Guo Xuan, Sun Wen, Xu Guangyuan, Hou Dan, Zhang Zhuo, Wu Lili, Liu Tonghua
Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China.
Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, China.
Evid Based Complement Alternat Med. 2020 Apr 13;2020:8463858. doi: 10.1155/2020/8463858. eCollection 2020.
Diabetes is one of the most serious chronic diseases. Numerous drugs including oral agents and traditional Chinese medicines, such as sitagliptin phosphate (SP) and Fuzhujiangtang granules (FJG), have been discovered to treat diabetes and used in combination in clinical practice. However, the exact effect and underlying mechanism of using combined medicine is not clear. In this study, we compared the antidiabetic effect of SP, FJG, and SP plus FJG (SP-FJG) using forty 8-week-old Zucker diabetic fatty (ZDF) rats and 10 age-matched Zucker lean rats as the normal control group. ZDF rats were treated with different therapies, respectively, for 6 weeks. The study showed that the fast blood glucose, random blood glucose (RBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), homeostasis model of assessment-insulin resistance index, triglyceride (TC), superoxide dismutase, and malondialdehyde of each treatment group were improved when compared with the diabetes mellitus (DM) control group. Using SP-FJG in combination had better improvements in OGTT, fast serum insulin levels, TNF-α, and IL-6 compared with using SP individually. Besides, the increased LDL and TC caused by using SP was attenuated by using FJG in combination. Meanwhile, compared with the DM group, 1781 differentially expressed genes (DEGs) (including 1248 mRNA, 211 ncRNA, 202 cirRNA, and 120 miRNA) were enriched in 58 pathways. Through analysis of ceRNA networks, we found that , , , , and were related to pharmacodynamics in different groups. By analyzing the protein-protein interaction (PPI) and coexpression networks of the transcriptomes of different groups, it is inferred that and may be pharmacodynamic genes for type 2 diabetes mellitus (T2DM). Our research compared the treatment of SP, FJG, and SP-FJG and acquainted the PPI network, coexpression network, mutations, and pharmacodynamics genes, which reveals the new mechanisms of pathogenesis of T2DM.
糖尿病是最严重的慢性疾病之一。已发现包括口服药物和中药在内的多种药物，如磷酸西格列汀（SP）和复方降糖颗粒（FJG），可用于治疗糖尿病并在临床实践中联合使用。然而，联合用药的确切效果和潜在机制尚不清楚。在本研究中，我们以40只8周龄的Zucker糖尿病肥胖（ZDF）大鼠和10只年龄匹配的Zucker瘦大鼠作为正常对照组，比较了SP、FJG以及SP加FJG（SP-FJG）的抗糖尿病作用。ZDF大鼠分别接受不同治疗6周。研究表明，与糖尿病（DM）对照组相比，各治疗组的空腹血糖、随机血糖（RBG）、口服葡萄糖耐量试验（OGTT）、胰岛素耐量试验（ITT）、稳态模型评估-胰岛素抵抗指数、甘油三酯（TC）、超氧化物歧化酶和丙二醛均有改善。与单独使用SP相比，联合使用SP-FJG对OGTT、空腹血清胰岛素水平、TNF-α和IL-6有更好的改善作用。此外，联合使用FJG可减轻SP引起的LDL和TC升高。同时，与DM组相比，1781个差异表达基因（DEGs）（包括1248个mRNA、211个ncRNA、202个cirRNA和120个miRNA）富集于58条通路。通过ceRNA网络分析，我们发现 、 、 、 和 与不同组的药效学相关。通过分析不同组转录组的蛋白质-蛋白质相互作用（PPI）和共表达网络，推测 和 可能是2型糖尿病（T2DM）的药效学基因。我们的研究比较了SP、FJG和SP-FJG的治疗效果，并了解了PPI网络、共表达网络、突变和药效学基因，揭示了T2DM发病机制的新机制。
