Cerebral ischemia/reperfusion (I/R) injury is the result of ischemic stroke, a serious threat to public health. I/R injury can damage the blood–brain barrier (BBB), adversely affecting the brain environment and aggravating the injury. Cyclo-(Phe-Tyr) (sparganin C, SC) is a small molecule derived from the Chinese yam Dioscorea opposita Thunb. or Sparganii rhizoma. In our previous study, SC mitigates I/R injury both in vivo and in vitro through the action of JUNB and SOX5. However, the exact pharmacological effects of SC on BBB protection after an I/R injury remain unclear. We constructed a rat model of middle cerebral artery occlusion–reperfusion (MCAO/R) injury to evaluate the therapeutic actions of SC, and the integrity of the BBB was evaluated by ELISA, western blotting, and Evans blue staining. It was found that SC significantly reduced the amount of Evans blue staining in the brain, inhibited the expression of inflammatory factors IL-6, IL-1β, IL-17, IL-23, and TNF-α as well as TIPM1/MMP proteins, and promoted the expression of the tight junction proteins occludin, ZO-1, and claudin-5. SC was found to inhibit the excess autophagy induced by I/R injury to protect BBB integrity through the PI3K/AKT/mTOR pathway, and the PI3K inhibitor LY294002 significantly reduced the SC-mediated protection. Overall, this is the first demonstration of the alleviation of BBB damage caused by I/R injury by SC and suggests a potential treatment for the effects of an ischemic stroke.

中文翻译：

---

Cyclo-(Phe-Tyr) 通过调节自噬减少脑缺血/再灌注引起的血脑屏障功能障碍

脑缺血/再灌注 (I/R) 损伤是缺血性中风的结果，对公众健康构成严重威胁。I/R 损伤会破坏血脑屏障 (BBB)，对大脑环境产生不利影响并加重损伤。Cyclo-(Phe-Tyr) (sparganin C, SC) 是一种源自山药Dioscorea opposita Thunb 的小分子。或三棱根。在我们之前的研究中，SC 减轻了体内和体外的 I/R 损伤通过 JUNB 和 SOX5 的作用。然而，SC 对 I/R 损伤后 BBB 保护的确切药理作用仍不清楚。我们构建了大脑中动脉闭塞再灌注 (MCAO/R) 损伤大鼠模型来评估 SC 的治疗作用，并通过 ELISA、蛋白质印迹和伊文思蓝染色评估 BBB 的完整性。发现SC显着降低脑内伊文思蓝染色量，抑制炎症因子IL-6、IL-1β、IL-17、IL-23和TNF-α以及TIPM1/MMP蛋白的表达, 并促进紧密连接蛋白 occludin、ZO-1 和 claudin-5 的表达。SC 被发现抑制 I/R 损伤诱导的过度自噬，通过 PI3K/AKT/mTOR 通路保护 BBB 完整性，和 PI3K 抑制剂 LY294002 显着降低了 SC 介导的保护作用。总的来说，这是第一次证明 SC 可以减轻 I/R 损伤引起的 BBB 损伤，并表明可能治疗缺血性中风的影响。