Department of Neurosurgery, Shanghai Tenth People's Hospital, Clinical Medical College of Nanjing Medical University, No. 301 Yanchangzhong Road, Shanghai, 200072, China.
Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Inflammation. 2021 Jun;44(3):1023-1034. doi: 10.1007/s10753-020-01398-4. Epub 2021 Jan 6.
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）损伤是一种与炎症相关的疾病。CHRFAM7A 可以调节炎症反应。因此，本研究探讨了 CHRFAM7A 在脑 I/R 损伤中的作用机制。检测了脑 I/R 损伤患者和氧葡萄糖剥夺/再灌注（OGD/R）处理的小胶质细胞中 CHRFAM7A 的表达和炎症细胞因子水平。检测了 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、核苷酸结合寡聚结构域样受体蛋白 3（NLRP3）水平、细胞焦亡、活力和乳酸脱氢酶（LDH）活性。激活 NLRP3/Caspase-1 通路评估 CHRFAM7A 对小胶质细胞的影响。检测小胶质细胞 M1 表型标志物诱导型一氧化氮合酶（iNOS）和 M2 标志物精氨酸酶 1（Arg1）的表达。脑 I/R 损伤患者和 OGD/R 处理的小胶质细胞中 CHRFAM7A 下调，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，降低炎症和 LDH 活性，抑制 NLRP3 炎性小体激活和细胞焦亡。机制上，CHRFAM7A 通过抑制 NLRP3/Caspase-1 通路抑制小胶质细胞焦亡，通过促进小胶质细胞从 M1 向 M2 极化减轻细胞炎症损伤。总之，CHRFAM7A 通过抑制 NLRP3/Caspase-1 通路抑制小胶质细胞焦亡，促进小胶质细胞向 M2 表型极化，从而减轻脑 I/R 损伤。
