门静脉高压(PHT)是肝硬化的主要病因。门体侧支血管的形成和内脏血管舒张有助于高动力循环的发展,这反过来又加重了PHT并增加了并发症的风险。为了研究PHT中肠系膜小动脉的变化,结扎胆总管建立肝硬化大鼠模型。4周后,肝硬化大鼠患有严重的PHT和内脏高动力循环,以门静脉压力(PP)增加为特征,心输出量(CO),心脏指数(CI),肠系膜上动脉(SMA)血流。肝硬化大鼠的肠系膜小动脉表现出明显的血管舒张,血管重塑,和收缩不足。基于这些发现进行RNA测序。共检测到1637个差异表达基因(DEGs),889个上调基因和748个下调基因。与血管变化相关的信号通路被丰富,包括血管内皮生长因子(VEGF),磷脂酰肌醇-3-激酶-AKT(PI3K-AKT),活化B细胞的核因子κ轻链增强子(NF-κB)信号通路,在其他人中。此外,根据蛋白质-蛋白质相互作用(PPI)网络中的程度节点筛选前十大hub基因。功能富集分析表明,hub基因参与细胞周期调控,有丝分裂,和细胞对氧化应激和一氧化氮(NO)的反应。此外,用于改善PHT的有希望的候选药物,如白藜芦醇,是基于集线器基因预测的。一起来看,我们的研究强调了肝硬化PHT大鼠肠系膜小动脉的显着变化。转录组分析揭示了内脏高动力循环中血管变化的潜在分子机制。
Portal hypertension (PHT) is a major cause of liver cirrhosis. The formation of portosystemic collateral vessels and splanchnic vasodilation contribute to the development of hyperdynamic circulation, which in turn aggravates PHT and increases the risk of complications. To investigate the changes in mesenteric arterioles in PHT, cirrhotic rat models were established by ligating the common bile ducts. After 4 weeks, the cirrhotic rats suffered from severe PHT and splanchnic hyperdynamic circulation, characterized by increased portal pressure (PP), cardiac output (CO), cardiac index (CI), and superior mesenteric artery (SMA) flow. Mesenteric arterioles in cirrhotic rats displayed remarkable vasodilation, vascular remodeling, and hypocontractility. RNA sequencing was performed based on these findings. A total of 1,637 differentially expressed genes (DEGs) were detected, with 889 up-regulated and 748 down-regulated genes. Signaling pathways related to vascular changes were enriched, including the vascular endothelial growth factor (VEGF), phosphatidylinositol-3-kinase-AKT (PI3K-AKT), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) signaling pathway, among others. Moreover, the top ten hub genes were screened according to the degree nodes in the protein-protein interaction (PPI) network. Functional enrichment analyses indicated that the hub genes were involved in cell cycle regulation, mitosis, and cellular response to oxidative stress and nitric oxide (NO). In addition, promising candidate drugs for ameliorating PHT, such as resveratrol, were predicted based on hub genes. Taken together, our study highlighted remarkable changes in the mesenteric arterioles of cirrhotic rats with PHT. Transcriptome analyses revealed the potential molecular mechanisms of vascular changes in splanchnic hyperdynamic circulation.