神经妥乐平通过Nrf2/HO-1/NQO1通路发挥对帕金森病大鼠的神经保护作用

目的探讨神经妥乐平对帕金森病(PD)大鼠的神经保护作用及其相关机制。方法 SD大鼠分为对照组、PD组(PD造模)、神经妥乐平低剂量组(PD造模+腹腔注射0.6 Nu·kg^-1神经妥乐平溶液)、神经妥乐平高剂量组(PD造模+腹腔注射1.2 Nu·kg^-1神经妥乐平溶液)和通路抑制组(PD造模+腹腔注射1.2 Nu·kg^-1神经妥乐平溶液及2 mg·k^-1 Nrf2通路抑制剂Brusatol)。转棒试验及爬杆试验测试大鼠的行为功能,记录跌落潜伏期、爬下时间;苏木精-伊红染色观察脑组织病理变化;试剂盒检测脑组织中过氧化氢酶(CAT)活性、丙二醛(MDA)含量及白细胞介素(IL)-6、IL-1β水平;蛋白印迹检测脑组织中核因子E2相关因子2 (Nrf2)、血红素加氧酶-1 (HO-1)和醌氧化还原酶1 (NQO1)蛋白表达。结果与对照组相比,PD组大鼠跌落潜伏期显著缩短(P<0.05),脑组织中CAT活性、Nrf2、HO-1、NQO1蛋白表达水平显著降低(P<0.05),爬下时间显著延长(P<0.05),脑组织中MDA含量、IL-6、IL-1 β水平显著升高(P<0.05),脑组织出现病理改变;与PD组相比,神经妥乐平低、高剂量组大鼠跌落潜伏期显著延长(P<0.05),脑组织中CAT活性、Nrf2、HO-1、NQO1蛋白表达水平显著升高(P<0.05),爬下时间显著缩短(P<0.05),脑组织中MDA含量、IL-6、IL-1 β水平显著降低(P<0.05),脑组织病变减轻;与神经妥乐平高剂量组相比,通路抑制组大鼠跌落潜伏期显著缩短(P<0.05),脑组织中CAT活性、Nrf2、HO-1、NQO1蛋白表达水平显著降低(P <0.05),爬下时间显著延长(P <0.05),脑组织中MDA含量、IL-6、IL-1 β水平显著升高(P<0.05),脑组织病变程度加重。结论神经妥乐平可改善脑组织氧化应激、炎症损伤状态,提高PD大鼠行为功能,其机制可能与激活Nrf2/HO-1/NQO1通路有关。

Neurotropin exerts neuroprotective effects on Parkinson's disease rats through Nrf2/HO-1/NQO1 pathway

Objective To investigate the neuroprotective effect of neurotolepin on Parkinson’s disease(PD)rats and its related mechanisms.Methods SD rats were divided into control group,PD group(PD modeling),low-dose neurotropin group(PD modeling+intraperitoneal injection of 0.6 Nu·kg^-1neurotropin solution),high-dose neurotropin group(PD modeling+intraperitoneal injection of 1.2 Nu·kg^-1neurotropin solution) and pathway inhibitor group(PD modeling+intraperitoneal injection of 1.2 Nu·kg^-1neurotropin solution and 2 mg·kg^-1Nrf2 pathway inhibitor Brusatol).Rotating rod test and rod climbing test were used to test the behavioral function of rats and record the fall latency and the time to climb down;hematoxylin-eosin(He) staining was used to observe the pathological changes of brain tissue;the kit was used to detect catalase(CAT) activity,malondialdehyde(MDA) content and interleukin(IL)-6 and IL-1 β levels in brain tissue;Western blotting was performed to detect the protein expression of nuclear factor erythroid2-related factor 2(Nrf2),heme oxygenase-1(HO-1) and triphosphopyridine nucleotide quinine oxidoreductase 1(NQO1)in brain tissue.Results Compared with the control group,the fall latency of rats in the PD group was significantly shorter(P<0.05),the CAT activity,Nrf2,HO-1,and NQO1 protein expression levels in brain tissue were significantly reduced(P<0.05),the time to climb down was significantly prolonged(P<0.05),the MDA,IL-6 and IL-1 β levels in brain tissue were significantly increased(P<0.05),there were pathological changes in brain tissue;compared with the PD group,the fall latency of rats in the low-dose and high-dose neurotropin groups was significantly longer(P<0.05),the CAT activity,Nrf2,HO-1,and NQO1 protein expression levels in brain tissue were significantly increased(P<0.05),the time to climb down was significantly shorter(P<0.05),the MDA,IL-6 and IL-1 β levels in brain tissue were significantly reduced(P<0.05),the degree of brain tissue lesions was alleviated;compared with the high-dose neurotropin group,the fall latency of rats in the pathway inhibitor group was significantly shorter(P<0.05),the CAT activity,Nrf2,HO-1,and NQO1 protein expression levels in brain tissue were significantly reduced(P<0.05),the time to climb down was significantly prolonged(P<0.05),the MDA,IL-6 and IL-1 β levels in brain tissue were significantly increased(P<0.05),and the degree of brain tissue lesions was aggravated.Conclusion Neurotropin can improve the oxidative stress and inflammatory damage of brain tissue,and improve the behavioral function of PD rats,the mechanism may be related to the activation of Nrf2/HO-1/NQO1 pathway.