依达拉奉对帕金森病小鼠模型中脑细胞自噬相关蛋白表达的影响

Effect of edaravone on the expression of autophagy related proteins in midbrain cell of parkinson's disease mice model

目的研究依达拉奉对帕金森病(PD)小鼠模型中脑细胞自噬相关蛋白表达的影响。方法将42只C57BL/6雄性小鼠被随机分为对照组、模型组及实验组,各14只。模型组及实验组小鼠均腹腔注射25 mg·kg^(-1)1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)建立PD小鼠模型,对照组则腹腔注射等量生理盐水;建模成功后实验组腹腔注射3 mg·kg^(-1)依达拉奉,对照组及模型组则腹腔注射等量生理盐水,连续干预2周。以爬杆实验及悬挂实验对比小鼠行为学变化;用免疫组化法检测中脑黑质脑组织自噬相关蛋白表达情况。结果与对照组比较,模型组小鼠干预后1,2周爬杆时间均延长,悬挂实验评分降低(P<0.01);与模型组比较,实验组小鼠干预后1,2周爬杆时间均缩短,悬挂实验评分升高(P<0.01)。免疫组化显示,干预后2周,对照组、模型组及实验组小鼠中脑黑质脑组织Beclin1阳性细胞比例分别为(7.04±1.98)%,(27.05±2.01)%,(16.46±1.87)%;微管相关蛋白轻链3(LC3)阳性细胞比例分别为(5.41±1.67)%,(21.26±1.51)%,(14.86±1.49)%。与对照组比较,干预后1,2周模型组小鼠中脑黑质脑组织Beclin1及LC3阳性细胞比例明显增多(P<0.01);而实验组Beclin1及LC3阳性细胞比例较模型组明显降低(P<0.01)。结论依达拉奉可有效抑制PD小鼠中脑黑质脑组织细胞自噬相关蛋白Beclin1及LC3表达,改善PD小鼠异常行为。

Objective To explore the effect of edaravone on the expression of autophagy related proteins in midbrain cell of parkinson＇s disease（ PD） model mice. Methods Forty-two cases of C57 BL/6 male mice were randomly divided into control group,model group and test group,14 cases in each group. Model group and test group were intraperitoneally（ ip） injected 25 mg·kg^-1 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（ MPTP） to construct PD model mice,control group was ip equivalent normal saline. After successfully built PD model mice,test group was ip 3 mg·kg^-1 edaravone,control group and model group were ip equivalent normal saline,and each group was intervened for 2 weeks continuously. The changes of mice behavior were detected by climbing pole test and suspension test; the expression of autophagy related proteins in midbrain substantia nigrabrain tissue were detected by immunohistochemistry. Results Compared with control group,1 and 2 weeks afterintervention,the climbing pole time lengthened and the suspension test score decreased in model group（ P〈0. 01）.Compared with model group,1 and 2 weeks after intervention,the climbing pole time shortened and the suspension test score increased in test group（ P〈0. 01）. Immunohistochemistry showed that,the Beclin1 positive cells proportion of mice midbrain substantia nigrabrain tissue at 2 weeks after intervention in control group,model group and test group were（ 7. 04 ± 1. 98） %,（ 27. 05 ± 2. 01） %,（ 16. 46 ± 1. 87） %; and the microtubule associated protein light chain3（ LC3） positive cells proportion were（ 5. 41 ± 1. 67） %,（ 21. 26 ± 1. 51） %,（ 14. 86 ± 1. 49） %. Compared with control group,1 week and 2 weeks after intervention,the Beclin1 and LC3 positive cells proportion in model group increased（ P〈0. 01）; while the Beclin1 and LC3 positive cells proportion in test group decreased compared with model group（ P〈0. 01）. Conclusion Edaravone can inhibit effectively the expression of midbrain substantia nigrabrain tissue autophagy related proteins Beclin1 and LC3,and improve the abnormal behavior of PD model mice.