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目的:研究葛根素对6-羟多巴胺(6-OHDA)致帕金森病(PD)大鼠黑质组织核转录因子(Nrf2)/抗氧化反应元件(ARE)通路的影响。方法:建立帕金森SD大鼠模型,随机分成5组:模型组、美多巴阳性组(40 mg.kg-1)及葛根素低、中、高剂量组(20,40,80 mg.kg-1)。持续灌胃给药30 d。Elisa法检测黑质组织中γ-谷氨酰半胱氨酸合成酶(γ-GCS)、谷胱甘肽(GSH)、过氧化氢酶(CAT)活性。RT-PCR法检测黑质组织细胞色素c氧化酶(COX)mRNA表达。Western blot法检测转录因子NF-E2相关因子2(Nrf2)、Kelch样环氧氯丙烷相关蛋白-1(Keapl)蛋白表达。结果:与正常组比较,模型组黑质中r-GCS,GSH,CAT活性显著降低,COX mRNA Nrf2,Keapl蛋白表达显著降低(P<0.01);与模型组比较,葛根素有效地增加帕金森病大鼠黑质γ-GCS,GSH,CAT活性(P<0.01)。葛根素低,中,高剂量组能明显上调黑质COX mRNA水平(38.5±4.3)%,(43.2±5.1)%,(57.4±6.2)%(P<0.01),显著增加Nrf2,Keapl蛋白表达(38.5±3.6)%,(52.4±4.8)%,(78.5±7.3)%;(31.7±2.3)%,(40.8±3.5)%,(65.9±6.1)%(P<0.01)。结论:葛根素有效地对抗6-OHDA诱导PD大鼠黑质神经细胞氧化应激性损伤,其机制可能与其调节Nrf2/ARE通路有关。
Objective: To study the effects of puerarin on the nuclear factor (Nrf2) / antioxidant element (ARE) pathway in the substantia nigra of Parkinson’s disease (PD) induced by 6-hydroxydopamine (6-OHDA) Methods: A rat model of Parkinson’s disease was established and randomly divided into 5 groups: model group, mepbabine positive group (40 mg.kg-1) and puerarin low, medium and high dose groups (20, 40 and 80 mg.kg -1). Continuous oral administration of 30 d. Elisa method was used to detect the activity of γ-glutamylcysteine synthetase (GSH) and catalase (CAT) in substantia nigra. The mRNA expression of cytochrome c oxidase (COX) in substantia nigra was detected by RT-PCR. Western blot was used to detect the expression of NF-E2 related factor 2 (Nrf2) and Kelch-like epichlorohydrin-related protein-1 (Keapl). Results: Compared with the normal group, the activities of r-GCS, GSH and CAT in the substantia nigra of model group decreased significantly and the expression of Nrf2 and Keapl protein in COX mRNA decreased significantly (P <0.01). Compared with model group, puerarin effectively increased Parkinson’s The activity of γ-GCS, GSH and CAT in the substantia nigra of the diseased rats (P <0.01). Puerarin significantly increased the expression of Nrf2 and Keap1 protein in substantia nigra (38.5 ± 4.3)%, (43.2 ± 5.1) and (57.4 ± 6.2)% (P <0.01) (38.5 ± 3.6)%, (52.4 ± 4.8)%, (78.5 ± 7.3)%, (31.7 ± 2.3)%, (40.8 ± 3.5)%, (65.9 ± 6.1)%, respectively. CONCLUSION: Puerarin is effective against 6-OHDA-induced oxidative stress injury of substantia nigra neurons in PD rats, which may be related to the regulation of Nrf2 / ARE pathway.