Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu, Anhui, PR China.
Department of Pathophysiology, School of Medicine, Bengbu Medical College, Bengbu, Anhui, PR China.
Neurosci Lett. 2018 Jan 1;662:219-226. doi: 10.1016/j.neulet.2017.10.037. Epub 2017 Oct 20.
Cerebral ischemia and reperfusion is a common pathophysiologic process, which is involved in stroke and brain trauma. Recent studies revealed that activating epidermal growth factor receptor (EGFR) ameliorates cerebral ischemia/reperfusion (I/R) injury, however, the precise mechanisms remain to be illuminated. In this study, the neurological behavior was evaluated by Longa score. The infarct volume was performed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and the expression of p-EGFR, p-STAT3, connexin (Cx43), Bax and Bcl-2 were detected by Western blot. The neurological behavior and infarct volume were increased in rats with cerebral I/R injury. Epidermal growth factor (EGF) pretreatment significantly decreased neurological deficit and infarct volume. However, the antagonist of EGFR, AG1478 attenuated the EGF-induced reduction of neurological deficit and infarct volume. Moreover, the inhibitor of JAK2/STAT3, AG490 undermined the protective effects stimulated by activating EGFR in rats with I/R injury. In addition, EGF pretreatment increased the expression of Bcl-2 and reduced the expression of Bax and Cx43, and the effects were abolished after using AG1478 and AG490. These findings implicate that JAK2/STAT3 pathway plays the vital role in I/R injury protection from activating EGFR. And the neuroprotective effects may associate with inhibiting the Cx43 expression and the inhibition of apoptosis.
脑缺血再灌注是一种常见的病理生理过程，涉及中风和脑外伤。最近的研究表明，激活表皮生长因子受体（EGFR）可改善脑缺血再灌注（I/R）损伤，但确切的机制仍有待阐明。在这项研究中，通过 Longa 评分评估神经行为。通过 2,3,5-三苯基氯化四氮唑（TTC）染色检测梗死体积，通过 Western blot 检测 p-EGFR、p-STAT3、连接蛋白（Cx43）、Bax 和 Bcl-2 的表达。脑 I/R 损伤大鼠的神经行为和梗死体积增加。表皮生长因子（EGF）预处理可显著降低神经功能缺损和梗死体积。然而，EGFR 的拮抗剂 AG1478 减弱了 EGF 诱导的神经功能缺损和梗死体积减少。此外，JAK2/STAT3 的抑制剂 AG490 削弱了激活 EGFR 对 I/R 损伤大鼠的保护作用。此外，EGF 预处理可增加 Bcl-2 的表达，减少 Bax 和 Cx43 的表达，而使用 AG1478 和 AG490 后则消除了这些作用。这些发现表明 JAK2/STAT3 通路在激活 EGFR 保护 I/R 损伤中起关键作用。神经保护作用可能与抑制 Cx43 表达和抑制细胞凋亡有关。
