首页> 外文期刊>World Journal of Gastroenterology >Hepatocyte growth factor gene therapy prevents radiation-induced liver damage.
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Hepatocyte growth factor gene therapy prevents radiation-induced liver damage.

机译:肝细胞生长因子基因疗法可防止辐射引起的肝损伤。

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摘要

AIM: To transfer human HGF gene into the liver of rats by direct electroporation as a means to prevent radiation-induced liver damage. METHODS: Rat whole liver irradiation model was accomplished by intra-operative approach. HGF plasmid was injected into liver and transferred by electroporation using a pulse generator. Control rats (n = 8) received electrogene therapy (EGT) vehicle plasmid and another 8 rats received HGF-EGT 100 mug 48 h before WLIR. Expression of HGF in liver was examined by RT-PCR and ELISA methods. Apoptosis was determined by TUNEL assay. Histopathology was evaluated 10 wk after whole liver irradiation. RESULTS: Marked decrease of apoptotic cells and down-regulation of transforming growth factor-beta 1 (TGF-beta1) mRNA were observed in the HGF-EGT group 2 d after liver irradiation compared to control animals. Less evidence of radiation-induced liver damage was observed morphologically in liver specimen 10 wk after liver irradiation and longer median survival time was observed from HGF-EGT group (14 wk) compared to control rats (5 wk). (P = 0.031). CONCLUSION: For the first time it has been demonstrated that HGF-EGT would prevent liver from radiation-induced liver damage by preventing apoptosis and down-regulation of TGF-beta1.
机译:目的:通过直接电穿孔将人HGF基因转移到大鼠肝脏中,以防止辐射引起的肝损伤。方法:采用术中方法建立大鼠全肝照射模型。将HGF质粒注射入肝脏,并使用脉冲发生器通过电穿孔转移。对照组(n = 8)接受电基因治疗(EGT)载体质粒,另外8只大鼠在WLIR前48 h接受HGF-EGT 100杯。通过RT-PCR和ELISA方法检查肝中HGF的表达。通过TUNEL测定法确定细胞凋亡。全肝照射后10周评估组织病理学。结果:与对照动物相比,HGF-EGT组在肝照射后2 d凋亡细胞明显减少,转化生长因子β1(TGF-beta1)mRNA的表达下调。与对照组大鼠(5 wk)相比,在肝照射后10 wk的肝脏标本中,从形态学上观察不到辐射诱发的肝损伤的证据,HGF​​-EGT组(14 wk)观察到更长的中位生存时间。 (P = 0.031)。结论首次证明,HGF-EGT可通过防止细胞凋亡和TGF-beta1的下调来防止肝脏受到辐射诱导的肝损伤。

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