人参皂苷Rd促进创伤性脑损伤后的内源性神经发生和相关机制研究

Ginsenoside Rd promotes endogenous neurogenesis after traumatic brain injury and related mechanims

目的探讨人参皂苷Rd(GSRd)对创伤性脑损伤(TBI)后内源性神经发生的影响及可能机制。方法取SD雄性大鼠随机分为假手术组、溶剂组和GSRd组。应用液压损伤装置制备大鼠TBI模型,然后尾静脉注射GSRd进行治疗。采用水迷宫实验检测大鼠的学习记忆能力,采用ROS、MDA、SOD试剂盒检测大鼠体内氧化应激水平,采用qPCR法检测损伤区皮质细胞线粒体损伤情况,采用TUENL试剂盒检测损伤区皮质细胞凋亡情况,采用Western blot法检测大鼠海马组织中双肾上腺皮质激素(DCX)蛋白水平,采用NeuN/BrdU免疫荧光法检测损伤区皮质新生神经元情况。结果与溶剂组比较,GSRd组大鼠逃避潜伏期显著缩短,平台穿越次数显著增加,差异有统计学意义(P<0.05);ROS和MDA水平显著降低,SOD活力显著升高,差异有统计学意义(P<0.05);GSRd治疗能抑制损伤区皮质细胞线粒体DNA拷贝数的下降,缓解大鼠损伤区皮质的细胞凋亡,提高损伤侧海马及皮质的神经发生,差异有统计学意义(P<0.05)。结论GSRd能促进TBI大鼠内源性神经发生及学习记忆能力的恢复,这可能与抑制氧化应激及线粒体损伤并减少细胞凋亡有关。

Objective To investigate the effect of ginsenoside Rd(GSRd)on endogenous neurogenesis after traumatic brain injury(TBI)and the possible mechanisms involved.Methods Male SD rats were randomly divided into three groups:a sham group,a solvent group,and a GSRd group.A TBI model was established using a hydraulic injury device,and GSRd was injected via the tail vein.The Morris water maze test was used to assess learning and memory abilities in rats.Oxidative stress levels were detected using ROS,MDA,and SOD detection kits.Mitochondrial damage in the cortical cells of the injured area was detected by qPCR.Apoptosis in the cortical cells of the injured area was examined by TUENL kits.The levels of doublecortin(DCX)in the hippocampal tissue were measured by Western blot.Newly formed neurons in the cortical injury region were examined by NeuN/BrdU immunofluorescence.Results Compared with solvent group,the GSRd group showed a significant decrease in escape latency and a significant increase in the number of platform crossings(P<0.05).ROS and MDA levels were significantly reduced,while SOD activities were significantly enhanced(P<0.05).GSRd treatment inhibited the reduction in mitochondrial DNA copy number in cortical cells,relieved apoptosis in the injured cortical region,and increased neurogenesis in the injured hippocampus and cortex(P<0.05).Conclusions GSRd promotes endogenous neurogenesis and improves the recovery of learning and memory abilities in TBI rats,which may be related to inhibiting oxidative stress,mitochondrial damage,and reducing cell apoptosis.