肝细胞生长因子基因治疗促进乙酸性胃溃疡组织再生修复的效果  

Regenerative repair effect of hepatocyte growth factor gene on gastric ulcer in rats

作　　者：哈小琴[1,2] 郭文家 张萍[1] 杨淑娟[1] 陆润兰[1] 李兵 赵勇[1] 杨志华[1] 白燕青[1] 

机构地区：[1]兰州军区兰州总医院检验医学中心,甘肃兰州730050 [2]甘肃省干细胞与基因药物重点实验室,甘肃兰州730050

出　　处：《中国生物制品学杂志》2017年第10期1046-1049,共4页Chinese Journal of Biologicals

基　　金：全国十二五面上项目(CWS11C229);甘肃省卫生厅项目(GSWST09-17)

摘　　要：目的评价肝细胞生长因子(hepatocyte growth factor,HGF)基因治疗促进大鼠乙酸性胃溃疡创面组织再生修复的效果。方法 Wistar大鼠乙酸注射诱导建立大鼠胃溃疡模型,建模后第5天,将模型大鼠随机分为3组:TPH(携带HGF基因真核表达质粒的减毒沙门菌)治疗组、TP(携带空真核表达质粒的减毒沙门菌)治疗组和模型对照组,分别给予含1×10~9 cfu TPH、1×10~9 cfu TP的10%NaHCO_3溶液及等体积(1 ml)10%NaHCO_3溶液灌胃,1次/3 d,共3次。末次灌胃治疗后第21天,取病变部位胃组织,肉眼观察溃疡创面愈合大小,显微镜下观察各组胃溃疡创面组织再生修复情况,ELISA法检测不同时间点(末次灌胃后第1、3、7、14、21天)HGF在溃疡局部组织中的表达水平。结果 TPH治疗组大鼠溃疡创面小而浅,基底细胞增生明显,胃黏膜上皮增生移行显著,且基底组织中多见毛细血管;而TP治疗组和模型对照组溃疡创面基底细胞增生及黏膜上皮增生移行均不明显;灌胃治疗后不同时间点TPH治疗组胃黏膜组织中HGF蛋白的表达水平均明显高于TP治疗组和模型对照组(P<0.05或<0.01),且呈时间依赖性。结论 HGF基因治疗可促进乙酸性大鼠胃溃疡创面的组织再生修复,加快溃疡愈合。Objective To evaluate the promoting effect of hepatocyte growth factor（HGF） gene therapy on tissue regeneration in rats with gastric ulcer induced by acetic acid. Methods Gastric ulcer model was established by subserosal injection with acetic acid in Wistar rats. The model rats were randomly divided into three groups on day 5 after establishment, and treated with 10% sodium hydrogen carbonate solution containing 1 × 10^9 cfu TPH（attenuated salmonella carrying eukaryotic expression vector for HGF gene）, 10% sodium hydrogen carbonate solution containing 1 ×10^9cfu TP（attenuated salmonella carrying empty eukaryotic expression vector） and 10% sodium hydrogen carbonate solution（control）at an equal volume（1 ml）by lavage respectively, once 3 d for 3 times. The stomach tissues of rats were collected on day 21 after the last lavage, observed for ulcer healing visually, and for regenerative repair by microscopy.The HGF expression levels in ulcer tissue on days 1, 3, 7, 14 and 21 after the last lavage were determined by ELISA.Results The wound surface of ulcer of rats in TPH group was small in area and shallow, while the basal cells were proliferated significantly, the gastric mucosa epithelial cells were proliferated and migrated significantly, and capillary vessels were observed in basal tissue. However, no obvious proliferation of basal cells or proliferation and migration of gastric mucosa epithelial cells were observed in TP and control groups. The expression levels of HGF at various time points after lavage in TPH group were significantly higher than those in TP and control groups（P〈0. 05 or P〈0. 01）.Conclusion HGF gene therapy accelerated the healing of gastric ulcers via stimulating the proliferation of gastric epithelial cells and basal cells of gastric ulcer wound.

关 键 词：肝细胞生长因子 基因治疗 组织再生 胃溃疡 大鼠 

分 类 号：R364.33[医药卫生—病理学] R458.9[医药卫生—基础医学]