State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization and The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China.
Hospital of Xinjiang Traditional Uighur Medicine, Urumqi, 830001, China.
Sci Rep. 2019 Mar 13;9(1):4335. doi: 10.1038/s41598-019-40356-5.
The pathogenesis of acute liver injury has been plagued by biologists and physicians. We know little about its therapeutic mechanism. Therefore, this study explored the mechanism of bifendate and muaddil sapra in the treatment of acute liver injury. Firstly, co-expression and cluster analysis of disease-related genes were carried out, and the Go function and KEGG pathway of modules and related genes were identified. Secondly, pivot analysis of modules can identify key regulators. On the other hand, based on the acute liver injury induced by CCl4, we use the combined analysis of proteomics and transcriptome to find therapeutic targets and related mechanisms of drugs. A total of 21 dysfunction modules were obtained, which were significantly involved in immune system, hepatitis and other related functions and pathways. Transcriptome analysis showed 117 targets for bifendate treatment, while 119 for muaddil sapra. Through exploring the mechanism, we found that the two drugs could modulate the module genes. Moreover, bifendate regulate the dysfunction module through ncRNA (SNORD43 and RNU11). Muaddil sapra can mediate dysfunction modules not only by regulating ncRNA (PRIM2 and PIP5K1B), but also by regulating TF (STAT1 and IRF8), thus having a wider therapeutic potential. On the other hand, proteome analysis showed that bifendate mainly regulated Rac2, Fermt3 and Plg, while muaddil sapra mainly regulated Sqle and Stat1. In addition, muaddil sapra regulates less metabolic related proteins to make them more effective. Overall, this study not only provides basic theory for further study of the complex pathogenesis of acute liver injury, but also provides valuable reference for clinical use of bifendate and muaddil sapra in the treatment of acute liver injury.
急性肝损伤的发病机制一直困扰着生物学家和医生。我们对其治疗机制知之甚少。因此，本研究探讨了双飞粉和 muaddil sapra 治疗急性肝损伤的机制。首先，进行疾病相关基因的共表达和聚类分析，鉴定模块和相关基因的 GO 功能和 KEGG 通路。其次，对模块进行枢纽分析，可以识别关键调节剂。另一方面，基于 CCl4 诱导的急性肝损伤，我们结合蛋白质组学和转录组学分析，寻找药物的治疗靶点和相关机制。共获得 21 个功能失调模块，它们显著参与免疫系统、肝炎等相关功能和途径。转录组分析显示，双飞粉治疗的靶点有 117 个，muaddil sapra 则有 119 个。通过探讨机制，我们发现两种药物可以调节模块基因。此外，双飞粉通过 ncRNA（SNORD43 和 RNU11）调节功能失调模块。Muaddil sapra 不仅可以通过调节 ncRNA（PRIM2 和 PIP5K1B），还可以通过调节 TF（STAT1 和 IRF8）来调节功能失调模块，从而具有更广泛的治疗潜力。另一方面，蛋白质组分析表明，双飞粉主要调节 Rac2、Fermt3 和 Plg，而 muaddil sapra 主要调节 Sqle 和 Stat1。此外，muaddil sapra 调节较少的代谢相关蛋白，使其更有效。总之，本研究不仅为进一步研究急性肝损伤复杂发病机制提供了基础理论，也为双飞粉和 muaddil sapra 临床治疗急性肝损伤提供了有价值的参考。
