Fujian Medical Universtity Union Hospital, Fuzhou, Fujian Province, People's Republic of China.
Institute of Materia Medica, Fujian Academy of Chinese Medical Sciences, Fuzhou, Fujian Province, People's Republic of China.
BMC Complement Med Ther. 2024 Aug 1;24(1):293. doi: 10.1186/s12906-024-04597-w.
Salidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown. This study investigated the effects of salidroside on the endogenous neural regeneration after cerebral I/R and the related mechanism.
Focal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). The rats were intraperitoneally treated salidroside once daily for 7 consecutive days. Neurobehavioral assessments were performed at 3 days and 7 days after the injury. TTC staining was performed to assess cerebral infarct volume. To evaluate the survival of neurons, immunohistochemical staining of Neuronal Nuclei (NeuN) in the ischemic hemisphere were conducted. Also, immunofluorescence double or triple staining of the biomarkers of proliferating neural progenitor cells in Subventricular Zone (SVZ) and striatum of the ischemia hemisphere were performed to investigate the neurogenesis. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of neurotrophic factors (NTFs) brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Expression of Notch1 and its target molecular Hes1 were also analyzed by western-blotting and RT-PCR.
Salidroside treatment ameliorated I/R induced neurobehavioral impairment, and reduced infarct volume. Salidroside also restored NeuN positive cells loss after I/R injury. Cerebral I/R injury significantly increased the expression of 5-Bromo-2'-Deoxyuridine (BrdU) and doublecotin (DCX), elevated the number of BrdU/Nestin/DCX triple-labeled cells in SVZ, and BrdU/Nestin/glial fibrillary acidic protein (GFAP) triple-labeled cells in striatum. Salidroside treatment further promoted the proliferation of BrdU/DCX labeled neuroblasts and BrdU/Nestin/GFAP labeled reactive astrocytes. Furthermore, salidroside elevated the mRNA expression and protein concentration of BDNF and NGF in ischemia periphery area, as well. Mechanistically, salidroside elevated Notch1/Hes1 mRNA expression in SVZ. The protein levels of them were also increased after salidroside administration.
Salidroside enhances the endogenous neural regeneration after cerebral I/R. The mechanism of the effect may involve the regulation of BDNF/NGF and Notch signaling pathway.
红景天苷是红景天中的主要生物活性和药理活性物质。它已被报道具有脑缺血/再灌注（I/R）的神经保护作用。然而，红景天苷是否能增强脑 I/R 后的神经再生仍不清楚。本研究探讨了红景天苷对脑 I/R 后内源性神经再生的影响及其相关机制。
通过短暂性大脑中动脉闭塞/再灌注（MCAO/R）诱导大鼠局灶性脑 I/R。大鼠每天腹腔内给予红景天苷治疗，连续 7 天。伤后 3 天和 7 天进行神经行为评估。TTC 染色评估脑梗死体积。通过免疫组化染色检测缺血半球神经元核（NeuN）评估神经元存活情况。还进行了 SVZ 和缺血半球纹状体中增殖神经祖细胞生物标志物的免疫荧光双重或三重染色，以研究神经发生。此外，采用逆转录-聚合酶链反应（RT-PCR）和酶联免疫吸附试验（ELISA）检测神经营养因子（NTFs）脑源性神经营养因子（BDNF）和神经生长因子（NGF）的表达。通过 Western-blotting 和 RT-PCR 分析 Notch1 及其靶分子 Hes1 的表达。
红景天苷治疗改善了 I/R 引起的神经行为损伤，减少了梗死体积。红景天苷还恢复了 I/R 损伤后 NeuN 阳性细胞的丢失。脑 I/R 损伤显著增加了 BrdU 和双钙蛋白（DCX）的表达，增加了 SVZ 中 BrdU/Nestin/DCX 三重标记细胞的数量，并增加了纹状体中 BrdU/Nestin/胶质纤维酸性蛋白（GFAP）三重标记细胞的数量。红景天苷治疗进一步促进了 BrdU/DCX 标记神经前体细胞和 BrdU/Nestin/GFAP 标记反应性星形胶质细胞的增殖。此外，红景天苷还提高了缺血周边区域 BDNF 和 NGF 的 mRNA 表达和蛋白浓度。在机制上，红景天苷增加了 SVZ 中的 Notch1/Hes1 mRNA 表达。给予红景天苷后，其蛋白水平也升高。
红景天苷增强了脑 I/R 后的内源性神经再生。其作用机制可能涉及 BDNF/NGF 和 Notch 信号通路的调节。
