抄録
The renin angiotensin system (RAS) has emerged as an important partaker in the etiology of Parkinson's disease (PD), extending beyond its cardio-reno effects. The current study investigated the possible therapeutic effect of angiotensin (Ang) 1-7, a MAS receptor (MASR) agonist and a counter-regulatory peptide of RAS, on modulating Ang1-7/MASR and HMGB-1/RAGE axis in 6-hydroxydopamine (OHDA)-lesions PD model. Male Wistar rats were allocated into 6 groups (n=8): (1) sham-operated (SO), (2) SO+Ang1-7, (3) 6-OHDA unilateral intrastriatal injection to induce PD, (4) 6-OHDA+Ang1-7, (5) 6-OHDA+A-779, a MASR antagonist and (6) 6-OHDA+A-779+Ang1-7. Treatments were instilled intrastriatally for 7 consecutive days after establishment of valid PD by apomorphine test. Ang1-7 decreased apomorphine-induced contralateral turns and improved motor performance and muscle coordination. Moreover, Ang1-7 preserved dopaminergic neurons in substantia nigra noted by the increased tyrosine hydroxylase immunoreactivity. Additionally, Ang1-7 downregulated AT-1R, HMGB-1, and RAGE expression along with an increase in ρY705-STAT-3 and SOCS3. Furthermore, Ang1-7 reduced the increment in p38 (ρT180/Y182)-MAPK, p65-NF-κB, TNF-α, NADPH oxidase, TBARS and PARP-1. Conversely, the effect of Ang1-7 was partially reversed by coadminstration with A779. Our results suggest that Ang1-7 plays an important therapeutic role against neurotoxicity and motor impairment associated with PD by the suppression of HMGB-1/RAGE downstream oxidative-inflammatory events and the modulation of AT-1R mediated by Ang1-7/MASR cue
