NEUROPROTECTIVE EFFECTS OF RECOMBINANT ADENO-ASSOCIATED VIRUS EXPRESSING VASCULAR ENDOTHELIAL GROWTH FACTOR ON RAT TRAUMATIC SPINAL CORD INJURY AND ITS MECHANISM

Objective To investigate the neuroprotective effects of recombinant adeno-associated virus(rAAV) expressing vascular endothelial growth factor(VEGF) on traumatic spinal cord injury(SCI) of rat and its mechanisms.Methods The 144 male Sprague Dawley rats were randomly divided into 4 groups,and each group contained 36 rats.The rats in sham group(group A) received dorsal laminectomy without SCI and microinjection,the rats in model control group(group B),rAAV-green fluorescent protein(GFP) group(group C),and rAAV-hVEGF165-GFP group(group D) received dorsal laminectomy with SCI and injection of 20 μL saline,rAAV-GFP viruses,or rAAV-hVEGF165-GFP viruses,respectively.At 3 and 7 days after operation,Basso-Beattie-Bresnahan(BBB) score was used to evaluate the neurologic function.At 7 days after operation,Nissl’s body staining was used to evaluate the histopathological changes;apoptosis was con rmed by transmission electron microscope examination and TUNEL staining;the expression of aquaporin 4(AQP-4) was detected by Western blot assay.At 1,3,5,and 7 days,ELISA assay was used to detect the VEGF165protein expression.Results According to BBB scores,the neurologic function in group D was signi cantly better than those in groups B and C at 3 and 7 days after operation(P 0.05).Nissl’s body staining showed that tissue damage in group D was signi cantly milder than those in groups B and C at 7 days after operation(P 0.05).ELISA results showed that VEGF165protein expression was slowly-released in low dose in group D,and the expression in group D was signi cantly higher than that in groups A,B,and C at 3,5,and 7 days after operation(P 0.05).The results of transmission electron microscope and TUNEL staining showed that apoptosis rate of spinal cord neurons in group D was signi cantly lower than that in groups B and C at 7 days after operation(P 0.05).The results of Western blot showed that AQP-4 expression in group D was signi cantly decreased when compared with that in groups B and C at 7 days after operation(P 0.05).Conclusion The rAAV expressing VEGF has neuroprotective e ects by inhibiting apoptosis of spinal cord neurons and relieving spinal cord edema.