摘要
目的观察熟地平颤颗粒对帕金森病大鼠行为学及黑质内α-突触核蛋白(α-syn)表达的影响。方法采用6-羟基多巴胺(6-OHDA)注射于大鼠脑右侧黑质造成偏侧帕金森病(PD)模型。实验设立正常对照组、帕金森病模型组、左旋多巴(LD)组、LD+中药(TCM)组,治疗4周后观察各组大鼠旋转圈数、旋转持续时间以及异常不自主运动(AIM)评分的变化;采用RT-PCR方法检测大鼠黑质内α-syn基因表达情况;免疫组织化学法检测黑质内α-syn、TH蛋白的表达情况。结果与治疗前比较,PD组大鼠旋转圈数差异无统计学意义(P>0.05),旋转持续时间较治疗前缩短(P<0.05)。与同期PD组比较,LD组第7天、第14天的旋转圈数旋转持续时间均低于PD组,第28天的评分高于PD组(P<0.05);与同期LD组比较,LD+TCM组自第21天起的旋转圈数、旋转持续时间评分显著降低(P<0.05)。LD组大鼠用药后第14天起的AIM评分逐步增高(P<0.01);LD+TCM组治疗前后AIM评分差异无统计学意义。PD组与正常对照组比较α-synmRNA表达增高,Levodopa组与PD组比较,α-synmRNA明显增高,LD+TCM组较LD组α-synmRNA表达显著降低(P<0.05)。免疫组化结果显示:PD组较正常对照组α-syn表达增加s TH表达降低;LD组与PD组比较,α-syn表达增加s TH表达降低;LD+TCM组与LD组比较,α-syn表达降低s TH表达增加(P<0.01)。结论长期使用左旋多巴可以引起α-syn过表达,进一步加重中脑黑质区的神经损伤,造成行为学症状恶化。熟地平颤颗粒结合左旋多巴治疗PD有明显的增效减毒作用,中药通过抑制α-syn的过表达,减少了黑质多巴胺能细胞的损伤,有效缓解了帕金森病症状。
Objective To observe the effect of Shudi Pingchan granule （SPG） on behavior and α- synuclein （α syn） expression in substantia nigra in rats with Parkinson＇s disease （PD）. Methods The rat model of hemiparkinsonian was established by injecting 6 -hydroxydopamine （6- OHDA） into substantia nigra of right brain. Then,the rats were divided into normal control group,PD group, levodopa （LD） group,and LD plus SPG group. After 4 weeks of treatment,the number of turns,total duration of turning and abnormal involuntary movement （AIM） scores were observed. The gene expression of α-synuclein was detected by real- time polymerase chain reaction （RT- PCR）. The protein expression of α-syn and TH was detected by immunohistochemistry. Results The number of turns in PD group had no significant difference compared with that before treatment（ P 〉0.05） ,and total duration of turning short-ened （ P 〈0.05） .The total duration of turning in LD group on the 7th and 14th day were lower than those in PD group in the same time,but they were higher than those in PD group on the 28th day（P〈0.05）. The number of turns and total duration of turning in LD ＋ TCM group was significantly lower than those of PD group since the 14th day（ P 〈0.05）. The AIMs of LD group increased graduallysince the 14th day（ P 〈0.01）. The scores of AIM in LD plus SPG group had no difference compared with that before treatmentC P 〉0.05）. Compared with normal control group,α-syn mRNA expression increased significantly in PD group.Compared with PD group,-syn mRNA significantly increased in LD group. The expression of α- syn mRNA in LD plus SPG group decreased obviously compared with LD group （ P 〈0.05）. Compared with the normal control group,α-syn expression increased and TH expression reduced in PD group. Compared with PD group,α-syn expression increased and TH expression decreased in LD group. Compared with LD group, a syn expression decreased and TH expression increased in LD plus SPG group （ P 〈0.01） .Conclusion Long- term use of LD can cause over expression of α-syn and further aggravatenerve damage in midbrain nigra,which makes the behavioral symptoms worse. SPG and LD treating PD has effect on apparente synergia and attenuation. SPG can effectively alleviate the symptoms of PD by inhibiting over- expression of α-syn, reducing the damage of dopaminergic cells.
出处
《中西医结合心脑血管病杂志》
2017年第4期419-424,共6页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
国家自然科学基金面上项目(No.81673726)
国家自然科学基金青年项目(No.81302926)
上海市科委重大项目(No.15401970100)
上海市卫计委杏林新星人才计划项目(No.ZY3-RCPY-2-2005)
关键词
帕金森病
熟地平颤颗粒
行为学
Α-突触核蛋白
增效减毒
Parkinson＇s disease
Shudi Pingchan granule
behavior
α-synuclein
apparente synergia and attenuation
