白藜芦醇诱导细胞外调节蛋白激酶信号通路以缓解帕金森病神经元损伤的研究

Research on extracellular regulatory protein kinase signaling pathway induced by resveratrol in alleviating neuronal damage in Parkinson's disease

目的研究白藜芦醇通过调节细胞外调节蛋白激酶(ERK)信号通路缓解帕金森病(PD)神经元损伤的作用。方法取40只雄性Wistar大鼠用6-羟多巴胺诱导,构建大鼠帕金森模型,并随机分为模型组和实验组,每组20只。另取,20只雄性Wistar大鼠作为对照组。实验组予以20 mg·kg^(-1)·d^(-1)白藜芦醇,模型组和对照组予以20 mg·kg^(-1)·d^(-1)0.9%Na Cl。3组大鼠连续灌胃14 d。观察大鼠旋转行为学改变,用免疫组化法检测大鼠酪氨酸羟化酶含量,用TUNEL法检测神经细胞凋亡,用Western blot法检测ERK、核转录因子κB(NF-κB)和半胱氨酸天冬氨酸蛋白水解酶3(Caspase 3)蛋白的表达。结果治疗后,实验组、模型组、对照组的30 min平均旋转圈数分别为(104.81±6.64),(187.56±7.32)和(1.37±0.45)圈,酪氨酸羟化酶分别为(0.83±0.04),(0.71±0.06)和(1.00±0),细胞凋亡数分别为(18.23±1.47),(32.84±1.86)和(11.58±1.24)个,ERK蛋白含量分别为(1.57±0.07),(1.14±0.05)和(1.32±0.07),NF-κB蛋白含量分别为(0.86±0.04),(1.08±0.06)和(0.79±0.03),Caspase 3蛋白含量分别为(0.68±0.03),(0.87±0.04)和(0.59±0.02),实验组的上述指标与对照组和模型组比较,差异均有统计学意义(均P<0.05)。结论白藜芦醇可通过调节ERK信号通路来缓解帕金森病大鼠的神经元损伤。

Objective To investigate the effect of resveratrol by regula- ting the extracellular regulatory protein kinase （ERK） signaling pathway to alleviate neuronal damage in Parkinson＇ s disease （PD） and its protec- tive mechanism. Methods Forty male Wistar rats were induced with 6 - hydroxydopamine to construct Parkinson＇ s model, and they were ran- domly divided into model group and test group with 20 cases per group. Another 20 male Wistar rats were used as control group. Test group was given 20 mg kg-1·d-1 resveratrol, model and control groups were given 20 kg-1·d-1,0. 9%NaC1. Three groups were treated for 14 d with gavage. The changes of rotation behavior were observed between three groups. The levels of tyrosine hydroxylase were measured by immu- nohistochemistry. The levels of neuron apoptosis were measured by TUNEL method. The expression levels of ERK, nuclear factor - KB （NF- KB） and cysteinyl aspartate specific proteinase 3 （Caspase 3 ）were measured by Western blot. Results After treatment, the main indexes in test, model and control groups were compared ： the average number of revolutions in 30 rain wee （ 104. 81 ± 6. 64 ） , （ 187.56 ± 7.32） , （ 1. 37 ± 0. 45 ） cycles; tyrosine hydroxylase were （0.83 ± 0.04）, （0.71 ± 0.06）, （1. 00 ± 0）; neuron apoptosis were （18.23±1.47）, （32.84±1.86）, （11.58±1.24） number ; ERK protein were （1. 57±0.07）, （1. 14±0.05）, （ 1. 32 ± O. 07 ） ; NF - KB protein were （ 0. 86 ± 0.04 ）, （ 1. 08 ± O. 06 ）, （ 0. 79 ± O. 03 ） ; Caspase 3 protein were （0. 68 ± 0. 03 ）, （0. 87 ± 0. 04）, （0. 59 ± 0. 02）, the differences were statistically significant between test group and control, model groups（ P 〈 0.05）. Conclusion Resveratrol can relieve neuronal damage in Parkinson＇ s disease rats by regulating ERK signaling pathway.