Fas/FasL信号通路与帕金森病大鼠多巴胺能神经元的相关性研究

Correlation between Fas/FasL Signaling Pathway and Dopaminergic Neurons in Rats with Parkinson's Disease

背景免疫炎症可能是导致帕金森病(PD)的因素,而Fas/FasL信号通路诱导的淋巴细胞凋亡与心血管疾病、自身免疫系统疾病的发生及预后均密切相关。目的探讨Fas/FasL信号通路与PD大鼠多巴胺能神经元的相关性。方法2017年10月—2018年1月,从60只雄性SPF级SD大鼠随机选取10只作为对照组,其余大鼠采用脑立体定位技术建立PD大鼠模型,并将建模成功的20只大鼠随机分为模型组与干预组,每组10只。对照组、模型组大鼠给予0.9%氯化钠溶液2 ml灌胃,干预组大鼠则给予美多芭溶液2 ml灌胃,均为1次/d,连续灌胃14 d。比较模型组与干预组大鼠干预后阿扑吗啡(APO)诱导的旋转圈数,并比较三组大鼠脑组织Fas、FasL、酪氨酸氢化酶(TH)蛋白表达水平;TH蛋白表达水平与PD大鼠Fas、FasL蛋白表达水平的相关性采用Pearson相关分析。结果干预组大鼠干预后APO诱导的旋转圈数少于模型组(P<0.05)。对照组与干预组大鼠的Fas、FasL蛋白表达水平低于模型组,TH蛋白表达水平高于模型组(P<0.05);干预组大鼠的Fas、FasL蛋白表达水平高于对照组,TH蛋白表达水平低于对照组(P<0.05)。Pearson相关分析结果显示,TH蛋白表达水平与Fas、FasL蛋白表达水平无直线相关性(r值分别为0.053、0.026,P>0.05)。结论PD大鼠Fas、FasL蛋白表达水平较高,Fas/FasL信号通路激活,但多巴胺能神经元数量较少,且Fas/FasL信号通路与PD大鼠多巴胺能神经元无直线相关关系。

Background Immune inflammation is a possible factor of Parkinson's disease,however Fas/FasL signaling pathway-induced lymphocyte apoptosis is closely correlated with the occurrence and prognosis of cardiovascular disease and autoimmune system disease.Objective To investigate the correlation between Fas/FasL signaling pathway and dopaminergic neurons in rats with Parkinson's disease.Methods From October 2017 to January 2018,10 out of 60 male SPF SD rats were randomly selected as control group,while the other 50 rats were used to prepare for Parkinson's disease models by stereotactic brain technology,after that 20 rats with successful preparation for Parkinson's disease models randomly divided into model group(n=10)and intervention group(n=10).Rats in control group and model group received intragastric administration of 0.9%sodium chloride solution(2 ml per time,1 time per day)for 14 days,while rats in intervention group received intragastric administration of Madopar solution(2 ml per time,1 time per day)for 14 days.APO-induced number of rotations was compared between model group and intervention group after intervention,meanwhile protein expression levels of Fas,FasL and tyrosine hydrogenase(TH)in brain tissue were compared among the three groups after intervention;Pearson correlation analysis was used to analyze the correlations of protein expression level of TH with protein expression levels of Fas and FasL.Results APO-induced number of rotations in intervention group was statistically significantly less than that in model group after intervention(P<0.05).Protein expression levels of Fas and FasL in brain tissue in control group and intervention group were statistically significantly lower than those in model group after intervention,while protein expression level of TH in brain tissue in control group and intervention group was statistically significantly higher than that in model group,respectively(P<0.05);protein expression levels of Fas and FasL in brain tissue in intervention group were statistically significantly higher than thsoe in control group after intervention,while protein expression level of TH in brain tissue in intervention group was statistically significantly lower than that in control group(P<0.05).Pearson correlation analysis results showed that,protein expression level of TH was not linearly correlated protein expression level of Fas(r=0.053)or FasL(r=0.026)in rats with Parkinson's disease(P>0.05).Conclusion Protein expression levels of Fas and FasL are significantly high and Fas/FasL signaling pathway is activated in rats with Parkinson's disease,but the number dopaminergic neurons is relatively,moreover Fas/FasL signaling pathway is not linearly correlated the number dopaminergic neurons in rats with Parkinson's disease.