雷帕霉素及去铁敏对缺血缺氧创面愈合的影响

发布时间：2018-03-02 04:02

本文关键词： 雷帕霉素去铁敏雷帕霉素靶蛋白缺氧诱导因子α 创面愈合　出处：《中国修复重建外科杂志》2017年06期 　论文类型：期刊论文

【摘要】：目的探讨雷帕霉素及去铁敏对缺血缺氧创面愈合的影响及其作用机制。方法 SPF级雄性成年SD大鼠40只,体质量(300±20)g,于背部制备缺血缺氧创面模型;将其随机分为4组(n=10),分别为空白对照组(A组)、去铁敏干预组(B组)、雷帕霉素干预组(C组)、去铁敏+雷帕霉素共同干预组(D组)。模型制备后3、6、9 d,A、B、C、D组分别腹腔注射生理盐水、去铁敏(10 mg/kg)、雷帕霉素(3 mg/kg)、去铁敏(10 mg/kg)+雷帕霉素(3 mg/kg)。模型制备后观察创面愈合情况并记录愈合时间;于创面完全愈合后第2天切取创面愈合组织,采用实时荧光定量PCR及Western blot检测创面组织中雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)、缺氧诱导因子1α(hypoxia inducible factor 1α,HIF-1α)、VEGF m RNA及蛋白的表达。结果各组大鼠均成活至实验完成,创面均愈合;其中A、B、D组创面愈合时间均较C组明显缩短(P0.05);A、B、D组间比较差异无统计学意义(P0.05)。实时荧光定量PCR检测示,C、D组m TOR m RNA表达较A、B组明显下调(P0.05),A、B组间比较差异有统计学意义(P0.05),C、D组间比较差异无统计学意义(P0.05)。B、D组HIF-1α、VEGF m RNA表达较A、C组明显上调,A组较C组表达上调,比较差异有统计学意义(P0.05);B、D组间比较差异无统计学意义(P0.05)。Western blot检测示,C、D组m TOR蛋白相对表达量较A、B组明显下调(P0.05),C、D组间比较差异无统计学意义(P0.05)。A、B、C组HIF-1α蛋白相对表达量明显高于D组(P0.05),A、B、C组间比较差异无统计学意义(P0.05)。B、C、D组VEGF蛋白相对表达量较A组明显下调,D组低于B、C组,C组低于B组,比较差异均有统计学意义(P0.05)。结论去铁敏可促进大鼠缺血缺氧创面愈合,而雷帕霉素作用相反;可能与慢性缺血缺氧创面中存在m TOR与HIF-1信号调节通路有关。
[Abstract]:Objective to investigate the effect and mechanism of rapamycin and deferoxin on wound healing of ischemic and hypoxic wound. Methods 40 adult SD rats of SPF grade, with body weight of 300 卤20 g, were used to establish the model of ischemic and hypoxic wound on the back. They were randomly divided into 4 groups: control group A, desferrin intervention group B, rapamycin intervention group C, destilmicin intervention group D, and normal saline injected intraperitoneally after 3 days, 6 days after the model was made, and 3 days after the model was made, normal saline was injected intraperitoneally in group A, group B, group B, group C, group C, group C, group C, group C, group C, group C, group C, group C, group C, group C, and group C, group C, group C, respectively. 10 mg / kg, rapamycin 3 mg / kg, rapamycin 10 mg / kg) rapamycin 3 mg / kg. The wound healing was observed and the healing time was recorded after the model was made, and the wound healing tissue was removed on the second day after the complete wound healing. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of rapamycin target protein mammalian target of rapamycin TORM, hypoxia inducible factor 1 伪 -hypoxia inducible factor 1 伪 -HIF-1 伪 -VEGFM-VEGF-M RNA and protein in wound tissue. There was no significant difference in wound healing time between group A and C (P 0.05). The expression of m TOR m RNA in group C was significantly lower than that in group A (P 0.05). There was a significant difference in the expression of m TOR m RNA between group A and C by real-time fluorescence quantitative PCR assay (RQFQ), which showed that the expression of m TOR m RNA in group C was significantly lower than that in group A (P 0.05) and the expression of m TOR m RNA in group C was significantly lower than that in group A (P 0.05). There was no significant difference between the two groups. The expression of HIF-1 伪 -VEGFM RNA in group P0.05 was significantly higher than that in group A and C, and the expression of VEGFM in group A was significantly higher than that in group C. There was no significant difference between the two groups. Western blot analysis showed that the relative expression of m TOR protein in group C was significantly lower than that in group A (P 0.05). There was no significant difference in the relative expression of HIF-1 伪 protein between group A and C (P 0.05). ABC group (P 0.05). The relative expression of HIF-1 伪 protein in group B was significantly lower than that in group A (P 0.05). The relative expression of HIF-1 伪 protein in group C was significantly lower than that in group A (P 0.05). There was no significant difference in the relative expression of HIF-1 伪 protein between two groups. The relative expression of VEGF protein in group D was significantly lower than that in group D (P 0.05), and the expression of VEGF protein in group C was lower than that in group B (P < 0.05), and the expression of VEGF protein in group C was lower than that in group B (P < 0.05), and the expression of VEGF protein in group D was significantly lower than that in group A (P 0.05). Conclusion Deferoxamine can promote the wound healing of ischemia and hypoxia in rats, but rapamycin has the opposite effect, which may be related to the existence of m TOR and HIF-1 signal regulation pathway in chronic ischemia and hypoxia wounds.
【作者单位】：遵义医学院附属医院烧伤整形外科;
【基金】：贵州省科学技术基金(黔科合J字[2011]2266号)~~
【分类号】：R622

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