Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Microsc Res Tech. 2024 Mar;87(3):424-433. doi: 10.1002/jemt.24431. Epub 2023 Oct 28.
Remote ischemic postconditioning (RIPostC) alleviates brain ischemic injury through several pathways, including endoplasmic reticulum (ER) stress modulation. Sarco endoplasmic reticulum Ca -ATPase(SERCA2) which plays vital role in calcium homeostasis regulation could modulate ER stress logically. This study aimed to investigate whether RIPostC exerts its neuroprotective effect by reducing ER stress mediated by SERCA2. Male SD rats underwent transient middle cerebral artery occlusion (tMCAO) for 2 h followed by reperfusion, with the RIPostC group undergoing 3 cycles of bilateral femoral artery clamping and reperfusion at the beginning of reperfusion. Stroke outcome was assessed based on infarct volume and neurological function evaluation. Protein levels of SERCA2 and other ER stress markers were measured using Western blotting, immunofluorescence, and immunohistochemistry techniques. Compared to the sham group, we observed that RIPostC can effectively reduce cerebral infarct volume after I/R (34.55%: 21.03%; p = .004) and improve neurological function deficit (9.67:12.5; p = .029). Additionally, RIPostC increased SERCA2 protein expression and decreased the protein level of glucose-regulated protein 78 (GRP78), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) and CCAAT/EBP homologous protein (CHOP). Furthermore, B-cell lymphoma-2 (Bcl-2) expression was increased, while Bcl-2-associated X protein (Bax) and cleaved-caspase-3 was decreased in response to application of RIPostC. Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation. The significance of this study is to provide a theoretical basis for further exploring the protective mechanism of ischemic stroke by RIPostC. RESEARCH HIGHLIGHTS: Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation, thus achieving a neuroprotective effect.
远程缺血后处理（RIPostC）通过多种途径减轻脑缺血损伤，包括内质网（ER）应激调节。肌浆内质网 Ca -ATP 酶（SERCA2）在钙稳态调节中发挥重要作用，可合理调节 ER 应激。本研究旨在探讨 RIPostC 是否通过降低 SERCA2 介导的 ER 应激发挥其神经保护作用。雄性 SD 大鼠行短暂性大脑中动脉闭塞（tMCAO）2 h 后再灌注，再灌注时 RIPostC 组开始再灌注时行双侧股动脉夹闭和再灌注 3 个循环。根据梗死体积和神经功能评估评估卒中结果。使用 Western blot、免疫荧光和免疫组织化学技术测量 SERCA2 和其他 ER 应激标志物的蛋白水平。与假手术组相比，我们观察到 RIPostC 可有效减少 I/R 后的脑梗死体积（34.55%：21.03%；p=0.004）和改善神经功能缺损（9.67：12.5；p=0.029）。此外，RIPostC 增加 SERCA2 蛋白表达，降低葡萄糖调节蛋白 78（GRP78）、真核翻译起始因子 2α 磷酸化（p-eIF2α）和 CCAAT/增强子结合蛋白同源蛋白（CHOP）的蛋白水平。此外，B 细胞淋巴瘤-2（Bcl-2）表达增加，而 Bcl-2 相关 X 蛋白（Bax）和 cleaved-caspase-3 减少。我们的研究结果表明，RIPostC 改善 tMCAO 大鼠的预后，可能是通过抑制 SERCA2 介导的 ER 应激，促进细胞凋亡下调。本研究的意义在于为进一步探讨 RIPostC 通过缺血性卒中的保护机制提供理论依据。
