The Effects Of Ginkgolides On D-glu Contents In Midbrain Of Parkinsonina Mice

Objective To study the protection effect of ginkgolides on Parkinsonian mice and to explore the mechanism; To observe the change of D-glutamate(D-Glu) content in midbrain of Parkinsonina mice and the effect of ginkgolides on it. To explore the toxicity of the D-Glu on glutamatergic neurons and its correlation to the progress of Parkinson's disease(PD).Methods 120 health adult C57-BL/6 male mice (body weight 20~22g) were randomly divided into 3 groups, 40 mice in each group. The mice in the PD model group (PDG) were treated with MPTP (30mg/kg, dissolved in saline, intraperitoneal injection) for 7 days and were treated with 0.8%CMC (18mg/kg) 8 hours before injection; ginkgolides group(GinG) were treated with MPTP (30mg/kg) for 7 days and were treated with ginkgolides (18mg/kg,dissolved in 0.8%CMC, intragastric administration) 8 hours befor injection; control group (ConG) were treated with 0.8%CMC and saline as much as the GinG and lasted 7 days. 10 mice in each group were chosen on the next day of 1,3,5 and 7 days after drugs administration. The glutamatergic neurons in the substantia nigra and striatum corpora were observed by using immunofluorescence histochemical method. The change of D-Glu content in midbrain was detected by using reversed highperformance liquid chromatography method.Results A large number of glutamatergic neurons could be seen in ConG which are small to medium-sized oval neurons in the substantia nigra and striatum corpora; compared with ConG, the glutamatergic neurons in substantia nigra and striatum of PDG had little change in the volume and shape after 1d MPTP injection, 3d later the number reduced (P<0.01) and the reduction was more obviouse after 7d, the staining significantly smeared out obviousely; compared with PDG, the number of glutamatergic neurons of GinG had little change after 1d, and significantly increased 3d later(P<0.01), then was always lower than PDG, but had no significant difference compared with ConG. D-Glu content of PDG in midbrain significantly increased compared to ConG after 1d of MPTP injection (P <0.01) and gradually reduced 3d later. It had a further reduction 5d and 7d later, but was still higher than the ConG(P<0.05); D-Glu content in GinG decreased significantly compared with PDG after 1d (P <0.01), then was always lower than PDG and was reduced to a minimum after 5d, 7d later the number rebounded a little, but showed no significant difference compared with ConG.Conclusions 1. Ginkgolides could antagonize the excitotoxicity induced by glutamate and have some protective effect on the glutamatergic neurons. 2. D-Glu may be involved in the pathogenesis of PD and has the same excitotoxicity as L-Glu in the genesis and development of PD. 3. Ginkgolides is expected to become an effective preventive treatment adjuvant drug for PD.