β-蜕皮甾酮对MPTP诱导的帕金森病的体内保护研究

In vivo protection study ofβ-ecdysterone against MPTP-induced Parkinson’s disease

目的探讨β-蜕皮甾酮通过激活PI3K/Akt通路对MPTP诱导的帕金森病(PD)小鼠体内神经保护作用。方法将42只小鼠采用随机数字表法分为正常组(A组),模型组(B组),司来吉兰组(C组),β-蜕皮甾酮高(D组)、中(E组)、低剂量组(F组),每组7只。观察行为学变化,Western blot检测脑内TH、PI3K和P-PI3K、Akt和P-Akt、BAX及BCL-2蛋白表达,RT-qPCR检测小鼠脑内BAX、BCL-2 mRNA表达。结果B组小鼠爬杆时间长于A组,C、D、E组小鼠爬杆时间短于B组,差异有统计学意义(P<0.05)。B组小鼠悬挂评分高于A组,C、D、E组小鼠悬挂评分低于B组,差异有统计学意义(P<0.05)。B组P-PI3K/PI3K及P-PAkt/Akt比值低于A组,C、D、E组P-PI3K/PI3K及P-PAkt/Akt比值高于B组,差异有统计学意义(P<0.05)。B组抑凋亡蛋白BCL-2表达低于A组,促凋亡蛋白BAX表达高于A组,差异有高度统计学意义(P<0.01);C、D、E组BCL-2蛋白表达高于B组,BAX蛋白表达低于B组,差异有统计学意义(P<0.05)。B组BCL-2 mRNA表达量低于A组,C、D、E组BCL-2 mRNA表达量高于B组,差异有统计学意义(P<0.05)。B组BAX mRNA表达量高于A组,C、D、E组BAX mRNA表达量低于B组,差异有统计学意义(P<0.05)。结论β-蜕皮甾酮以剂量依赖式激活PI3K/Akt通路保护MPTP诱导的PD小鼠的多巴胺能神经元,继而减弱细胞凋亡。

Objective To investigate the in vivo neuroprotective effect ofβ-ecdysterone on MPTP(MPTP)-induced Parkinson’s disease(PD)mice through activation of the PI3K/Akt pathway.Methods Forty-two mice were divided into normal group(group A),model group(group B),sregiline group(group C),β-ecdysterone high group(group D),medium group(group E),and low dose(group F)group by random number table method,with seven mice in each group.Behavioral changes were observed,TH,PI3K,and P-PI3K,Akt and P-Akt,BAX,and BCL-2 protein expression in the brain were detected by Western blot,and BAX and BCL-2 mRNA expression in the brain of mice were detected by RT-qPCR.Results Mice in group B took longer to climb the pole than those in group A,while mice in groups C,D,and E took shorter time to climb the pole than those in group B,and the differences were statistically significant(P<0.05).The suspension scores of mice in group B were higher than those in group A,while the suspension scores of mice in groups C,D,and E were lower than those in group B,and the differences were statistically significant(P<0.05).The P-PI3K/PI3K and P-PAkt/Akt ratios in group B were lower than those in group A,while the P-PI3K/PI3K and P-PAkt/Akt ratios in groups C,D,and E were higher than those in group B,and the differences were statistically significant(P<0.05).The expression of apoptosis-inhibiting protein BCL-2 in group B was lower than that in group A,while the expression of pro-apoptosis protein BAX was higher than that in group A,and the differences were highly statistically significant(P<0.01);the expression of BCL-2 protein in groups C,D,and E were higher than that in group B,while the expression of BAX protein were lower than that in group B,and the differences were statistically significant(P<0.05).The expression of BCL-2 mRNA in group B was lower than that in group A, while the expression of BCL-2 mRNA in groups C, D, and E were higher than that in group B, and the differences were statistically significant (P<0.05). The expression of BAX mRNA in group B was higher than that in group A, while the expression of BAX mRNA in groups C, D, and E were lower than that in group B, and the differences were statistically significant (P<0.05). Conclusion β-Ecdysterone protects dopaminergic neurons in MPTP-induced PD mice with dose-dependent activation of the PI3K/Akt pathway, which subsequently attenuates apoptosis.