姜黄素对帕金森病模型小鼠的神经保护作用及其机制

The neuroprotective effect of curcumin in a mouse model of Parkinson’s disease and its mechanism

目的探究姜黄素对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(Parkinson disease,PD)模型小鼠的神经保护作用及其机制。方法将72只雄性C57BL/6J小鼠,随机分为Control组(A组)、MPTP组(B组)和MPTP+姜黄素组(C组)。实验前5 d,B、C组小鼠每天腹腔注射MPTP 30 mg/kg,A组小鼠腹腔注射等量生理盐水;第6天始,C组小鼠每天腹腔注射姜黄素(溶于DMSO)50 mg/kg,A、B组小鼠每天腹腔注射等量的DMSO,连续7 d。给药结束后,采用行为学实验评估各组小鼠的运动、学习和记忆力功能。实验第15天,取各组小鼠黑质区,ELISA法检测TNF-α、IL-1β和IL-6的含量,蛋白印迹法检测CD86和NF-κB的相对含量,荧光免疫组织化学染色检测TH阳性神经元的数量。结果与B组相比,A、C组小鼠的下降时间明显减少,脱落潜伏期和交替百分比明显增加(F=17.29~19.28,P<0.05),黑质中TNF-α、IL-1β和IL-6的含量明显减少(F=31.73~80.97,P<0.05),黑质中CD86、NF-κB蛋白的表达明显减少(F=24.93、55.61,P<0.05),黑质中TH阳性神经元的数量显著增加(F=47.64,P<0.05)。结论姜黄素可有效改善PD模型小鼠的行为障碍,发挥神经保护作用,其机制可能与抑制NF-κB信号通路,致小胶质细胞活化抑制、炎性反应发生降低、多巴胺能神经元退化减轻有关。

Objective To investigate the neuroprotective effect of curcumin on mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease(PD)and its mechanism.Methods A total of 72 male C57BL/6J mice were randomly divided into control group(group A),MPTP group(group B),and MPTP+curcumin group(group C).For the 5 d before the experiment,the mice in groups B and C were given intraperitoneal injection of MPTP every day,and those in group A were given intraperitoneal injection of an equal volume of normal saline;since day 6,the mice in group C were given intraperitoneal injection of curcumin dissolved in DMSO at a dose of 50 mg/kg,and those in groups A and B were given intraperitoneal injection of an equal volume of DMSO,every day for 7 consecutive days.After the end of administration,behavioral experiments were used to evaluate the motor,learning,and memory functions of mice in each group.On day 15 of the experiment,the samples of substantia nigra were collected from the mice in each group,and ELISA was used to measure the content of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6);Western blotting was used to measure the relative content of CD86 and NF-κB;immunohistochemical staining was used to measure the number of TH-positive neurons.Results Compared with group B,groups A and C had a significant reduction in descending time,significant increases in drop latency and percentage of alternation(F=17.29-19.28,P<0.05),significant reductions in the content of TNF-α,IL-1β,and IL-6(F=31.73-80.97,P<0.05)and the expression of CD86 and NF-κB in the substantia nigra(F=24.93,55.61,P<0.05),and a significant increase in the number of TH-positive neurons in the substantia nigra(F=47.64,P<0.05).Conclusion Curcumin can effectively improve behavior disorder and exert a neuroprotective effect in PD mice,possibly by inhibiting the NF-κB signaling pathway,thereby leading to the inhibition of microglial cell activation,the reduction in inflammatory response,and the alleviation of dopaminergic neuron degeneration.