The role of hydrogen sulfide (H₂S) on the phenotypic change of astrocytes following cerebral ischemia/reperfusion (I/R) in mice was investigated in present study. We tested the expression of glial fibrillary acidic protein (GFAP), A2 phenotype marker S100a10, and A1 phenotype marker C3 protein and assessed the change of BrdU/GFAP-positive cells, GFAP/C3-positive cells, and GFAP/S100a10-positive cells in mice hippocampal tissues to evaluate the change of astrocyte phenotypes following cerebral I/R. The role of H₂S on the phenotypic change of astrocytes following cerebral I/R in mice was investigated by using H₂S synthase cystathionine-γ-lyase (CSE) knockout mice (KO). The results revealed that cerebral I/R injury promoted the astrocytes proliferation of both A1 and A2 phenotypes, which were more significant in mice of H₂S synthase CSE KO than in mice of wild type (WT). Interestingly, supplement with H₂S could inhibit the A1 phenotype proliferation but promote the proliferation of A2 phenotype, suggesting that H₂S could regulate the transformation of astrocytes to A2 phenotype following cerebral I/R, which is beneficial for neuronal recovery. Besides, we found that H₂S-mediated change of astrocyte phenotype is related to inhibiting the RhoA/ROCK pathway. Furthermore, both H₂S and ROCK inhibitor could ameliorate the brain injury of mice at 9 days after cerebral I/R. In conclusion, H₂S regulates the phenotypic transformation of astrocytes to A2 phenotype following the cerebral I/R via inhibiting RhoA/ROCK pathway and then exerts the neuroprotective effect against the subacute brain injury.

本研究探讨了硫化氢（H ₂ S）对小鼠脑缺血/再灌注（I/R）后星形胶质细胞表型变化的作用。我们检测了胶质纤维酸性蛋白（GFAP）、A2表型标志物S100a10和A1表型标志物C3蛋白的表达，并评估了BrdU/GFAP阳性细胞、GFAP/C3阳性细胞和GFAP/S100a10阳性细胞的变化在小鼠海马组织中评估脑缺血再灌注后星形胶质细胞表型的变化。通过使用H ₂ S合酶胱硫醚-γ-裂解酶(CSE)敲除小鼠(KO)研究H ₂ S对小鼠脑缺血再灌注后星形胶质细胞表型变化的作用。结果显示，脑I/R损伤促进A1和A2表型星形胶质细胞增殖，其中H ₂ S合酶CSE KO小鼠比野生型(WT)小鼠更显着。有趣的是，补充H ₂ S可以抑制A1表型增殖，但促进A2表型增殖，这表明H ₂ S可以调节脑I/R后星形胶质细胞向A2表型的转化，有利于神经元的恢复。此外，我们发现H ₂ S介导的星形胶质细胞表型变化与抑制RhoA/ROCK通路有关。此外，H ₂ S和ROCK抑制剂均能改善小鼠脑缺血再灌注后9天的脑损伤。总之，H ₂ S通过抑制RhoA/ROCK通路调节脑I/R后星形胶质细胞表型向A2表型转变，进而发挥针对亚急性脑损伤的神经保护作用。