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右美托咪定通过转化生长因子-β1途径对大鼠脊柱切除术后硬膜外纤维化的影响

Effect of dexmedetomidine on epidural fibrosis afterspinal surgery in rats via the transforming growth factor-β1 pathway

    摘要
  • 摘要:
    目的 探讨右美托咪定通过转化生长因子-β1(TGF-β1)信号通路对大鼠脊柱切除术后硬膜外纤维化的影响。
    方法 选取40只大鼠, 将10只大鼠设为对照组; 其余30只构建脊柱切除术后模型，并随机分为模型组、右美托咪定组、右美托咪定+TGF-β1激动剂组，每组10只，剔除建模失败大鼠，最终每组各有9只大鼠纳入后续研究。观察并比较各组大鼠硬膜组织的病理学特征、成纤维细胞数量、PCNA阳性细胞表达率、炎症反应指标白细胞介素(IL)-6、IL-1β、IL-8水平、应激反应指标丙二醛(MDA)、超氧化物歧化酶(SOD)水平及TGF-β1信号通路相关mRNA与蛋白表达量。
    结果 与对照组比较，另外3组的成纤维细胞数量均增加, PCNA阳性细胞表达率均升高，IL-6、IL-1β、IL-8、MDA水平均升高, SOD水平均降低, TGF-β1 mRNA、Smad3 mRNA表达量和TGF-β1、Smad3蛋白表达量均升高，差异有统计学意义(P < 0.05); 与模型组比较，右美托咪定组、右美托咪定+TGF-β1激动剂组的成纤维细胞数量均减少, PCNA阳性细胞表达率均降低，IL-6、IL-1β、IL-8、MDA水平均降低, SOD水平均升高, TGF-β1 mRNA、Smad3 mRNA表达量和TGF-β1、Smad3蛋白表达量均降低，差异有统计学意义(P < 0.05); 与右美托咪定组比较，右美托咪定+TGF-β1激动剂组的成纤维细胞数量增加, PCNA阳性细胞表达率升高, IL-6、IL-1β、IL-8、MDA水平升高, SOD水平降低, TGF-β1 mRNA、Smad3 mRNA表达量和TGF-β1、Smad3蛋白表达量升高，差异有统计学意义(P < 0.05)。
    结论 右美托咪定可通过抑制TGF-β1信号通路，显著减轻大鼠脊柱切除术后的炎症反应和应激反应，减少术后硬膜外纤维化。

     

    Abstract:
    Objective To investigate the impact of dexmedetomidine on epidural fibrosis after spinal surgery in rats through the transforming growth factor-β1 (TGF-β1) signaling pathway.
    Methods A total of 40 rats were selected, with 10 rats assigned to control group. The remaining 30 rats underwent spinal surgery modeling and were randomly divided into model group, dexmedetomidine group, and dexmedetomidine + TGF-β1 agonist group, with 10 rats in each. Rats with unsuccessful modeling were excluded, resulting in 9 rats in each group for subsequent analysis. Pathological characteristics of epidural scar tissue, fibroblast count, PCNA-positive cell expression rate, levels of inflammatory markersinterleukin (IL)-6, IL-1β, IL-8, stress response indicatorsmalondialdehyde (MDA), superoxide dismutase (SOD), and expression levels of mRNAs and proteins related to the TGF-β1 signaling pathway were observed and compared among the groups.
    Results Compared with the control group, the other three groups showed increased fibroblast count, elevated PCNA-positive cell expression rate, higher levels of IL-6, IL-1β, IL-8, and MDA, lower SOD levels, and increased expression levels of TGF-β1 mRNA, Smad3 mRNA, and TGF-β1 and Smad3 proteins, with statistically significant differences (P < 0.05). Compared with the model group, both the dexmedetomidine group and the dexmedetomidine + TGF-β1 agonist group exhibited decreased fibroblast count, reduced PCNA-positive cell expression rate, lower levels of IL-6, IL-1β, IL-8 and MDA, higher SOD levels, and decreased expression levels of TGF-β1 mRNA, Smad3 mRNA, and TGF-β1 and Smad3 proteins, with statistically significant differences (P < 0.05). Compared with the dexmedetomidine group, the dexmedetomidine + TGF-β1 agonist group showed increased fibroblast count, elevated PCNA-positive cell expression rate, higher levels of IL-6, IL-1β, IL-8 and MDA, lower SOD levels, and increased expression levels of TGF-β1 mRNA, Smad3 mRNA, and TGF-β1 and Smad3 proteins, with statistically significant differences (P < 0.05).
    Conclusion Dexmedetomidine can significantly alleviate the inflammatory response and stress response after spinal surgery in rats and reduce postoperative epidural fibrosis by inhibiting the TGF-β1 signaling pathway.

     

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