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目的观察老龄和脂多糖(LPS)刺激二次打击致小鼠PD模型脑组织中组蛋白去乙酰化酶1(Sir T1)和胶质细胞源性神经生长因子(GDNF)的表达水平。方法 C57BL/6小鼠随机分为老年LPS-PD组(n=8)、青年LPS-PD组(n=8)、老年对照组(n=8)、青年对照组(n=8)。PD模型制作:LPS 20μL(1μg·μL~(-1)),两侧鼻孔滴入,隔日1次,共60 d。对照组用等量生理盐水滴鼻。采用动物行为学爬竿实验测定小鼠行为变化。Western blot检测小鼠脑组织中酪氨酸羟化酶(TH)、Sir T1和GDNF表达,免疫组织荧光法检测黑质纹状体区TH表达,分析老龄和LPS刺激作用下多巴胺神经元丢失与Sir T1、GDNF表达量的变化。结果与青年对照组比较,老年LPS-PD组爬竿实验时间延长最为显著,TH、GDNF和SirT1表达下降最为显著(P<0.01);老年对照组和青年LPS-PD组运动时间显著延长,TH、SirT1表达显著下降(P<0.05),Sir T1表达与TH表达呈正相关性。青年LPS-PD组GDNF表达显著高于青年对照组(P<0.05)。老龄和LPS二次打击作用均可导致多巴胺神经元显著丢失,运动协调能力下降。脑内GDNF和SirT1表达量随年龄增长而下降,与多巴胺神经元丢失相平行;但青年LPS-PD组GDNF呈代偿性高表达。结论老龄和LPS二次打击下PD模型多巴胺神经元的丢失可能与GDNF和Sir T1神经保护因子表达下降有一定相关性。
Objective To investigate the expressions of Sir T1 and glial cell line-derived nerve growth factor (GDNF) in the brain of mice with secondary model induced by lipopolysaccharide (LPS). Methods C57BL / 6 mice were randomly divided into three groups: old LPS-PD group (n = 8), young LPS-PD group (n = 8), aged control group (n = 8) and young control group (n = 8). PD model: LPS 20μL (1μg · μL -1), both sides of the nose drip, every other day, a total of 60 d. The control group with the same amount of saline drip nose. The animal behavioral climbing pole experiment was used to determine the behavioral changes in mice. Western blot was used to detect the expression of tyrosine hydroxylase (TH), Sir T1 and GDNF in brain tissue of mice, the expression of TH in nigrostriatum was detected by immunohistochemistry, and the loss of dopamine neurons Sir T1, GDNF expression changes. Results Compared with the young control group, the prolongation of the pole-climbing experiment in the elderly LPS-PD group was the most significant, the expression of TH, GDNF and SirT1 was the most significant decrease (P <0.01); the exercise time was significantly longer in the elderly control group and the youth LPS-PD group, , SirT1 expression was significantly decreased (P <0.05), Sir T1 expression and TH expression was positively correlated. GDNF expression in young LPS-PD group was significantly higher than that in young control group (P <0.05). Old age and LPS secondary attack can lead to significant loss of dopaminergic neurons, motor coordination decreased. The expression of GDNF and SirT1 in brain decreased with age and was parallel to the loss of dopaminergic neurons. However, the expression of GDNF in young LPS-PD group was highly compensatory. Conclusions The loss of dopamine neurons in PD model under aging and LPS secondary challenge may be related to the decrease of the expression of GDNF and Sir T1 neuroprotective factors.