帕金森病,神经干细胞,GDNF z-bo 2020-09-22 287

　　OBJECTIVE: To investigate the therapeutic effect of neural stem cells (mNSCs) derived from the midbrain of fetal rats at 14-15 days of pregnancy, modified by glial-derived neurotrophic factor (GDNF) gene and transplanted into the striatum of Parkinson's disease model rats.

　　Method: Take fetal mice 14-15 days after pregnancy to separate the midbrain ventral tissue under a dissecting microscope for mNSCs culture, culture for 5 days and then perform GFP/GDNF gene modification. The establishment of the PD rat model refers to the stereotactic map of the rat brain, and 6-hydroxydopamine is injected into the ventral region of the midbrain dorsal cover and the medial forebrain tract. PD rats were randomly divided into groups, genetically modified stem cells and non-gene modified stem cells were transplanted into the striatum of Parkinson's disease rats, and a blank mNSCs (PBS replacement) transplantation group, GFP gene modified mNSCs transplantation group, and GDNF gene modified mNSCs were established Three experimental groups in the transplantation group. Behavioral evaluation was performed before and after cell transplantation. The number of rotations induced by intraperitoneal injection of apomorphine (APO 0.5 mg/kg) in PD rats was used as a therapeutic evaluation method for cell transplantation. Immunofluorescence histochemistry identified the survival, migration and differentiation of transplanted cells.

　　Results: Compared with the control group and the GFP gene modified neural stem cell transplantation group, the GDNF gene modified neural stem cell transplantation group showed significant improvement in behavior; 56 days after transplantation, the GDNF gene modified mNSCs transplantation group detected more cell survival than the other two groups. The differentiation of functional neurons has an increasing trend compared with the other two groups.

　　Conclusion: GDNF gene-modified mNSCs transplantation can significantly improve the dyskinesia of PD rats, and its molecular mechanism needs to be further studied.