Ghanbari Mahboubeh, Ebrahimi Hossein, Bagheri Abouzar, Khonakdar-Tarsi Abbas, Mousavi Hadis
Molecular and Cell biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Cell Biochem Biophys. 2025 Apr 17. doi: 10.1007/s12013-025-01751-0.
This study aims to investigate the impact of silibinin (SILI) on the expression of the Lipin-1 and Lipin-2 genes during warm ischemia-reperfusion (I/R) of the liver. Network pharmacology was employed to identify potential targets of SILI in the context of liver inflammation and to elucidate the mechanism underlying the regulation of Lipin gene expression. The rats were allocated into four groups, each comprising eight individuals: vehicle group: These rats underwent a median laparotomy, and were administered normal saline. (2) SILI group: Rats in this group received 50 mg/kg of SILI after laparotomy. (3) I/R group: Rats in this group experienced I/R and were administered normal saline. (4) I/R+SILI group: In this group, rats were treated with SILI in conjunction with the I/R procedure. Western and real-time PCR were used to measure protein levels, and assess Lipin-1 and Lipin-2 gene expression. The analysis identified 18 shared targets between SILI (Severe Acute Liver Injury) and liver inflammation, linking them to 107 KEGG pathways, with the mTOR signaling pathway standing out as a critical connection to Lipin. Docking studies of targets in the mTOR signaling pathway revealed binding energies of -9.7 kcal/mol for PIK3CA and -10.4 kcal/mol for mTOR protein. Furthermore, the protein level and gene expression of Lipin-1 and Lipin-2 genes were significantly elevated during I/R compared to the vehicle group (P < 0.001). However, SILI was observed to reduce their expression during I/R (P < 0.05). The beneficial effects of SILI can be attributed to the modulation of Lipin-1 and Lipin-2 gene expression during I/R, which is likely one of the mechanisms underlying its beneficial effects during I/R.
本研究旨在探讨水飞蓟宾（SILI）对肝脏热缺血再灌注（I/R）过程中Lipin-1和Lipin-2基因表达的影响。采用网络药理学方法确定SILI在肝脏炎症背景下的潜在靶点，并阐明其调节Lipin基因表达的潜在机制。将大鼠分为四组，每组八只：（1）载体组：这些大鼠接受正中剖腹术，并给予生理盐水。（2）SILI组：该组大鼠在剖腹术后接受50mg/kg的SILI。（3）I/R组：该组大鼠经历I/R，并给予生理盐水。（4）I/R+SILI组：在该组中，大鼠在I/R过程中接受SILI治疗。采用蛋白质免疫印迹法和实时定量PCR法检测蛋白质水平，并评估Lipin-1和Lipin-2基因的表达。分析确定了SILI（严重急性肝损伤）和肝脏炎症之间的18个共同靶点，这些靶点与107条KEGG通路相关，其中mTOR信号通路是与Lipin的关键连接。对mTOR信号通路中的靶点进行对接研究，结果显示PIK3CA的结合能为-9.7kcal/mol，mTOR蛋白的结合能为-10.4kcal/mol。此外，与载体组相比，I/R期间Lipin-1和Lipin-2基因的蛋白质水平和基因表达显著升高（P<0.001）。然而，观察到SILI在I/R期间可降低它们的表达（P<0.05）。SILI的有益作用可能归因于其在I/R期间对Lipin-1和Lipin-2基因表达的调节，这可能是其在I/R期间产生有益作用的潜在机制之一。
