| Parkinson's disease (PD) is a progressive neurodegenerative disease causing motor deficits which have been mainly attributed to the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Consequently the focus of current PD therapy has been on the replacement of dopamine. Although DA replacement therapy can improve symptoms, long-term application will induce a lot of complications and side effects, which are difficult to control with currently available treatments. There is no one can reverse the progression of the disease in many anti- Parkinson's disease drugs, so neuron-protective treatment become research focus. As one of hematopoietic growth factors, erythropoietin is naturally produced by fetal liver and adult kidney, and it can stimulate erythropoiesis in the bone marrow in response to hypoxia. During the past decade, EPO has been used clinically in treating anemia inducing by chronic renal failure or cancer chemotherapy. Recently, many studies have demonstrated that EPO play a neuron-protective role in many central nervous system (CNS) disease, for example, EPO can reduce nerve cell damage induced by cerebral ischemia, trauma, status epilepticus. EPO has neuron-protection in many neurodegenerative diseases, such as Alzheimer disease, Huntington disease, amyotrophic lateral sclerosis, Parkinson's disease and so on. In addition, with advancing age, EPO levels gradually reduced in CNS, suggesting that EPO may be related to aging-related neurodegenerative disease. EPO has recently been demonstrated to provide neuron-protection in a variety of neurons including nigral DA neurons against experimental insults. However, the mechanisms of neuron-protection are largely unknown. It has been confirmed that EPO protected DA neurons by inhibiting apoptosis, inhibiting the release of glutamate and suppressing oxidative stress. Recently it was suggested that EPO could inhibit the production of inflammatory cytokine, play an anti-inflammatory role to protect DA neurons, however, this conclusion has caused controversy.In the present study, we examined the influence of rhEPO on microglia and glial cell line-deriver expression, whether rhEPO elicited its neuroprotection via an anti-inflammatory mechanism.ObjectiveTo study the effects of recombinant human erythropoietin (rhEPO) on microglia and inflammatory factors in a rat model of Parkinson's disease induced by 6-hydroxydopamine(6-OHDA).MethodsSD rats were randomly divided into four groups:A group(rhEPO+6-OHDA),B group(saline+6-OHDA,C group(6-OHDA),D group(saline). (1) A group:On 24 hours after right striatum stereotactic rejection of rhEPO, ipsilateral substantia nigra (SN) stereotactic rejection of 6-OHDA; (2) B group:On 24 hours after right striatum stereotactic rejection of saline(equal quantity of rhEPO), ipsilateral substantia nigra (SN) stereotactic rejection of 6-OHDA; (3) C group:right substantia nigra (SN) stereotactic rejection of 6-OHDA; (4) D group:right substantia nigra (SN) stereotactic rejection of saline(equal quantity of 6-OHDA).4 weeks after the operation, ten rats which were all successful model of Parkinson's disease (PD) were selected in A, B, C group and ten rats were selected in D group to examine indicators:the numbers of tyrosine hydroxylase (TH) positive neurons and CD11b positive cells in the substantia nigra (SN) were observed by immunohistochemistry; the quantity of tumor necrosis factor-a(TNF-a) and inducible nitric oxide synthase (iNOS) in blood serum were examined by enzyme linked immuno sorbent assay (Elisa); the expression of TNF-a and iNOS mRNA in substantia nigra (SN) were evaluated by reverse transcription polymerase chain reaction(RT-PCR).ResultsCompared with D group, the number of TH+ neuros of SN reduced greatly in A group(P<0.05), the number of CD11b+ cells in SN increased markedly in A group(P <0.05), the content of iNOS and TNF-a in blood serum increased greatly in A group(P<0.05), the expression of iNOS mRNA and TNF-a mRNA in SN increased markedly in A group(P<0.05); compared with B and C group, the number of TH+ neuros in SN increased remarkably in A group(P<0.05), the number of CD11b+ cells in SN decreased markedly in A group(P<0.05), the content of iNOS and TNF-a in blood serum decreased greatly in A group(P<0.05), the expression of iNOS mRNA and TNF-a mRNA in SN decreased markedly in A group(P<0.05).ConclusionProbably because of blocking activation of microglia and the expression of iNOS and TNF-α, rhEPO could prevent the impairment of DA neurons induced by 6-OHDA and protect DA neurons. |
PDF Full Text Request