Institute of Microcirculation, Hebei North University, Hebei Zhangjiakou, PR China.
Hebei Medical University, Shijiazhuang, PR China.
Int J Med Sci. 2020 Jul 30;17(14):2147-2154. doi: 10.7150/ijms.47662. eCollection 2020.
Hemorrhagic shock-induced ischemia and hypoxia elicit endoplasmic reticulum stress (ERS) that leads to cell apoptosis, tissue structural damage and organ dysfunction and failure. Stellate ganglion blockade (SGB) has been demonstrated to improve intestinal barrier dysfunction induced by hemorrhagic shock. The present study sought to investigate whether the beneficial effect of SGB on the intestinal mucosal barrier function is via suppression of ERS. A conscious rat model of hemorrhagic shock (40 ±2 mmHg for 1 hour, followed by resuscitation) was established. The parameters reflecting intestinal morphology and intestinal mucosal barrier function including wet-dry ratio (W/D), intestinal permeability, D-lactic acid (D-LA) and intestinal fatty acid binding protein (I-FABP) in plasma, and expressions of ATF6α, PERK, and IRE1α in intestinal tissues were then observed. Furthermore, the effects of either SGB or ERS inhibitor, 4-phenylbutyric acid (4-PBA), on these parameters in rats with hemorrhagic shock were assessed. The effect of ERS agonist tunicamycin (TM) on the rats subjected with both SGB and hemorrhagic shock was also determined. Either SGB or administration of ERS inhibitor, 4-PBA, alleviated hemorrhagic shock-induced adverse effects such as intestinal mucosal barrier dysfunction and excessive autophagy, which were characterized by damaged intestinal tissue, enhanced intestinal permeability and D-LA and I-FABP levels in plasma, and increased expressions of ATF6α, PERK, IRE1α in intestinal tissue. In contrast, administration of ERS agonist, TM, suppressed the beneficial effects of SGB on intestinal tissue and function during hemorrhagic shock. The SGB repairs intestinal mucosal barrier through suppression of ERS following hemorrhagic shock.
出血性休克引起的缺血缺氧会引发内质网应激（ERS），导致细胞凋亡、组织结构损伤和器官功能障碍和衰竭。星状神经节阻滞（SGB）已被证明可改善出血性休克引起的肠道屏障功能障碍。本研究旨在探讨 SGB 是否通过抑制 ERS 对肠道黏膜屏障功能产生有益影响。建立了出血性休克（40±2mmHg 持续 1 小时，然后复苏）的清醒大鼠模型。观察反映肠道形态和肠道黏膜屏障功能的参数，包括湿干比（W/D）、肠道通透性、血浆中 D-乳酸（D-LA）和肠脂肪酸结合蛋白（I-FABP），以及肠道组织中 ATF6α、PERK 和 IRE1α 的表达。此外，还评估了 SGB 或 ERS 抑制剂 4-苯丁酸（4-PBA）对出血性休克大鼠这些参数的影响。还确定了 ERS 激动剂衣霉素（TM）对同时接受 SGB 和出血性休克的大鼠的影响。SGB 或 ERS 抑制剂 4-PBA 的给药均减轻了出血性休克引起的不良反应，如肠道黏膜屏障功能障碍和过度自噬，其特征为肠道组织损伤、肠道通透性增加以及血浆中 D-LA 和 I-FABP 水平升高，以及肠道组织中 ATF6α、PERK、IRE1α 的表达增加。相反，给予 ERS 激动剂 TM 抑制了 SGB 在出血性休克期间对肠道组织和功能的有益作用。SGB 通过抑制出血性休克后 ERS 来修复肠道黏膜屏障。
