Angiotensin II receptor blockers (ARBs) have been shown to exert neuroprotective effects by suppressing inflammatory and apoptotic responses. In the present study, the effects of the ARB telmisartan on the NLRP3 inflammasome induced by oxygen-glucose deprivation (OGD) in neural stem cells (NSCs) were investigated, as well as their possible association with the activation of the PI3K pathway. Cultured NSCs were treated with different concentrations of telmisartan and subjected to various durations of OGD. Cell counting, lactate dehydrogenase, bromodeoxyuridine, and colony-forming unit assays were performed to measure cell viability and proliferation. In addition, the activity of intracellular signaling pathways associated with the PI3K pathway and NLRP3 inflammasome was evaluated. Telmisartan alone did not affect NSCs up to a concentration of 10 μM under normal conditions but showed toxicity at a concentration of 100 μM. Moreover, OGD reduced the viability of NSCs in a time-dependent manner. Nevertheless, treatment with telmisartan increased the viability and proliferation of OGD-injured NSCs. Furthermore, telmisartan promoted the expression of survival-related proteins and mRNA while inhibiting the expression of death-related proteins induced by OGD. In particular, telmisartan attenuated OGD-dependent expression of the NLRP3 inflammasome and its related signaling proteins. These beneficial effects of telmisartan were blocked by a PI3K inhibitor. Together, these results indicate that telmisartan attenuated the activation of the NLRP3 inflammasome by triggering the PI3K pathway, thereby contributing to neuroprotection.

血管紧张素 II 受体阻滞剂 (ARB) 已显示通过抑制炎症和细胞凋亡反应发挥神经保护作用。在本研究中，研究了 ARB 替米沙坦对神经干细胞 (NSC) 中氧-葡萄糖剥夺 (OGD) 诱导的 NLRP3 炎症小体的影响，以及它们与 PI3K 通路激活的可能关联。培养的神经干细胞用不同浓度的替米沙坦处理，并接受不同持续时间的 OGD。进行细胞计数、乳酸脱氢酶、溴脱氧尿苷和集落形成单位测定以测量细胞活力和增殖。此外，还评估了与 PI3K 通路和 NLRP3 炎症小体相关的细胞内信号通路的活性。在正常条件下，单独使用替米沙坦在 10 μM 浓度下对 NSC 没有影响，但在 100 μM 浓度下显示出毒性。此外，OGD 以时间依赖性方式降低了 NSC 的活力。然而，替米沙坦治疗增加了 OGD 损伤的神经干细胞的活力和增殖。此外，替米沙坦促进生存相关蛋白和 mRNA 的表达，同时抑制 OGD 诱导的死亡相关蛋白的表达。特别是，替米沙坦减弱了 NLRP3 炎性体及其相关信号蛋白的 OGD 依赖性表达。替米沙坦的这些有益作用被 PI3K 抑制剂阻断。总之，这些结果表明替米沙坦通过触发 PI3K 通路减弱了 NLRP3 炎症小体的激活，从而有助于神经保护。