Cerebral ischemia-reperfusion (I/R) injury is an inflammation-related disease. CHRFAM7A can regulate inflammatory responses. Therefore, the present study investigated the mechanism of CHRFAM7A in cerebral I/R injury. CHRFAM7A expression and inflammatory cytokine levels in patients with cerebral I/R injury and oxygen-glucose deprivation/reperfusion (OGD/R)-treated microglia were detected. The proliferation, inflammatory cytokine expressions, nod-like receptor protein 3 (NLRP3) level, cell pyroptosis, and viability and lactate dehydrogenase (LDH) activity in OGD/R-treated microglia were detected after CHRFAM7A overexpression. The NLRP3/Caspase-1 pathway was activated to assess the effect of CHRFAM7A on microglia. Expressions of microglial M1 phenotype marker iNOS and M2 marker Arg1 were detected. Downregulated CHRFAM7A and elevated inflammatory cytokine levels were observed in patients with cerebral I/R injury and OGD/R-treated microglia. In OGD/R-treated microglia, CHRFAM7A overexpression promoted cell proliferation and viability, reduced inflammation and LDH activity, and inhibited NLRP3 inflammasome activation and cell pyroptosis. Mechanically, CHRFAM7A inhibited microglia pyroptosis via inhibiting the NLRP3/Caspase-1 pathway and reduced cell inflammatory injury via promoting microglia polarization from M1 to M2. Overall, CHRFAM7A overexpression attenuated cerebral I/R injury by inhibiting microglia pyroptosis in a NLRP3/Caspase-1 pathway-dependent manner and promoting microglia polarization to M2 phenotype.

脑缺血再灌注（I/R）损伤是一种炎症相关疾病。 CHRFAM7A 可以调节炎症反应。因此，本研究探讨CHRFAM7A在脑I/R损伤中的作用机制。检测脑缺血再灌注损伤和氧糖剥夺/再灌注（OGD/R）治疗的小胶质细胞中CHRFAM7A的表达和炎性细胞因子水平。检测CHRFAM7A过表达后OGD/R处理的小胶质细胞的增殖、炎症细胞因子表达、结节样受体蛋白3（NLRP3）水平、细胞焦亡以及活力和乳酸脱氢酶（LDH）活性。激活 NLRP3/Caspase-1 通路以评估 CHRFAM7A 对小胶质细胞的影响。检测小胶质细胞M1表型标志物iNOS和M2标志物Arg1的表达。在脑 I/R 损伤和 OGD/R 治疗的小胶质细胞患者中观察到 CHRFAM7A 下调和炎症细胞因子水平升高。在 OGD/R 处理的小胶质细胞中，CHRFAM7A 过表达促进细胞增殖和活力，减少炎症和 LDH 活性，并抑制 NLRP3 炎性体激活和细胞焦亡。从机械角度来看，CHRFAM7A通过抑制 NLRP3/Caspase-1 通路抑制小胶质细胞焦亡，并通过促进小胶质细胞从 M1 极化到 M2 来减少细胞炎症损伤。总体而言，CHRFAM7A 过表达通过以 NLRP3/Caspase-1 通路依赖性方式抑制小胶质细胞焦亡并促进小胶质细胞极化为 M2 表型，从而减轻脑 I/R 损伤。