PDF(Pubmed)
Abstract：
Sepsis, often resulting from an immune response overreaction to microorganisms and their products, can lead to acute lung injury through inflammation mediated by excessive cytokines. This study aimed to investigate the effects of regorafenib on lung injury in mice following the induction of sepsis. We divided mice into four groups (n=6 each): a sham group (undergoing laparotomy without cecal ligation and puncture [CLP]), a CLP group, a vehicle group, and a regorafenib-treated group (30 mg/kg IP, administered one hour before CLP). TNF-α, IL-1β, VEGF, MPO, caspase-11, and Ang-2 levels were significantly increased (p<0.05) in the CLP group compared to the sham group, while the regorafenib group showed significant reductions in these markers versus the CLP group (p< 0.05). In contrast, Ang-1 levels, which were reduced in the CLP group (p<0.05) compared to the sham group, were elevated in the regorafenib group compared to the CLP group. Quantitative real-time PCR revealed a significant decrease in TIE2 and VE-cadherin mRNA expression in the lung tissue of the CLP group compared to the sham group. There were no significant differences in mRNA expression of the TIE2 gene between the regorafenib and CLP group. However, VE-cadherin significantly increased after regorafenib treatment. Regorafenib demonstrated lung-protective effects through its anti-inflammatory and antiangiogenic activities and its influence on lung tissue mRNA expression of the cadherin gene.
摘要：
脓毒症,通常是由对微生物及其产物的免疫反应过度引起的，可以通过过度细胞因子介导的炎症导致急性肺损伤。本研究旨在探讨瑞戈非尼对脓毒症诱导小鼠肺损伤的影响。我们将小鼠分为四组（每组n=6）：假手术组（进行剖腹手术，不进行盲肠结扎和穿刺[CLP]），CLP集团，一组车辆，和regorafenib治疗组（30mg/kgIP，CLP前一小时给药)。TNF-α,IL-1β,VEGF,MPO,caspase-11和Ang-2水平在CLP组显著高于假手术组(p<0.05),而与CLP组相比，regorafenib组的这些标志物显着降低（p<0.05）。相比之下,Ang-1级,与假手术组相比，CLP组降低(p<0.05)，与CLP组相比，regorafenib组升高。定量实时PCR显示，与假手术组相比，CLP组肺组织中TIE2和VE-cadherinmRNA表达显着降低。瑞戈非尼组与CLP组TIE2基因mRNA表达无显著差异。然而,VE-cadherin在regorafenib治疗后显著增加。Regorafenib通过其抗炎和抗血管生成活性及其对cadherin基因肺组织mRNA表达的影响而证明了肺保护作用。
