肝细胞生长因子基因治疗促进大鼠放创复合伤愈合  

Gene therapy with hepatocyte growth factor promotes the healing of combined radiation-trauma injury in rats

作　　者：卢育新 马琼 崔玉芳 程晓晨 肖凤君 张庆林[1] 杜丽 LU Yu-xin;MA Qiong;CUI Yu-fang;CHENG Xiao-chen;XIAO Feng-jun;ZHANG Qing-lin;DU Li(Institute of Radiation Medicine,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]军事科学院军事医学研究院辐射医学研究所,北京100850

出　　处：《军事医学》2023年第2期111-115,共5页Military Medical Sciences

基　　金：后勤科研重大项目(ALJ19J002)。

摘　　要：目的 应用携带肝细胞生长因子(HGF)基因的质粒(pHGF)对大鼠放创复合伤进行基因治疗,探究其促愈作用。方法 120只SPF级雌性Wistar大鼠按体重随机分为单伤组、伤照组、伤照+阳性药(重组人表皮生长因子外用溶液,金因肽)治疗组(JYT组)和伤照+pHGF治疗组(HGF组),每组30只。大鼠经致伤和照射后建立放创复合伤模型,建模后即刻HGF组在创面一次性给予pHGF质粒,JYT组给予金因肽治疗,伤照组给予等体积的PBS。伤照后3、7、14、21、28和35 d描记伤口面积、检测外周血象和伤口组织羟脯氨酸含量,并进行病理检测和伤口肉芽组织毛细血管计数,研究pHGF对大鼠放创复合伤的促愈作用。结果 伤照后3、28及35 d,大鼠体重及外周血白细胞计数显著降低。伤照后11 d内,HGF组伤口相对面积小于或显著小于伤照组(P<0.05)。伤照后7、14 d,HGF组羟脯氨酸含量明显高于JYT组(P<0.05)。毛细血管密度结果显示,伤照后3、7 d,HGF组肉芽组织毛细血管密度明显大于伤照组和JYT组(P<0.05);伤照后14 d,HGF组毛细血管密度小于伤照组(P<0.05)。病理检测结果显示,HGF组大鼠创面肉芽组织出现较早,成纤维细胞增生活跃,肉芽组织和新生毛细血管均较伤照组丰富,且愈合后期创面角质层生成和再上皮化过程明显较伤照组快。结论 pHGF能有效促进伤口区胶原和毛细血管形成、伤口区肉芽组织生成,以及角质形成细胞增殖,可明显促进大鼠放创复合伤的早期愈合。Objective To explore the healing effect of gene therapy with the plasmid hepatocyte growth factor(pHGF) carrying HGF gene against compound injury in rats. Methods One hundred and twenty SPF Wistar rats were randomly divided into the single injury group,combined radiation-trauma injury group,combined radiation-trauma injury + positive drug(recombinant human epidermal growth factor) treatment group(JYT group) and combined radiation-trauma injury + pHGF treatment group(HGF group),with 30 rats in each. Immediately after combined radiation-trauma injury was induced,rats in the HGF group were treated with pHGF plasmid,rats in the JYT group with recombinant human epidermal growth factor derivative,and rats in the combined radiation-trauma injury group with PBS. At 3,7,14,21,28 and 35 d post injury,the wound areas were traced,the peripheral blood and the content of hydroxyproline in wound tissue were detected,and pathological examination and capillary count in granulation tissue were performed to study the healingpromoting effect of pHGF on combined radiation-trauma injury in rats. Results The body mass and the count of white blood cells(WBCs) in peripheral blood of rats decreased significantly at 3,28 and 35 d post injury. The relative wound area of the HGF group was smaller or significantly smaller than that of the combined radiation-trauma injury group(P<0.05)within11 days of injury. The content of hydroxyproline in the HGF group was significantly higher than in the JYT group(P<0.05) at 7 and 14 d after injury. The capillary density of granulation tissue in the HGF group was significantly higher than that in the JYT group(P<0.05)at 3 and 7 d after injury,and the capillary density in the HGF group was lower than that in the HGF group(P<0.05) at 14 d after injury. The results of pathological detection showed that in the HGF group the granulation tissue in wound appeared earlier,fibroblasts proliferated actively,granulation tissue and capillaries were more abundant than in the combined radiation-trauma injury group,and t

关 键 词：放创复合伤 肝细胞生长因子 质粒 基因治疗 辐射损伤 细胞外基质 

分 类 号：R818.74[医药卫生—放射医学]