Mechanism Of Alpha Lipoic Acid Intervening On Iron Deposition In The Substantia Nigra Of Parkinson’s Disease Model Rat

Objective: To explore the molecular mechanism of α-lipoic acid(LA)scavenging the midbrain SN iron accumulation, through observing the expressions of divalent metal transport 1(DMT1), Ferroportin 1(FP1), and Ferritin in the midbrain SN of the model rats with 6-OHDA induced Parkinson’s disease.Methods: 130 male SD rats were randomly divided into 5 groups: Control Group of 30 rats(with intracranial injection of saline solution), then 20 rats out of the Control Group were selected randomly as Sham operated Group after four weeks; Model Group of 100 rats(with intracranial injection of 6-OHDA), four weeks later 80 rats out of Model Group were randomly divided into 4 groups:the PD Model Group(20 rats, injection of nothing) and Low Agent Group(20 rats, injection of LA), Medium Agent Group(20 rats, injection of LA), and High Agent Group(20 rats, injection of LA). Unilateral intrastriatal 6-OHDA injection(right side) was performed on anesthetized rats using stereotaxic apparatus. Control Group received a single injection of 0.9% saline. Low Agent Group received a single injection of 25mg/kg/d of LA, Medium Agent Group was injected 50mg/kg/d of LA, and High Agent Groups was injected 100mg/kg/d of LA for 14 consecutive days. After the treatment, the right midbrain SN of the rats in all groups were taken for the examination to the expression levels of DMT1, FPl, and Ferritin by Western-Blot. The number of the iron positive cells within SN were counted by the Prussian blue iron stain method. In addition, the iron contents of SN was performed using the atomic absorption spectrophotometer.Results:(1) Compared to the Sham operated Group, the expression levels of DMT1 within SN in the PD Model Group, Low Agent Group, Medium Agent Group, and High Agent Group were all significantly increased(P<0.05), while the expression levels of FP1 and Ferritin were both reduced(P<0.05); The content of iron and the amount of the iron positive cells in SN of the PD ModelGroup, of Low Agent Group, of Medium Agent Group, of High Agent Groupwere all significantly increased(P < 0.05).(2) Compared to the PD Model Group, the expression levels of DMT1 within SN in the Low Agent Group, Medium Agent Group, and High Agent Group were all significantly reduced(P<0.05),but the expressions of FP1 were all significantly raised(P<0.05), the expressions of Ferritin in the Medium Agent Group and High Agent Group were significantly upgraded(P<0.05), while the expressions of Ferritin was no statistical differences on in the Low Agent Group(P>0.05). The content of iron and the number of iron cells in SN of the Low Agent Group, Medium Agent Group, and High Agent Group were all significantly reduced(P < 0.05).(3) Compared to the Low Agent Group, the expressions of FP1 and Ferritin of SN in the Medium Agent Group, and High Agent Group were both significantly raised(P<0.05), while the expressions of DMT1 had been significantly reduced. The contents of iron and the numbers of iron positive cells in SN in the Medium Agent Group, and High Agent Group were significantly reduced compared with Low Agent Group(P<0.05).(4) Compared between the Medium Agent Group and High Agent Group, the FP1 and Ferritin in SN of the High Agent Group were significantly raised(P<0.05), the number of the iron positive cells in SN of the High Agent Group was significantly reduced(P<0.05), but there were no statistical differences in the expression levels of DMT1 or the content of iron in SN of the High Agent Group(P>0.05).Conclusion:(1) LA could scaveng the midbrain SN iron accumulation by 6-OHDA induced Parkinson’s disease model rats.(2) The molecular mechanism of LA scavenging the midbrain SN iron accumulation are through the down-regulation expressions of DMT1, and the up-regulation expressions of Ferroportin 1(FP1), and Ferritin to suppress the oxidative stress response and maintain the stable status of iron balance.