Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh 160014, India.
Brain Res. 2012 Aug 30;1471:13-22. doi: 10.1016/j.brainres.2012.06.050. Epub 2012 Jul 10.
Neuro-inflammation and oxidative stress plays a key role in the pathophysiology of Parkinson's disease (PD). Studies demonstrated that neuro-inflammation and associated infiltration of inflammatory cells into central nervous system are inhibited by 3-hydroxy-3-methyl glutaryl co-enzyme A (HMG-CoA) reductase inhibitors. Based on these experimental evidences, the present study has been designed to evaluate the neuroprotective effect of HMG-CoA reductase inhibitors (atorvastatin and simvastatin) against 6-hydroxydopamine (6-OHDA) induced unilateral lesion model of PD. In the present study, the animals were divided into nine groups (n=15 per group). Group I: Naive (without treatment); Group II: Sham (surgery performed, vehicle administered); Group III: Atorvastatin (20mg/kg); Group IV: Simvastatin (30 mg/kg); Group V: Control [Intrastriatal 6-OHDA (20 μg; single unilateral injection)]; Groups VI and VII: 6-OHDA (20 μg)+atorvastatin (10mg/kg and 20mg/kg) respectively; Groups VIII and IX: 6-OHDA (20 μg)+simvastatin (15 mg/kg and 30 mg/kg) respectively. Intrastriatal administration of 6-OHDA (20 μg; 4 μl of 5 μg/μl) significantly caused impairment in body weight, locomotor activity, rota-rod performance, oxidative defense and mitochondrial enzyme complex activity, and increase in the inflammatory cytokine levels (TNF-α and IL-6) as compared to naive animals. Atorvastatin (20mg/kg) and simvastatin (30 mg/kg) drug treatment significantly improved these behavioral and biochemical alterations restored mitochondrial enzyme complex activities and attenuated neuroinflammatory markers in 6-OHDA (20 μg) treated animals as compared to control group. The findings of the present study demonstrate the neuroprotective potential of statins in experimental model of 6-OHDA induced Parkinson like symptoms.
神经炎症和氧化应激在帕金森病（PD）的病理生理学中起着关键作用。研究表明，3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂可抑制神经炎症和相关炎症细胞浸润中枢神经系统。基于这些实验证据，本研究旨在评估 HMG-CoA 还原酶抑制剂（阿托伐他汀和辛伐他汀）对 6-羟多巴胺（6-OHDA）诱导的单侧 PD 模型的神经保护作用。在本研究中，将动物分为 9 组（每组 15 只）。组 I：未处理的对照（未治疗）；组 II：假手术（手术但未给药）；组 III：阿托伐他汀（20mg/kg）；组 IV：辛伐他汀（30mg/kg）；组 V：对照组[纹状体注射 6-OHDA（20μg；单次单侧注射）]；组 VI 和 VII：6-OHDA（20μg）+阿托伐他汀（10mg/kg 和 20mg/kg）；组 VIII 和 IX：6-OHDA（20μg）+辛伐他汀（15mg/kg 和 30mg/kg）。纹状体注射 6-OHDA（20μg；4μl 的 5μg/μl）显著导致体重、运动活性、旋转棒性能、氧化防御和线粒体酶复合体活性受损，以及促炎细胞因子水平（TNF-α和 IL-6）升高与未处理的动物相比。阿托伐他汀（20mg/kg）和辛伐他汀（30mg/kg）药物治疗显著改善了这些行为和生化改变，恢复了线粒体酶复合体活性，并减轻了 6-OHDA（20μg）处理动物的神经炎症标志物，与对照组相比。本研究的结果表明，他汀类药物在 6-OHDA 诱导的帕金森样症状的实验模型中具有神经保护潜力。
