首页|电针对帕金森病模型小鼠运动功能的影响及相关分子机制探讨

电针对帕金森病模型小鼠运动功能的影响及相关分子机制探讨

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目的 探究电针对帕金森病(PD)模型小鼠运动功能及中脑黑质NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体相关蛋白的影响。方法 按照随机数字表法将C57BL/6 小鼠分成对照组、模型组、电针组,每组12 只。鱼藤酮溶液10 mg/(kg·d)灌胃小鼠模拟 PD 模型。造模后,电针组选取"风府""太冲""足三里"电针刺激,治疗 2 周;对照组和模型组为控制变量采取同一时间同步固定操作。采用行为学评分并运用旷场实验检测各组小鼠运动能力,免疫组化方法检测各组小鼠中脑黑质酪氨酸羟化酶(TH)和α-突触核蛋白(α-syn)表达,蛋白质印迹法检测小鼠中脑黑质NLRP3、胱天蛋白酶-1(Caspase-1)蛋白表达水平,酶联免疫吸附测定法检测各组小鼠中脑黑质白细胞介素-1β(IL-1β)含量。结果 与对照组比较,模型组小鼠行为学评分升高(P<0。01);与模型组比较,电针组小鼠行为学评分降低(P<0。01)。与对照组比较,模型组小鼠相对静止(速度<100 mm/s)状态时间比升高(P<0。01),运动缓慢(速度 100~200 mm/s)状态、快速运动(速度>200 mm/s)状态时间比降低(P<0。01);与模型组比较,电针组小鼠相对静止状态时间比降低(P<0。01),运动缓慢状态、快速运动状态时间比升高(P<0。01),运动速率提高。与对照组比较,模型组中脑黑质TH表达水平降低(P<0。01),α-syn表达水平升高(P<0。01);与模型组比较,电针组TH表达水平增加(P<0。05),α-syn 表达水平降低(P<0。05)。与对照组比较,模型组中脑黑质NLRP3、Caspase-1 蛋白表达增多(P<0。01);与模型组比较,电针组小鼠中脑黑质NLRP3、Caspase-1表达量减少(P<0。01)。与对照组比较,模型组小鼠中脑黑质IL-1β含量升高(P<0。01);与模型组比较,电针组IL-1β含量降低(P<0。05)。结论 电针刺激"风府""太冲""足三里"能够有效减少PD标志物α-syn的异常聚集,增加TH表达量,改善PD模型小鼠的运动功能障碍,其分子机制可能与调控炎症小体相关通路NLRP3、Caspase-1、IL-1β表达有关。
Effects of electroacupuncture on motor function and related molecular mechanisms in mice with Parkinson's disease
Objective To explore the effects of electroacupuncture on motor function in Parkinson's disease(PD)model mice and NLRP3 inflammasome-related proteins in the midbrain substantia nigra(SN).Methods C57BL/6 mice were assigned to three groups according to the random number table method:control group,model group,and electroacupuncture(EA)group,12 mice per group.The PD model was reproduced by intragastric administration of rotenone solution 10 mg/(kg·d).EA group was administered at the three selected points,"Fengfu"(GV16),"Taichong"(LR3),and"Zusanli"(ST36),with a treatment cycle of 2 weeks.The control and model groups took the same time synchronous fixation operation for the control variable.Behavioral scores and open field tests were used to detect the exercise ability of mice in each group.Tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the midbrain SN of mice in all groups were measured with an immunohistochemistry test.NLRP3 and cysteinyl aspartate specific proteinase-1(Caspase-1)protein expression levels in the midbrain SN of mice in the three groups were measured using Western blotting,and interleukin-1β(IL-1β)content was determined with an enzyme-linked immunosorbent assay.Results Compared to the control group,the behavioral scores of the mice in the model group were higher(P<0.01).Compared to the model group,the behavioral scores of the mice in the EA group were lower(P<0.01).Compared to the control group,the time ratio of the relative rest state of the mice in the model group(<100 mm/s)increased significantly(P<0.01),while the time ratio of the slow motion(100~200 mm/s)and time ratio of the fast motion(>200 mm/s)state decreased significantly(P<0.01).Compared to the model group,the time ratio spent in the relative rest state of mice in the EA group decreased significantly(P<0.01),while the time ratio of the slow motion state and time ratio of the fast motion state and movement rate increased significantly(P<0.01).Compared to the control group,the TH expression level decreased in the SN in the model group(P<0.01),while α-syn increased(P<0.01).Compared to the model group,the TH expression level in the EA group increased(P<0.05),while α-syn decreased(P<0.05).Compared to the control group,the protein expressions of NLRP3 and Caspase-1 in the SN of the model group increased(P<0.01);compared to the model group,the expressions of NLRP3 and Caspase-1 in the SN of the midbrain of mice decreased after EA treatment(P<0.01).Compared to the control group,IL-1β in the SN of the mouse midbrain increased in the model group(P<0.01).Compared to the model group,IL-1β decreased in the EA group(P<0.05).Conclusion This experiment shows that stimulation of EA in"Fengfu","Taichong",and"Zusanli"can effectively reduce abnormal aggregation of the PD marker α-syn,increase TH expression,and enhance the motor dysfunction of PD model mice.The molecular mechanism is related to the regulation of the expression of NLRP3,Caspase-1,and IL-1β of inflammasome-related pathways.

Parkinson's diseaseelectroacupuncturemotor dysfunctionFengfu(GV16)Taichong(LR3)Zusanli(ST36)mice

祁羚、李亚楠、汪瑶、张小蕾、胡梦妮、李含章、肖蝶、荣臻、马骏

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湖北中医药大学针灸骨伤学院 武汉 430060

湖北时珍实验室

帕金森病 电针 运动功能障碍 风府 太冲 足三里 小鼠

国家自然科学基金中国博士后科学基金

814737882023M741110

2024

北京中医药大学学报
北京中医药大学

北京中医药大学学报

CSTPCD北大核心
影响因子:1.568
ISSN:1006-2157
年,卷(期):2024.47(5)