Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China.
Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, 229# North Taibai Road, Xi'an 710069, China.
Int J Mol Sci. 2022 Sep 6;23(18):10248. doi: 10.3390/ijms231810248.
Hibernators are a natural model of vascular ischemia-reperfusion injury; however, the protective mechanisms involved in dealing with such an injury over the torpor-arousal cycle are unclear. The present study aimed to clarify the changes in the thoracic aorta and serum in summer-active (SA), late-torpor (LT) and interbout-arousal (IBA) Daurian ground squirrels (). The results show that total antioxidant capacity (TAC) was unchanged, but malondialdehyde (MDA), hydrogen peroxide (HO), interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were significantly increased for the LT group, whereas the levels of superoxide dismutase (SOD) and interleukin-10 (IL-10) were significantly reduced in the LT group as compared with the SA group. Moreover, the levels of MDA and IL-1β were significantly reduced, whereas SOD and IL-10 were significantly increased in the IBA group as compared with the SA group. In addition, the lumen area of the thoracic aorta and the expression of the smooth muscle cells (SMCs) contractile marker protein 22α (SM22α) were significantly reduced, whereas the protein expression of the synthetic marker proteins osteopontin (OPN), vimentin (VIM) and proliferating cell nuclear antigen (PCNA) were significantly increased in the LT group as compared with the SA group. Furthermore, the smooth muscle layer of the thoracic aorta was significantly thickened, and PCNA protein expression was significantly reduced in the IBA group as compared with the SA group. The contractile marker proteins SM22α and synthetic marker protein VIM underwent significant localization changes in both LT and IBA groups, with localization of the contractile marker protein α-smooth muscle actin (αSMA) changing only in the IBA group as compared with the SA group. In tunica intima, the serum levels of heparin sulfate (HS) and syndecan-1 (Sy-1) in the LT group were significantly reduced, but the serum level of HS in the IBA group increased significantly as compared with the SA group. Protein expression and localization of endothelial nitric oxide synthase (eNOS) was unchanged in the three groups. In summary, the decrease in reactive oxygen species (ROS) and pro-inflammatory factors and increase in SOD and anti-inflammatory factors during the IBA period induced controlled phenotypic switching of thoracic aortic SMCs and restoration of endothelial permeability to resist ischemic and hypoxic injury during torpor of Daurian ground squirrels.
冬眠动物是血管缺血再灌注损伤的天然模型;然而,在蛰伏-觉醒周期中处理这种损伤的保护机制尚不清楚。本研究旨在阐明夏眠活跃(SA)、晚期蛰伏(LT)和间觉觉醒(IBA)东北地松鼠()的胸主动脉和血清中的变化。结果表明,总抗氧化能力(TAC)不变,但丙二醛(MDA)、过氧化氢(HO)、白细胞介素-1β(IL-1β)和肿瘤坏死因子α(TNFα)在 LT 组显著升高,而超氧化物歧化酶(SOD)和白细胞介素-10(IL-10)的水平在 LT 组显著降低与 SA 组相比。此外,与 SA 组相比,IBA 组 MDA 和 IL-1β 的水平显著降低,而 SOD 和 IL-10 的水平显著升高。此外,胸主动脉管腔面积和收缩标志物平滑肌细胞 22α(SM22α)的蛋白表达显著降低,而骨桥蛋白(OPN)、波形蛋白(VIM)和增殖细胞核抗原(PCNA)的合成标志物蛋白表达显著升高在 LT 组与 SA 组相比。此外,胸主动脉平滑肌层明显增厚,IBA 组 PCNA 蛋白表达明显低于 SA 组。收缩标志物蛋白 SM22α和合成标志物蛋白 VIM 在 LT 和 IBA 组均发生明显的定位变化,仅在 IBA 组中,收缩标志物蛋白α-平滑肌肌动蛋白(αSMA)的定位发生变化与 SA 组相比。在内膜中,LT 组肝素硫酸(HS)和 syndecan-1(Sy-1)的血清水平显著降低,但 IBA 组的 HS 血清水平与 SA 组相比显著升高。三组内皮型一氧化氮合酶(eNOS)的蛋白表达和定位不变。总之,IBA 期间活性氧(ROS)和促炎因子的减少以及 SOD 和抗炎因子的增加,诱导东北地松鼠蛰伏期间胸主动脉平滑肌细胞的可控表型转换,并恢复内皮对缺血和缺氧损伤的通透性。