内质网应激在蛛网膜下腔出血后早期脑损伤中的作用机制

目的探讨内质网应激（ERS）在蛛网膜下腔出血（SAH）后早期脑损伤中的作用机制。方法采用血管穿刺法制作大鼠SAH模型，应用ERS 激动剂衣霉素（Tm）、抑制剂牛磺熊去氧胆酸（TUDCA）以及自噬抑制剂3- 甲基腺嘌呤（3-MA）研究ERS 与自噬在SAH 后早期脑损伤中的作用。在SAH 模型建立后24h对大鼠进行神经功能评估，留取脑组织后分别行分子生物学和免疫组织化学检测。结果SAH后24h ERS水平显著激活，Tm预处理可显著改善SAH 大鼠的神经功能，抑制促凋亡分子caspase-3的表达，减少TUNEL阳性细胞的数量。TUDCA则显著加重SAH 大鼠神经功能障碍并导致神经细胞凋亡。Western blot结果显示，Tm预处理可显著降低自噬标记蛋白Beclin 1表达水平及LC3-Ⅱ/LC3-Ⅰ比值，而TUDCA 具有相反的作用。通过侧脑室内给予3-MA则可显著抑制Tm介导的抗凋亡作用。结论ERS对SAH后早期脑损伤具有神经保护作用，该作用与自噬的激活密切相关。

Autophagy is involved in endoplasmic reticulum stress-related neuroprotection against apoptosis in rat subarachnoid hemorrhage

Objective To investigate whether autophagy activation participates in the neuroprotective effects of endoplasmic reticulum (ER) stress-related neuroprotection in rat subarachnoid hemorrhage. Methods The rats were treated with ER stress inducer tunicamycin (Tm) or inhibitor tauroursodeoxycholic acid (TUDCA) intraperitoneally, then subarachnoid hemorrhage(SAH) was induced by endovascular perforation was performed in a total of 84 rats to induce. Autophagy inhibitor 3-methyladenine (3-MA) was administrated by intracerebral ventricular infusion to determine the relationship between autophagy and ER stress. Neurological evaluation was performed at 24 h after SAH, then all animals were sacrificed and their brain samples were collected for molecular biology and histology studies. Results ER stress level was increased in rats after 24 h of SAH. Pretreatment with Tm significantly improved neurological deficits, reduced the expression of caspase-3 and the number of TUNEL-positive cells. Pretreatment with TUDCA significantly aggravated neurological deficits and cell apoptosis. Western blot analysis revealed that levels of the autophagic protein Beclin 1 and the ratio of LC3-II to LC3-I were increased in Tm group and reduced in TUDCA group. Pretreatment with 3-MA blocked the Tm-induced anti-apoptotic effects. Conclusion Autophagy activation might contribute to ER stress-related neuroprotection in early brain injury following SAH in rats.