人参皂苷Rg1对嗅球摘除抑郁症大鼠模型的抗炎和神经保护作用及其机制研究

Anti-inflammatory and neuroprotective function of ginsenoside Rg1 and its mechanism in olfactory bulbectomized rat model of depression

目的:抑郁症已成为继心血管疾病、糖尿病、肿瘤之后的第四大疾病,严重影响人类生活质量。本文着重探讨人参皂苷Rg1对嗅球摘除抑郁症大鼠模型的抗炎和神经保护作用及其机制。方法:大鼠分为假手术组(对照组)、造模组和治疗组,通过手术摘除建立嗅球摘除抑郁症模型,治疗组术后给予人参皂苷Rg1。高效液相色谱法检测海马组织5-羟色胺(5-HT)浓度。CCK-8实验检测细胞活力。流式细胞术分析细胞凋亡。蛋白印迹法检测5-HT1A受体、增殖标记蛋白细胞增殖核抗原-67(Ki-67)和增殖细胞核抗原(PCNA)、凋亡标记蛋白caspase-3和caspase-9以及炎症因子IL-4、IL-10、IL-13、IL-6、IL-1β和TNF-α的表达。结果:造模组海马组织5-HT的浓度和5-HT1A受体表达远低于假手术组( P <0.01),治疗组海马组织5-HT的浓度和5-HT1A受体表达高于造模组( P <0.05);造模组神经胶质细胞活力远远低于假手术组( P <0.001)。治疗组神经胶质细胞活力显著升高( P <0.01);造模组神经胶质细胞凋亡率远高于假手术组( P <0.001)。治疗组细胞凋亡率显著低于造模组( P <0.01);与假手术组相比,造模组增殖标记蛋白Ki-67 和PCNA及抗炎因子IL-4、IL-10和IL-13的相对表达量大大减少;凋亡标记蛋白caspase-3 和caspase-9及促炎因子IL-6、IL-1β和TNF-α的相对表达量明显升高( P <0.05);与造模组相比,治疗组增殖标记蛋白Ki-67 和PCNA及抗炎因子造模组IL-4、IL-10和IL-13的相对表达量明显增加;凋亡标记蛋白caspase-3 和caspase-9及促炎因子IL-6、IL-1β和TNF-α的相对表达量明显降低( P <0.05)。结论:人参皂苷Rg1在抑郁症中可通过抗细胞凋亡起到神经保护的作用,并通过调控炎症因子的表达来发挥抗炎作用。

Objective: Depression is the fourth most serious disease after cardiovascular disease,diabetes and tumor.Depression seriously damages the quality of people′s lives.The study aims to explore the anti-inflammatory and neuroprotective function of ginsenoside Rg1 and related mechanism in the olfactory bulbectomized rat model of depression. Methods: Rats were divided into 3 groups:control group,model group,treatment group.The olfactory bulbectomized depression model was conducted by surgery.Treatment group rats were given by gavage with ginsenoside Rg1 after surgery.The concentration of 5-hydroxytrypta mine(5-HT) of hippocampus was detected through high performance liquid chromatography.CCK-8 assay was used to test cell viability.Cell apoptosis was detected by flow cytometry.The expression of 5-HT1A receptor,proliferation marker protein antigen identified by monoclonal antibody(Ki-67) and proliferating cell nuclear antigen(PCNA),apoptosis marker protein caspase-3 and caspase-9,inflammatory factors IL-4,IL-10,IL-13,IL-6,IL-1β and tumor necrosis factor alpha(TNF-α) was tested by Western blot. Results: The concentration of 5-HT and the expression of 5-HT1A in model group were lower than the control group( P <0.01).The concentration of 5-HT and the expression of 5-HT1A in treatment group were higher than model group( P <0.05).Compared with the control group,cell viability in model group was largely decreased with enhancive apoptosis( P <0.001).Compared with model group,cell viability in treatment group was obviously increased with reductive apoptosis( P <0.01).Compared with the control group,the expression of Ki-67,PCNA,IL-4,IL-10 and IL-13 in model group was attenuated with elevated expression of caspase-3,caspase-9,IL-6,IL-1β and TNF-α( P <0.05).Compared with model group,the expression of Ki-67,PCNA,IL-4,IL-10 and IL-13 intreatment group was increased and the expression of caspase-3,caspase-9,IL-6,IL-1β and TNF-α was decreased( P <0.05). Conclusion: The neuroprotective function of ginsenoside Rg1 was performed by regulating the expression of inflammatory factors and alleviating nerve cell damage.