Heat shock protein 70 expression in the brain of rats with cerebral infarction after receiving vascular endothelial growth factor 165 gene therapy.

OBJECTIVE

To investigate the expression of heat shock protein 70 (HSP70) in the brain of rats with cerebral infarction after the administration of vascular endothelial growth factor 165 (VEGF165) gene therapy, thereby to provide molecular basis for clinical gene therapy of cerebral infarction.

METHODS

Twenty-five Wistar rats were divided equally into 5 groups, namely normal control group, sham-operated control group, middle cerebral artery occlusion group (MACO group), eukaryotic expression plasmid group (pUCCAGGS group) and gene therapy group (receiving pUCCAGGS/hVEGF165).Rat models of permanent MACO was established by ligation with nylon suture, and in the latter two groups, pUCCAGGS or pUCCAGGS/ hVEGF165 was directly injected into the infarcted area. Seven days after the infarction, the rats were killed to obtain the brain tissues for immunohistochemical detection of HSP70 expression.

RESULTS

In the rat brain cortex of the normal and sham-operated control group, similar low levels of HSP70 expression were detected (P >0.05), while in the MCAO group and pUCCAGGS group, HSP70 levels were both significantly higher (P <0.01), showing no differences between the latter two groups (P >0.05). Most intense HSP70 expression was detected in the gene therapy group (P <0.01). In the penumbra of the infarct area, MCAO, pUCCAGGS, and gene therapy group all had high expression levels of HSP70, which were comparable in the former two groups (P >0.05), with the highest expression levels occurring in the latter group. Within the infarct area, similar expression pattern was observed (P <0.01).

CONCLUSION

The elevated HSP70 expression in response to VEGF165 gene therapy in the rats as observed in this study suggests the potency of VEGF165 gene to induce HSP70 expression.