VEGF-165基因对创伤性脑损伤脑血流动力学影响的实验研究

Dynamic change of cerebral hemodynamic after traumatic brain injury in rats following VEGF-165 gene therapy

目的研究外源性血管内皮细胞生长因子(VEGF)基因治疗大鼠创伤性脑损伤(TBI)后脑灌注的变化,了解其血流动力学改变。方法创伤性脑损伤大鼠模型建立后随机分为3组:治疗组,质粒对照组,外伤组。通过RT-PCR检测脑伤后1 h、6 h、24 h、3 d、7 d、14 d VEGF mRNA在损伤局部的表达改变;应用CT灌注像(CTP)研究不同时间脑血流量(CBF)、脑血容量(CBV)等参数在VEGF-165基因治疗前后的动态变化。结果 VEGF-165基因治疗创伤性脑损伤大鼠后经RT-PCR扩增的VEGF mRNA绝对积分光密度值水平显著高于外伤组和质粒对照组(P<0.05)。CTP参数和伪彩图均显示基因治疗组脑灌注在伤后24 h CBF、CBV有增高趋势,伤后3 d、7 d脑灌注明显高于TBI组(P<0.05),虽然伤后14 d CBF、CBV开始降低,但和TBI组比较仍然较高。结论本研究结果显示大鼠创伤性脑损伤后外源性VEGF基因能够提高脑损伤组织的脑灌注,改善脑损伤部位微循环,为损伤组织的恢复提供基础。

Objective To study the exogenous vascular endothelial growth factor （VEGF） gene therapy for traumatic brain injury （TBI） in rats by using CT perfusion （CTP） and to probe into the dynamic changes in local cerebral hemodynamic. Methods TBI rat models were established and were randomly divided into 3 groups, that is, TBI ＋ VEGF group, control group, and TBI group. The expressions of VEGF mRNA in injury area were detected by reverse transcription polymerase chain reaction （RT-PCR） at 1 h, 6 h, 24 h, 3 d, 7 d, 14 d after brain injury. CT perfusion （CTP） at different time points was used to monitor the dynamic changes of the cerebral blood flow （CBV）, cerebral blood volume （CBF） and other parameters before and after VEGF-165 gene therapy. Results Integral optical density （IOD） levels in TBI ＋ VEGF group were significant higher than that of TBI and vector control group （P 〈0. 05）. CTP parameters and false-color image showed that CBF and CBV was increasing in TBI ＋ VEGF group at 24 h after injury, and at 3 d and 7d after injury the cerebral perfusion was significantly higher in TBI ＋ VEGF group than in TBI group （P 〈 O. 05）. At 14 d after injury, CBF and CBV began to decrease, but they were still higher than that of TBI group. Conclusion Exogenous VEGF gene can increase the cerebral perfusion after the traumatic brain injury and improve the microcirculation which provides the basis for the recovery of brain tissues.