Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
J Cell Mol Med. 2022 May;26(9):2594-2606. doi: 10.1111/jcmm.17261. Epub 2022 Apr 2.
This study was performed to uncover the effects of dexmedetomidine on oxidative stress injury induced by mitochondrial localization of telomerase reverse transcriptase (TERT) in enteric glial cells (EGCs) following intestinal ischaemia-reperfusion injury (IRI) in rat models. Following establishment of intestinal IRI models by superior mesenteric artery occlusion in Wistar rats, the expression and distribution patterns of TERT were detected. The IRI rats were subsequently treated with low or high doses of dexmedetomidine, followed by detection of ROS, MDA and GSH levels. Calcein cobalt and rhodamine 123 staining were also carried out to detect mitochondrial permeability transition pore (MPTP) and the mitochondrial membrane potential (MMP), respectively. Moreover, oxidative injury of mtDNA was determined, in addition to analyses of EGC viability and apoptosis. Intestinal tissues and mitochondria of EGCs were badly damaged in the intestinal IRI group. In addition, there was a reduction in mitochondrial localization of TERT, oxidative stress, whilst apoptosis of EGCs was increased and proliferation was decreased. On the other hand, administration of dexmedetomidine was associated with promotion of mitochondrial localization of TERT, whilst oxidative stress, MPTP and mtDNA in EGCs, and EGC apoptosis were all inhibited, and the MMP and EGC viability were both increased. A positive correlation was observed between different doses of dexmedetomidine and protective effects. Collectively, our findings highlighted the antioxidative effects of dexmedetomidine on EGCs following intestinal IRI, as dexmedetomidine alleviated mitochondrial damage by enhancing the mitochondrial localization of TERT.
本研究旨在揭示内质网定位端粒酶逆转录酶(TERT)在大鼠肠缺血再灌注损伤(IRI)模型中对肠嗜铬细胞(EGC)氧化应激损伤的影响。通过结扎肠系膜上动脉建立 Wistar 大鼠肠 IRI 模型,检测 TERT 的表达和分布模式。然后用低剂量或高剂量右美托咪定处理 IRI 大鼠,检测 ROS、MDA 和 GSH 水平。用钙钴和罗丹明 123 染色分别检测线粒体通透性转换孔(MPTP)和线粒体膜电位(MMP)。此外,还测定了 mtDNA 的氧化损伤,以及 EGC 活力和凋亡的分析。肠 IRI 组的肠组织和 EGC 线粒体严重受损。此外,TERT 的线粒体定位减少,氧化应激增加,而 EGC 凋亡增加,增殖减少。另一方面,右美托咪定的给药与 TERT 的线粒体定位促进有关,同时抑制了 EGC 中的氧化应激、MPTP 和 mtDNA,以及 EGC 凋亡,而 MMP 和 EGC 活力都增加。右美托咪定的不同剂量与保护作用呈正相关。总之,我们的研究结果强调了右美托咪定对肠 IRI 后 EGC 的抗氧化作用,因为右美托咪定通过增强 TERT 的线粒体定位来减轻线粒体损伤。