Hu Ming-jun, Liu Yong, Deng Cheng-guo, Chang Yan-qun, Wang Jia-ning, Dong Yong-zhang
Department of Histology and Embryology, Yunyang Medical College, Shiyan 442000, China.
Di Yi Jun Yi Da Xue Xue Bao. 2003 Jul;23(7):720-2.
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.
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.
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).
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.
探讨血管内皮生长因子165（VEGF165）基因治疗后，热休克蛋白70（HSP70）在脑梗死大鼠脑组织中的表达情况，从而为脑梗死的临床基因治疗提供分子依据。
将25只Wistar大鼠平均分为5组，即正常对照组、假手术对照组、大脑中动脉闭塞组（MACO组）、真核表达质粒组（pUCCAGGS组）和基因治疗组（接受pUCCAGGS/hVEGF165）。采用尼龙线结扎法建立永久性MACO大鼠模型，后两组分别将pUCCAGGS或pUCCAGGS/hVEGF165直接注入梗死区域。梗死后7天，处死大鼠获取脑组织，进行免疫组织化学检测HSP70表达。
正常对照组和假手术对照组大鼠脑皮质中HSP70表达水平相似且较低（P>0.05），而MACO组和pUCCAGGS组HSP70水平均显著升高（P<0.01），后两组间无差异（P>0.05）。基因治疗组HSP70表达最强（P<0.01）。在梗死灶周边区，MACO组、pUCCAGGS组和基因治疗组HSP70均高表达，前两组间相当（P>0.05），基因治疗组表达最高。在梗死区内观察到类似的表达模式（P<0.01）。
本研究观察到VEGF165基因治疗后大鼠HSP70表达升高，提示VEGF165基因具有诱导HSP70表达的能力。
