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紫榆膏调控Ras/Raf/ERK通路对肛周脓肿大鼠术后创面愈合的影响机制
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| 篇名： | 紫榆膏调控Ras/Raf/ERK通路对肛周脓肿大鼠术后创面愈合的影响机制 |
| TITLE： | Mechanism of Ziyu ointment in regulating the Ras/Raf/ERK signaling pathway to influence the postoperative wound healing in rats with perianal abscess |
| 摘要： | 目的 基于Ras/Raf蛋白激酶（Raf）/胞外信号调节激酶（ERK）信号通路，研究紫榆膏对肛周脓肿大鼠术后创面愈合的影响机制。方法将大鼠随机分为对照组、模型组、凡士林组（即阳性对照组，25mg/cm2）、紫榆膏组（25mg/cm2）、紫榆膏+PD98059（ERK抑制剂）组（25mg/cm2紫榆膏+300μg/LPD98059溶液10μL），每组12只。各组大鼠背部切圆形切口，除对照组外，均滴加粪便上清液以复制肛周脓肿模型。造模成功后，给药组大鼠涂抹相应药物，每天1次，连续14d。测量大鼠给药第0、7、14d时的创面面积，并计算创面愈合率；检测大鼠血清中炎症因子[肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）]和生长因子[碱性成纤维细胞生长因子（bFGF）、表皮生长因子（EGF）]水平；观察大鼠创面组织病理学形态；免疫组化法检测大鼠创面组织中分化簇34（CD34）、血管内皮生长因子（VEGF）表达水平；Westernblot法检测大鼠创面组织中Ras/Raf/ERK信号通路相关蛋白表达水平。结果与对照组比较，模型组大鼠给药第7、14d时的创面愈合率，血清中bFGF、EGF水平，创面组织中新生毛细血管数和CD34、VEGF、Ras、Raf1、ERK1、ERK2表达水平均显著降低/减少（P＜0.05）；血清中TNF-α、IL-6水平均显著升高（P＜0.05）；创面组织病理损伤严重，表皮变薄，只有少量肉芽形成。与模型组比较，紫榆膏组、凡士林组大鼠上述定量指标水平均显著改善（P＜0.05）；创面组织病理损伤明显改善，表皮增厚，有大量新生毛细血管和肉芽形成。与紫榆膏组比较，紫榆膏+PD98059组大鼠上述大部分定量指标水平均显著逆转（P＜0.05），创面组织病理损伤明显加重。结论紫榆膏可减轻肛周脓肿大鼠术后创面炎症反应，促进血管生成和创面愈合，其作用机制可能与激活Ras/Raf/ERK信号通路活性有关。 |
| ABSTRACT： | OBJECTIVE To explore the effects of Ziyu ointment on postoperative wound healing in rats with perianal abscess based on Ras/Raf protein kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway. METHODS The rats were randomly divided into control group， model group， vaseline treatment group （positive control group， 25 mg/cm2）， Ziyu ointment group （25 mg/cm2）， Ziyu ointment+PD98059 （ERK inhibitor） group （25 mg/cm2 Ziyu ointment+300 μg/L PD98059 solution 10 μL）， with 12 rats in each group. A circular incision was made on the backs of rats in each group. Except for the control group， fecal supernatant was applied dropwise to induce the perianal abscess model. After successful modeling， corresponding drugs were applied topically to rats in administration group， once a day， for 14 consecutive days. The wound areas of the rats were measured on days 0， 7 and 14 of drug administration， and the wound healing rates were calculated. The levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）] and growth factors [basic fibroblast growth factor （bFGF）， epidermal growth factor （EGF）] in the serum of the rats were detected. The histopathological morphology of the wound tissues in the rats was also observed. Immunohistochemistry was used to detect the expressions of cluster of differentiation 34 （CD34） and vascular endothelial growth factor （VEGF） in the wound tissues of rats. Western blot was used to detect the expressions of the proteins related to the Ras/Raf/ERK signaling pathway in the wound tissues of rats. RESULTS Compared with control group， the wound healing rates on days 0， 7 and 14 of drug administration， serum levels of bFGF and EGF， the number of newly formed capillaries in the wound tissues， and the expression levels of CD34， VEGF， Ras， Raf1， ERK1 and ERK2 in the wound tissues of rats in the model group were all significantly decreased （P＜0.05）； however， serum levels of TNF-α and IL-6 were all significantly increased （P＜0.05）. The histopathological damage to the wound tissue was severe， with a thinned epidermal layer and only a small amount of granulation tissue formation. Compared with model group， the levels of the aforementioned quantitative indicators in rats from the Ziyu ointment group and vaseline group were significantly improved （P＜0.05）. The histopathological damage to the wound tissue was notably ameliorated， with increased epidermal thickness and the formation of a substantial number of newly formed capillaries and granulation tissue. Compared with Ziyu ointment group， the levels of most of the aforementioned quantitative indicators in rats from the Ziyu ointment+PD98059 group were significantly reversed （P＜0.05）， the histopathological damage to the wound tissue was markedly aggravated. CONCLUSIONS Ziyu ointment may alleviate the postoperative inflammatory response in the wound of rats with perianal abscess， promote angiogenesis and wound healing. Its mechanism of action may be related to the activation of the Ras/Raf/ERK signaling pathway. |
| 期刊： | 2025年第36卷第21期 |
| 作者： | 陈月；封三花；陈善虎 |
| AUTHORS： | CHEN Yue，FENG Sanhua，CHEN Shanhu |
| 关键字： | 紫榆膏；Ras/Raf/ERK信号通路；肛周脓肿；创面愈合；血管生成 |
| KEYWORDS： | Ziyu ointment； Ras/Raf/ERK signaling pathway； perianal abscess； wound healing； angiogenesis |
| 阅读数： | 1 次 |
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