新型水凝胶对糖尿病大鼠慢性感染性皮肤创面修复的疗效

Efficacy of new hydrogel for repair of chronic infectious skin wounds in diabetic rats

  • 摘要:
    目的 本研究评估搭载hPTH(3-34)(29-34)短肽的明胶甲基丙烯酸酯(GelMA)水凝胶在糖尿病大鼠慢性感染性皮肤创面愈合中的作用。
    方法 将实验大鼠分为对照组、GelMA组和GelMA+hPTH(3-34)(29-34)组,各15只,制备糖尿病大鼠模型并构建慢性感染性皮肤创面,比较各组在创面面积变化、伤口愈合相关指标Ⅰ型胶原α1链(COL1A1)、α-平滑肌肌动蛋白(α-SMA)、血小板内皮细胞黏附分子-1(CD31)、基质金属蛋白酶-9(MMP9)及环氧合酶-2(Cox2)表达及成纤维细胞体外迁移能力方面的差异。
    结果 与对照组比较,第7、14天GelMA组大鼠创面面积缩小(P<0.05),第3、7、14天GelMA+hPTH(3-34)(29-34)组大鼠创面面积缩小(P<0.05)。与GelMA组相比,第3、7、14天GelMA+hPTH(3-34)(29-34)组大鼠创面面积缩小(P<0.05)。与对照组比较,建模后第7天,大鼠COL1A1、α-SMA及CD31均上调,且GelMA+hPTH(3-34)(29-34)组>GelMA组(P<0.05),而MMP9及Cox2均下调,且GelMA+hPTH(3-34)(29-34)组<GelMA组(P<0.05)。与对照组相比,建模后第7天大鼠NLRP3、IL-6、TNF-α、IL-1β及Caspase-1相对活性均下降,且GelMA+hPTH(3-34)(29-34)组<GelMA组(P<0.05)。建模后第7天大鼠创面组织来源的成纤维细胞相对划痕距离GelMA+hPTH(3-34)(29-34)组>GelMA组>对照组(P<0.05)。
    结论 搭载hPTH(3-34)(29-34)短肽的GelMA水凝胶能通过抑制NLRP3炎症小体通路活性有效加速伤口愈合过程,提升组织修复和结构重建的效果,提升伤口愈合效率的潜力。

     

    Abstract:
    OBJECTIVE This study evaluates the role of Gelation metnacrylate (GelMA) hydrogel loaded with hPTH(3-34)(29-34) short peptide in the healing of chronic infectious skin wounds in diabetic rats.
    METHODS Experimental rats were divided into control group, GelMA group and GelMA+hPTH(3-34)(29-34) group, with 15 rats in each group. Diabetic rat models were prepared, and chronic infectious skin wounds were constructed. Differences in wound area changes, wound healing-related indicator type Ⅰ collagen α1 chain (COL1A1), α-smooth muscle actin (α-SMA), platelet endothelial cell adhesion molecule-1 (CD31), matrix metalloproteinase-9 (MMP9) and cyclooxygenase-2 (Cox2) expression and migration ability of fibroblasts in vitro were compared among the groups.
    RESULTS Compared with the control group, the wound area of rats in the GelMA group decreased on Day 7 and Day 14 (P < 0.05), and the wound area of rats in the GelMA+hPTH(3-34)(29-34) group decreased on Day 3, Day 7 and Day 14 (P < 0.05). Compared with the GelMA group, the wound area of rats in the GelMA+hPTH(3-34)(29-34) group decreased on Day 3, Day 7 and Day 14 (P < 0.05). Compared with the control group, on Day 7 after modeling, the expression of COL1A1, α-SMA and CD31 in rats was upregulated, and in the GelMA+hPTH(3-34)(29-34) group showed a greater increase than in the GelMA group (P < 0.05), while the expression of MMP9 and Cox2 was downregulated, and in the GelMA+hPTH(3-34)(29-34) group showed a greater decrease than in the GelMA group (P < 0.05). Compared with the control group, on Day 7 after modeling, the relative activity of NLRP3, IL-6, TNF-α, IL-1β and Caspase-1 in rats decreased, and in the GelMA+hPTH(3-34)(29-34) group showed a greater decrease than in the GelMA group (P < 0.05). On Day 7 after modeling, the relative scratch distance of fibroblasts derived from the wound tissue in the GelMA+hPTH(3-34)(29-34) group was greater than that in the GelMA group, which was greater than that in the control group (P < 0.05).
    CONCLUSIONS The GelMA hydrogel loaded with hPTH(3-34)(29-34) short peptide can effectively accelerate the wound healing process and enhance tissue repair and structural reconstruction by inhibiting the activity of the NLRP3 inflammasome pathway, demonstrating its potential to improve wound healing efficiency.

     

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