| Objective: Parkinson′s disease is a progressive neurodegenerative disorder, commonly in middle-aged and elderly people, of which the incidence is increased with the aging population. There are no effective ways to cure PD because of the causes and exact mechanism have not yet been fully explained. At the present time, the methods, like dopamine replacement treatment, used in the clinical work are mainly aimed at the symptoms of PD, which failed to halt the degenerative process. In addition, the severe side effects occurred and the pharmacodynamics declined with long-term use of dopamine neuron drugs, which cause great spiritual and economic burden to their families and patients'low quality of life. Thus, people are look forward to developing new medicines to treat PD. In recent years, neurological inflammation with characteristic of microglia's activity is attached great importance in the mechanism of PD. Microglia, the immune cells in the brain, play a role of immunological surveillance under normal condition. However, microglia is easily activated in response to injuries and release all kinds of neurological toxic cellular factors, including tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), arachidonic acid metabolite, nitric oxide (NO), and reactive oxygen radical (ROR), etc, which lead to the death of dopaminergic neuron. So, the degeneration of dopaminergic neuron and the progression of PD can be prevented partially by inhibiting inflammatory reaction of Microglia, or reducing the neurological toxic cellular factors released by Microglia, That is the reason why the research of antiinflammatory agent to treat PD have being hotspot. We have built a inflammation-mediated model of PD by the intranigral injection of LPS in this study, and interfered experimental animals by anti-inflammatory medicine including Chinese medicine, resveratrol, and minocycline. Moreover, using the technologies of immunohistochemistry, western blot, we observed the two medicine's protective effects to the injured dopaminergic neuron by LPS and the influences to Microglia's activity and the expression of NF-kB. This study is aim to observe resveratrol and minocycline's protective effects to dopaminergic neuron, and investigate the protective mechanism of the two medcines, which make a basis for developing the new medcines to treat PD. As so far, there are rare relative reports.Methods: Fourty-eight male Sprague-Dawley rats were randomly divided into four groups: PBS group, PD group, Resveratrol treated group, Minocycline treated group. The rat model of PD is made by injecting LPS into SNs. Resveratrol (20mg/kg/d) or Minocycline (50mg/kg/d) was administrated to gastro, 3 hours before the injection of LPS till 14th days. At the end of survival time after injection of LPS in the SNs of rats , every rat was watched whether or not there are behaviours of PD from means of action by apomorphine intraperitoneal injection, the number of tyrosine hydroxylase(TH) positive neurons and NF-κB positive neurons and the morphological changes of OX-42 positive microglias in the SNs of rats were assayed by immunohistochemistry; TH and NF-κB protein expression by immunoblotting.Results: The rats of every experimental group can be induced rotational behavior by injecting LPS, but the control group hasn't any rotational behavior. The mean rotational rounds of PD group within 30 min are 196.90±9.52. The mean rotational rounds of MC and Res groups, 120.03±10.50, 106.57±7.89 respectivly, are significantly lessen than control group (P<0.01).Different number of TH positive neuron are found in all groups. The number of TH positive cells and the expression of TH protein in substantial nigra of PD group was significantly decreased(P<0.01), compared with control group. There are more TH positive neurological cells in Res group, which has significant difference(P<0.05), compared with MC group. Most OX-42 positive Microglia show kladodromous, smaller cellular body, slim synapse. Small pat of OX-42 positive Microglia show short synapse. Activated Microglia in MC and Res groups are decreased significantly, compared with PD group. Less NK-kB positive cells are observed in control group. More NF-κB positive cells was observed in PD group compared with PD group(P<0.01). NF-κB positive cells are less in Res and MC groups than PD group(P<0.01). NF-κB positive cells in Res group are even less than that in MC(P<0.05). The outcome of Western blot indicate that substantial expression of TH protein and micro expression of NF-κB protein in SNs within control group. The contrary outcome was observed in PD group. The expression of TH protein is increased in MC and Res groups and that of NF-κB P65 is decreased compared with PD(P<0.01). The expression of TH protein is increased and that of NF-κB P65 is decreased in Res group, which have significant difference, compared with MC group(P<0.05).Conclusion: LPS can induce the activity of Microglia cells in SNs of SD rat, increase the expression of NF-κB protein and decrease the number of TH positive cells and the expression of TH protein. Resveratrol and Minocycline can inhibit the activity of Microglia cells and the expression of NF-KB. The two medcines can also protect dopaminergic neuron, which may be effective medicine to treat PD.
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