[Protective effect of exogenous superoxide dismutase against rat midbrain dopaminergic neuron apoptosis induced by 6-hydroxydopamine].
OBJECTIVE
To observe the changes of total antioxidant ability of rat midbrain and T-superoxide dismutase (T-SOD) activity, and define the relation between oxidative stress and dopaminergic neuron apoptosis induced by 6-hydroxydopamine (6-OHDA), observing also the protection of the exogenous SOD against the neuron apoptosis.


METHODS
A total of 144 SD rats was randomized into normal control, model control, model, treatment control and treatment groups according to different treatments the rats received. The treatment group was subdivided into A, B, C, D and E groups with different treating times after model establishment. The midbrain total antioxidant ability, T-SOD activity, and active oxygen were measured by using corresponding detection kits, and the behavioral changes and the changes of tyrosine hydroxylase(TH) immunoreactivity and apoptotic cells in the substantia nigra compact part (SNcp) were assessed and measured in each group.


RESULTS
After injection of 6-OHDA in SNcp of rats, the total antioxidant ability did not undergo obvious changes. Active oxygen in the midbrain increased remarkably to 130+/-17 U/mg prot and T-SOD activity was reduced. Injection of exogenous SOD caused the rotational speed of the rats to decrease from 166.7+/-31.0 to 87.6+/-25.0 circle/30 min following intraperitoneal injection of apomorphine (0.5 mg/kg b.w.), with obviously decreased active oxygen (P<0.05) and enhanced T-SOD activity. TH immunoreactivity and cell apoptosis in the SNcp presented corresponding changes. In the treatment groups, different time schedules for exogenous SOD injection into the SNcp produced different effects accordingly.


CONCLUSIONS
Oxidative stress plays an important role in doparminergic neuron apoptosis induced by 6-OHDA injection. Exogenous SOD in the SNcp effectively reduces active oxygen, promotes the antineurotoxic ability of doparminergic neurons, reduces doparminergic neuron apoptosis and ameliorated the rat rotating behavior. Exogenous SOD has short-term antioxidant effect, which weakens progressively over extended time.
Xu
Qiang
Q
Department of Neurosurgery, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China.
Xu
Ru-xiang
RX
Zhang
Shi-zhong
SZ
Zhang
Wang-ming
WM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D019610:Cytoprotection; D006892:Hydroxydopamines; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012399:Rotation; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D006892:Hydroxydopamines; D017382:Reactive Oxygen Species; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase