Department of Fundamental Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea.
Int J Mol Sci. 2024 Jul 10;25(14):7567. doi: 10.3390/ijms25147567.
Inhibitors of sodium/glucose cotransporter 2 (SGLT2), such as empagliflozin and canagliflozin, have been widely used to block glucose reabsorption in the proximal tubules of kidneys in patients with diabetes. A meta-analysis suggested that SGLT2 inhibitors are associated with a decreased risk of asthma development. Therefore, we investigated whether SGLT2 inhibitors could suppress allergic asthma. Empagliflozin and canagliflozin suppressed the in vitro degranulation reaction induced by antigens in a concentration-dependent manner in RBL-2H3 mast cells. Empagliflozin and canagliflozin were administered to BALB/c mice sensitized to ovalbumin (OVA). The administration of empagliflozin or canagliflozin significantly suppressed OVA-induced airway hyper-responsiveness and increased the number of immune cells and pro-inflammatory cytokine mRNA expression levels in bronchoalveolar lavage fluid. The administration of empagliflozin and canagliflozin also suppressed OVA-induced histopathological changes in the lungs. Empagliflozin and canagliflozin also suppressed serum IgE levels. These results suggested that empagliflozin and canagliflozin may be applicable for the treatment of allergic asthma by suppressing immune responses.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂，如恩格列净和卡格列净，已被广泛用于阻止糖尿病患者肾脏近端小管对葡萄糖的重吸收。一项荟萃分析表明，SGLT2 抑制剂与哮喘发病风险降低相关。因此，我们研究了 SGLT2 抑制剂是否可以抑制过敏性哮喘。恩格列净和卡格列净可抑制 RBL-2H3 肥大细胞中抗原诱导的体外脱颗粒反应，呈浓度依赖性。恩格列净和卡格列净被给予卵清蛋白（OVA）致敏的 BALB/c 小鼠。给予恩格列净或卡格列净可显著抑制 OVA 诱导的气道高反应性，并增加支气管肺泡灌洗液中免疫细胞和促炎细胞因子 mRNA 表达水平。恩格列净和卡格列净还抑制了 OVA 诱导的肺部组织病理学变化。恩格列净和卡格列净还抑制了血清 IgE 水平。这些结果表明，恩格列净和卡格列净可能通过抑制免疫反应适用于治疗过敏性哮喘。
