【摘要】 目的研究Salubrinal通过抑制内质网应激减轻帕金森小鼠神经损伤的机制。方法将36只C57BL/6雄性小鼠随机分为对照组、模型组和实验组,每组12只。模型组予以腹腔注射30 mg·kg^-1 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）,每天1次,连续7 d,诱导帕金森病模型。对照组予以腹腔注射等量的0. 9%Na Cl,每天1次,连续7 d;实验组予以腹腔注射MPTP,方法同模型组,在给予MPTP后立即予以腹腔注射1 mg·kg^-1 Salubrinal治疗,每天1次,连续7 d。通过悬挂实验、爬杆实验和胶布移除实验观察小鼠的行为学能力,用免疫组化法观察小鼠黑质酪氨酸羟化酶阳性细胞的变化,用免疫印记检测小鼠黑质葡萄糖调节蛋白78（GRP78）和环腺苷酸反应元件结合转录因子同源蛋白（CHOP）的表达。结果与模型组相比,实验组小鼠在第5天时,其爬下时间减少6. 7%（P <0. 05）,悬挂实验打分增加28. 9%（P <0. 05）,胶布移除时间减少16. 6%（P <0. 05）;在第7天时,其转向时间和爬下时间分别减少20. 2%和5. 8%（均P <0. 05）,悬挂实验打分增加79. 0%（P <0. 05）,胶布移除时间减少6. 1%（P <0. 05）。同时,Salubrinal还能拮抗MPTP所致小鼠中脑酪氨酸羟化酶阳性神经元减少,下调黑质GRP78和CHOP的表达,与模型组比,实验组小鼠中脑的酪氨酸羟化酶阳性神经元数量增多63. 4%（P <0. 05）; GRP78和CHOP的表达分别下降15. 8%和42. 3%（均P <0. 05）。结论 Salubrinal可以通过抑制内质网应激减轻MPTP诱导的小鼠黑质多巴胺能神经元的凋亡。更多还原

【Abstract】 Objective To investigate the neuroprotective effect of Salubrinal on neuronal injury induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride（ MPTP） through inhibiting endoplasmic reticulum stress（ ERS） in Pakinson’s disease mice. Methods Thirty six male C57 BL/6 mice were randomly divided into control group,model group and experimental group with 12 cases in each group. Mice of model group were intraperitoneally injected with MPTP( 30 mg·kg^-1·d^-1,7 days) to construct Parkinson’s disease model. Experimental group was given 1 mg·kg^-1·d^-1 Salubrinal following MPTP,intraperitoneally injected and control groups were given equivalent normal saline for 7 days. Then behavior was assessed using the traction test,pole test and adhesive removal. Additionally,the changes of tyrosine hydroxylase（ TH） were evaluated by immunohistochemical staining. Glucose regulated protein 78（ GRP78） and C/EBP homologous protein（ CHOP） were measured by Western blot in the substantia nigra. Results Compared to model group,at the fifth day the climbing total time（ T-total） shortened by 6. 7%（ P < 0. 05） and the suspension test score increased by 28. 9%（ P < 0. 05） and adhesive removal time decreased by 16. 6%（ P < 0. 05） in experimental group; at the seventh day,T-total and T-turn shortened by 20. 2% and 5. 8%（ all P < 0. 05）,respectively,and the suspension test score increased by 79. 0%（ P < 0. 05） and adhesive removal time decreased by 6. 1%（ P < 0. 05） in experimental group. Meanwhile,Salubrinal could significantly rescue TH-positive cells reduced by MPTP and down-regulate the expression of GRP78 and CHOP in the midbrain. Compared to model group,TH-positive cells increased by 63. 4%（ P < 0. 05）; GRP78 and CHOP decreased by 15. 8% and 42. 3%（ all P < 0. 05） respectively. Conclusion All these effects indicate that Salubrinal can alleviate MPTP-induced apoptosis of dopaminergic neurons in substantia nigra of mice by inhibiting sthe ERS.更多还原