Carnosine suppresses oxygen-glucose deprivation/recovery-induced proliferation and migration of reactive astrocytes of rats in vitro
Carnosine suppresses oxygen-glucose deprivation/recovery-induced proliferation and migration of reactive astrocytes of rats in vitro
复制标题
肌肽抑制氧糖剥夺/恢复诱导的大鼠体外反应性星形胶质细胞的增殖和迁移
DOI：
10.1038/aps.2017.126
复制
发表时间：
2018-01-01
影响因子：
8.2
通讯作者：
Lyu, Jian-xin
中科院分区：
文献类型：
--
作者：
Li Ou-Yang;Liu, Yuan;Lyu, Jian-xin
过度星形胶质细胞增生性瘢痕的形成限制了轴突的再生，损害了功能的恢复，因此对过度星形胶质细胞增生症的干预对脑缺血后神经功能的恢复至关重要。本研究观察了内源性水溶性二肽(β-丙氨酰-L-组氨酸)对体外培养的缺氧缺糖/复氧(OGD/R)细胞星形胶质细胞增殖的影响。原代培养的大鼠星形胶质细胞在缺氧/再灌流2 h后，细胞增殖显著增加，肌肽(5 mm o/L)可引起反应性星形胶质细胞G1期停滞，显著抑制缺氧/再灌流诱导的细胞周期蛋白D1表达的增加，并抑制缺氧/再灌流诱导的反应性星形胶质细胞的增殖。肌肽治疗也逆转了糖酵解和ATP的产生，在OGD后24小时恢复时升高。OGD后24 h反应性星形胶质细胞迁移明显增加，而肌肽治疗逆转了MMP9的表达水平，抑制了星形胶质细胞的迁移。此外，在缺血条件下，肌肽还能促进与星形胶质细胞共培养的皮质神经元的轴突生长。这些结果表明，肌肽可能是抑制脑缺血后星形胶质细胞增生和促进神经功能恢复的一种有前途的候选药物。
Glial scar formation resulted from excessive astrogliosis limits axonal regeneration and impairs recovery of function, thus an intervention to ameliorate excessive astrogliosis is crucial for the recovery of neurological function after cerebral ischemia. In this study we investigated the effects of carnosine, an endogenous water-soluble dipeptide (beta-alanyl-L-histidine), on astrogliosis of cells exposed to oxygen-glucose deprivation/recovery (OGD/R) in vitro. Primary cultured rat astrocytes exhibited a significant increase in proliferation at 24 h recovery after OGD for 2 h. Pretreatment with carnosine (5 mmol/L) caused G1 arrest of reactive astrocytes, significantly attenuated OGD/R-induced increase in cyclin D1 protein expression and suppressed OGD/R-induced proliferation of reactive astrocytes. Carnosine treatment also reversed glycolysis and ATP production, which was elevated at 24 h recovery after OGD. A marked increase in migration of reactive astrocytes was observed at 24 h after OGD, whereas carnosine treatment reversed the expression levels of MMP-9 and suppressed the migration of astrocytes. Furthermore, carnosine also improved neurite growth of cortical neurons co-cultured with astrocytes under ischemic conditions. These results demonstrate that carnosine may be a promising candidate for inhibiting astrogliosis and promoting neurological function recovery after ischemic stroke.