Serum- and glucocorticoid-inducible kinease-1 (SGK1) is a serine/threonine kinase regulated by hypotonic stimuli, which is involved in regulation of cell cycle and apoptosis. Our previous study shows that activation of volume-regulated Cl⁻ channels (VRCCs) protects rat basilar artery smooth muscle cells (BASMCs) against hydrogen peroxide (H₂O₂)-induced apoptosis. In the present study, we investigated whether SGK1 was involved in the protective effect of VRCCs in BASMCs. We showed that hypotonic challenge significantly reduced H₂O₂-induced apoptosis, and increased SGK1 phosphorylation, but did not affect SGK1 protein expression. The protective effect of hypotonic challenge against H₂O₂-induced apoptosis was mediated through inhibiting mitochondria-dependent apoptotic pathway, evidenced by increased Bcl-2/Bax ratio, stabilizing mitochondrial membrane potential (MMP), decreased cytochrome c release from the mitochondria to the cytoplasm, and inhibition of the activation of caspase-9 and caspase-3. These protective effects of hypotonic challenge against H₂O₂-induced apoptosis was diminished and enhanced, respectively, by SGK1 knockdown and overexpression. We further revealed that SGK1 activation significantly increased forkhead box O3a (FOXO3a) phosphorylation, and then inhibited the translocation of FOXO3a into nucleus and the subsequent expression of Bcl-2 interacting mediator of cell death (Bim). In conclusion, SGK1 mediates the protective effect of VRCCs against H₂O₂-induced apoptosis in BASMCs via inhibiting FOXO3a/Bim signaling pathway. Our results provide compelling evidences that SGK1 is a critical link between VRCCs and apoptosis, and shed a new light on the treatment of vascular apoptosis-associated diseases, such as vascular remodeling, angiogenesis, and atherosclerosis.

血清和糖皮质激素诱导的激酶1（SGK1）是由低渗刺激调节的丝氨酸/苏氨酸激酶，参与细胞周期和凋亡的调节。我们以前的研究显示，音量调节的氯的活化^-通道（VRCCs）保护大鼠基底动脉平滑肌细胞（BASMCs）对过氧化氢（H ₂ ö ₂）诱导的细胞凋亡。在本研究中，我们调查了SGK1是否参与了BASMC中VRCC的保护作用。我们显示低渗挑战显着减少H ₂ O ₂诱导的细胞凋亡，并增加SGK1磷酸化，但不影响SGK1蛋白表达。低渗挑战对H ₂的保护作用O ₂诱导的细胞凋亡是通过抑制线粒体依赖性凋亡途径介导的，其表现为Bcl-2 / Bax比增加，线粒体膜电位（MMP）稳定，细胞色素c从线粒体向细胞质的释放减少以及对C2激活的抑制。 caspase-9和caspase-3。低渗挑战对H ₂ O _2的这些保护作用SGK1敲低和过表达分别减少和增强了诱导的凋亡。我们进一步揭示了SGK1激活显着增加了叉头盒O3a（FOXO3a）的磷酸化，然后抑制了FOXO3a进入细胞核的转运，并抑制了Bcl-2相互作用的细胞死亡介质（Bim）的表达。总之，SGK1介导VRCCs针对小时保护效果_2个ö ₂诱导的细胞凋亡经由BASMCs抑制的FOXO3a / Bim的信号传导途径。我们的结果提供了令人信服的证据，表明SGK1是VRCC与细胞凋亡之间的关键纽带，为治疗与血管凋亡相关的疾病（如血管重塑，血管生成和动脉粥样硬化）提供了新的思路。