Liu Nannuan, Xu Yue, Liu Yao, Chen Tao, Hu Wenli
Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China.
Curr Pharm Des. 2025;31(12):981-991. doi: 10.2174/0113816128322927241015120431.
This study aimed to explore whether Galangin (Gal) could improve cerebral Ischemiareperfusion (I/R) injury by regulating astrocytes, and clarify its potential molecular mechanism.
An I/R injury model of rats was established using the Middle Cerebral Artery Occlusion/Reperfusion (MCAO/R) method, followed by the administration of Gal (25, 50, 100 mg/kg) via gavage for 14 consecutive days. Besides, astrocytes were isolated from the rats to construct an Oxygen-Glucose Deprivation/Re-oxygenation (OGD/R) cell model, with treatments of Gal or the Ras homolog gene family member A (RhoA)/Rho-associated Coiled-coil containing protein Kinase (ROCK) inhibitor Y-27632. Subsequently, the severity of nerve injury was assessed using the modified Neurological Severity Score (mNSS) test; behavioral disorders in I/R rats were observed through the open field and ladder-climbing tests. Pathological damages and neuron survival in the peri-infarct zone were examined by hematoxylin and eosin staining and NeuN staining, respectively. Additionally, immunofluorescence staining was employed to determine astrocyte polarization and TUNEL staining was carried out to measure the level of cell apoptosis; also, western blot was performed to detect the expression of proteins related to the RhoA/ROCK/LIM domain Kinase (LIMK) pathway.
Gal significantly ameliorated the neurological and motor dysfunctions caused by I/R in rats, reduced pathological damage in the peri-infarct zone, and promoted neuronal survival. Additionally, Gal increased the number of A2 astrocytes, while it decreased the number of A1 astrocytes. In vitro experiments revealed that the effect of Gal was consistent with that of Y-27632. Additionally, Gal significantly enhanced the survival of OGD/R cells, increased the number of A2 astrocytes, and inhibited the expression of proteins associated with the RhoA/ROCK pathway.
Gal could reduce the level of apoptosis, promote the polarization of A2 astrocytes, and improve cerebral I/R injury, and its mechanism may be related to the inhibition of the RhoA/ROCK pathway.
本研究旨在探讨高良姜素（Gal）是否可通过调节星形胶质细胞来改善脑缺血再灌注（I/R）损伤，并阐明其潜在的分子机制。
采用大脑中动脉闭塞/再灌注（MCAO/R）法建立大鼠I/R损伤模型，随后连续14天经口灌胃给予Gal（25、50、100mg/kg）。此外，从大鼠中分离星形胶质细胞以构建氧-葡萄糖剥夺/复氧（OGD/R）细胞模型，用Gal或Ras同源基因家族成员A（RhoA）/Rho相关卷曲螺旋蛋白激酶（ROCK）抑制剂Y-27632进行处理。随后，使用改良神经功能缺损评分（mNSS）测试评估神经损伤的严重程度；通过旷场试验和爬梯试验观察I/R大鼠的行为障碍。分别采用苏木精-伊红染色和NeuN染色检查梗死灶周围区域的病理损伤和神经元存活情况。此外，采用免疫荧光染色确定星形胶质细胞极化，并进行TUNEL染色以测量细胞凋亡水平；同时，进行蛋白质免疫印迹法检测与RhoA/ROCK/亮氨酸拉链激酶（LIMK）途径相关的蛋白质表达。
Gal显著改善了I/R所致大鼠的神经功能和运动功能障碍，减少了梗死灶周围区域的病理损伤，并促进了神经元存活。此外，Gal增加了A2星形胶质细胞的数量，同时减少了A1星形胶质细胞的数量。体外实验表明，Gal的作用与Y-27632一致。此外，Gal显著提高了OGD/R细胞的存活率，增加了A2星形胶质细胞的数量，并抑制了与RhoA/ROCK途径相关的蛋白质表达。
Gal可降低细胞凋亡水平，促进A2星形胶质细胞极化，改善脑I/R损伤，其机制可能与抑制RhoA/ROCK途径有关。
