Dry Treatment Department of Critical Care Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Xishan, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Xichang, China.
Bioengineered. 2022 May;13(5):12673-12690. doi: 10.1080/21655979.2022.2063560.
Sepsis, a leading contributor to the death of inpatients, results in severe organ dysfunction as complications. The heart is one of the major organs attacked by sepsis, and the effective control of the inflammatory cascade reaction in sepsis is of great significance in alleviating sepsis-associated acute myocardial injury (S-AMI). Chrysophanol, a natural anthraquinone, has been discovered to carry anti-inflammatory effects. The aim of this paper is to probe the impact of Chrysophanol on S-AMI. An S-AMI model was engineered in rats via CLP. Pathological alterations in the myocardial tissues of rats were monitored. qRT-PCR, ELISA, and western blot measured the profiles of miR-27b-3p, Peroxisomal proliferating-activated receptor gamma (PPARG), inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8), and inflammatory response proteins (NF-κB-p65, MAPK-p38, JNK1/2). Besides, miR-27b-3p mimics were transfected into cardiomyocytes, and the proliferation and apoptosis of cardiomyocytes were examined through MTT and flow cytometry. As evidenced by the experimental outcomes, chrysophanol suppressed sepsis-mediated acute myocardial injury and LPS-mediated apoptosis in myocardial cells and lessened the release of pro-inflammatory cytokines and inflammatory response proteins. Moreover, chrysophanol cramped miR-27b-3p expression and heightened PPARG expression. miR-27b-3p targeted PPARG and restrained its expression. On the other hand, the PPARG agonist (RGZ) partially eliminated the apoptosis and pro-inflammatory responses of myocardial cells elicited by LPS. Therefore, this study revealed that Chrysophanol guarded against sepsis-mediated acute myocardial injury through dampening inflammation and apoptosis via the miR-27b-3p-PPARG axis, adding to the references for treating sepsis-AMI.
脓毒症是导致住院患者死亡的主要原因之一,其并发症可导致严重的器官功能障碍。心脏是脓毒症攻击的主要器官之一,有效控制脓毒症中炎症级联反应对缓解脓毒症相关性急性心肌损伤(S-AMI)具有重要意义。大黄素是一种天然蒽醌类化合物,已被发现具有抗炎作用。本文旨在探讨大黄素对 S-AMI 的影响。通过 CLP 在大鼠中构建 S-AMI 模型,监测大鼠心肌组织的病理改变。qRT-PCR、ELISA 和 Western blot 检测 miR-27b-3p、过氧化物酶体增殖物激活受体 γ(PPARG)、炎症细胞因子(TNF-α、IL-1β、IL-6、IL-8)和炎症反应蛋白(NF-κB-p65、MAPK-p38、JNK1/2)的表达谱。此外,将 miR-27b-3p 模拟物转染到心肌细胞中,通过 MTT 和流式细胞术检测心肌细胞的增殖和凋亡。实验结果表明,大黄素抑制脓毒症介导的急性心肌损伤和 LPS 介导的心肌细胞凋亡,减轻促炎细胞因子和炎症反应蛋白的释放。此外,大黄素抑制 miR-27b-3p 的表达并上调 PPARG 的表达。miR-27b-3p 靶向 PPARG 并抑制其表达。另一方面,PPARG 激动剂(RGZ)部分消除了 LPS 引起的心肌细胞凋亡和促炎反应。因此,本研究表明,大黄素通过抑制炎症和凋亡来保护脓毒症介导的急性心肌损伤,为治疗脓毒症相关性急性心肌损伤提供了参考。