Emergency Department of China-Japan Friendship Hospital, Beijing, China.
Surgical Intensive Care Unit of China-Japan Friendship Hospital, Beijing, China.
Aging (Albany NY). 2020 Mar 28;12(6):5411-5422. doi: 10.18632/aging.102964.
This study was aimed at investigating the regulation of mitochondrial function by histone deacetylase 6 (HDAC6) and the role of HDAC6 in the development and progression of sepsis.
HDAC6 downregulated PHB1 and subsequently promoted the development of CLP-induced sepsis. Inhibition of HDAC6 significantly attenuated CLP-induced sepsis through inhibition of mitochondrial dysfunction and reduced oxidant production, thus protecting the rats from oxidative injury.
In this sepsis model, HDAC6 inhibits the expression and function of PHB1 and alters the function of the mitochondrial respiratory chain mediated by PHB1, thus enhancing the production of oxidants and increasing oxidative stress and thereby leading to severe oxidative injury in multiple organs.
The expression of HDAC6 and prohibitin 1 (PHB1) in humans and in a rat model of sepsis was measured by quantitative reverse-transcription PCR and western blotting. Sepsis induction by cecal ligation and puncture (CLP) was confirmed by histological analysis. Concentrations of different sepsis markers were measured by an enzyme-linked immunosorbent assay, and mitochondrial function was assessed via the mitochondrial respiratory control rate.
本研究旨在探讨组蛋白去乙酰化酶 6（HDAC6）对线粒体功能的调节作用及其在脓毒症发生发展中的作用。
HDAC6 下调 PHB1，进而促进 CLP 诱导的脓毒症的发生。抑制 HDAC6 通过抑制线粒体功能障碍和减少氧化产物的产生，显著减轻 CLP 诱导的脓毒症，从而保护大鼠免受氧化损伤。
在该脓毒症模型中，HDAC6 抑制 PHB1 的表达和功能，并改变 PHB1 介导的线粒体呼吸链功能，从而增加氧化剂的产生，增加氧化应激，导致多个器官发生严重氧化损伤。
通过定量逆转录 PCR 和 Western blot 检测 HDAC6 和抑素 1（PHB1）在人和脓毒症大鼠模型中的表达。通过结扎和穿刺盲肠（CLP）诱导脓毒症，并通过组织学分析进行确认。通过酶联免疫吸附试验测量不同脓毒症标志物的浓度，并通过线粒体呼吸控制率评估线粒体功能。
