络药理学研究中,采用HERB数据库和SwissTargetPrediction数据库分别预测并筛选TFA和EM的作用靶点;借助Cytoscape 3.7.2网络图像化软件对筛选出的TFA、EM化学成分及其作用靶点进行相关网络构建;采用OMIM数据库、GeneCards数据库整合DT相关靶点;采用DAVID数据库针对三者交集靶点富集分析基因本体论(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路。体内研究结果显示,TFA+EM能改善DT模型鼠肾小管损伤、肾脏泛凋亡通路关键信号分子蛋白表达水平和表达特征以及肾脏线粒体裂变标志性分子蛋白表达水平,而且,TFA+EM在体内的改善作用均优于TFA或EM;网络药理学的研究结果显示,TFA+EM干预DT可能是通过调控“泛凋亡信号通路”发挥作用;体外研究结果显示,TFA+EM在HG环境下能改善ROS产物诱导的肾小管上皮细胞损伤、ZBP1介导的泛凋亡以及线粒体稳态,包括线�
This article is focused on the changes of electrogastro-activity of rabbits being stimulated at Zusanli with different quality (moxawool vs. tobacco), the quantlty (strong stimulation vs. weak stimulation)and the type (moxasticks vs. moxacones), in order to find the best way to inhibit gastro-hyperactivitycaused by ACh(acetylcholine). The resuh shows that the effects of inhibiting gastro-hyperactivity ofmoxasticks were better than that of tobacco and moxacones, however, the small moxasticks can inhibitthe amplitude of gastro-electricity, the large ones has same effect on amplitude and frequency. From thisexperiment, we know that the effects of moxibustion were interrelated with quality, quantity and thetype of moxibustion
