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红景天苷促进脑缺血/再灌注后内源性神经再生的作用涉及神经营养因子
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Abstract:
背景：红景天苷是红景天的主要生物活性物质和药理活性物质，有报道称其对脑缺血/再灌注(I/R)具有神经保护作用。然而，红景天苷是否可以增强脑I/R后的神经再生尚不清楚。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相关机制。方法：通过短暂性大脑中动脉闭塞/再灌注(MCAO/R)诱导大鼠局灶性I/R。为了评估神经元的存活率，对缺血半球中的神经核抗原(NeuN)进行免疫组织化学染色。此外，对缺血半球侧脑室下区(SVZ)和纹状体中的增殖性神经祖细胞生物标志物进行免疫荧光双标或三标染色，以研究神经再生情况。此外，使用逆转录聚合酶链式反应(RT-PCR)和酶联免疫吸附测定(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。结果：红景天苷使I/R损伤后NeuN阳性细胞的损失得以恢复。脑I/R损伤显著增加了5-溴脱氧尿苷(BrdU)和doublecotin (DCX)的表达，增加了SVZ中BrdU/Nestin/DCX共同标记细胞的数量，以及纹状体中BrdU/Nestin/胶质纤维酸性蛋白(GFAP)共同标记细胞的数量。红景天苷治疗进一步促进了BrdU/DCX标记的神经母细胞和BrdU/Nestin/GFAP标记的活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。结论：红景天苷可促进脑I/R后的内源性神经再生，其作用机制可能涉及对BDNF/NGF的调节。
Background: 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. Methods: Focal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). 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). Results: 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. Conclusions: Salidroside enhances the endogenous neural
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