首页|基于NLRP3/Caspase-1信号通路探讨溃疡油对慢性创面的抗炎促愈作用

基于NLRP3/Caspase-1信号通路探讨溃疡油对慢性创面的抗炎促愈作用

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目的:观察溃疡油对慢性皮肤溃疡新西兰大白兔的创面愈合作用,以及对创面组织核苷酸结合寡聚结构域样受体蛋白3(NLRP3)、天冬氨酸特异性半胱氨酸蛋白酶1(Caspase-1)、核因子κB(NF-κB)表达的影响.方法:将60只新西兰大白兔随机分为空白组(15只)、造模组(45只).采用"激素干预-皮肤缺损-细菌感染"复合因素法复制慢性皮肤溃疡模型,成功后随机分为模型对照组、乳酸依沙吖啶组、溃疡油组,每组15只,分别予0.9%氯化钠溶液、乳酸依沙吖啶、溃疡油干预21 d.分别在干预7、14、21 d时间点检测各组创面面积、创面组织增殖细胞核抗原(PCNA)、NLRP3、Caspase-1、NF-KB p65蛋白表达,以及血常规、肝功能、肾功能等安全性指标.结果:干预7 d时,与模型对照组和乳酸依沙吖啶组比较,溃疡油组创面面积显著减小(P<0.05);与空白组比较,模型对照组PCNA蛋白表达显著降低(P<0.01),NF-κB p65蛋白表达显著增加(P<0.01);与模型对照组和乳酸依沙吖啶组比较,溃疡油组PCNA蛋白表达显著增加(P<0.01);与模型对照组比较,乳酸依沙吖啶组和溃疡油组NF-κB p65蛋白表达均显著降低(P<0.01).干预14 d时,与模型对照组和乳酸依沙吖啶组比较,溃疡油组创面面积显著减小(P<0.01),PCNA蛋白表达显著增加(P<0.05);与模型对照组比较,乳酸依沙吖啶组和溃疡油组NLRP3和NF-KBp65蛋白表达显著降低(P<0.01,P<0.05).干预21 d时,与模型对照组比较,乳酸依沙吖啶组和溃疡油组创面面积均显著减小(P<0.01);与空白组比较,模型对照组PCNA蛋白表达显著降低(P<0.01),NF-κB p65蛋白表达显著增加(P<0.01);与模型对照组和乳酸依沙吖啶组比较,溃疡油组PCNA蛋白表达显著增加(P<0.01);与模型对照组比较,乳酸依沙吖啶组和溃疡油组NF-κB P65蛋白表达显著降低(P<0.05,P<0.01).结论:溃疡油可能通过下调NLRP3/Caspase-1信号通路关键蛋白表达,尤其是NLRP3和NF-κB p65蛋白,以减轻创面炎症反应,同时促进创面组织细胞增殖,进而加速创面愈合,且干预过程中具有良好的安全性.
Exploration on the anti-inflammatory and healing effects of ulcer oil on chronic wounds based on NLRP3/Caspase-1 signaling pathway
Objective:To observe the wound healing effect of ulcer oil on rabbits with chronic skin ulcers and the expression of nucleotide-binding oligodomain-like receptor protein 3(NLRP3),Caspase-1,and nuclear factor-kappa B(NF-κB)in the wound tissue.Methods:A total of 60 New Zealand white rabbits were randomly divided into blank group(n=15)and molded group(n=45).The chronic skin ulcer model was replicated by'hormonal intervention-skin defect-bacterial infection'compound factor method.After success,it was randomly divided into model control group,ethacridine group and ulcer oil group.15 mice in each group were treated with 0.9%sodium chloride solution,ethacridine lactate and ulcer oil for 21 d.Wound area,tissue proliferating cell nuclear antigen(PCNA),NLRP3,Caspase-1,NF-κB p65 protein expression,and blood routine,liver function,kidney function and other safety indicators were detected at intervention 7,14 and 21 d time points.Results:At 7 days of intervention,compared with the model control group and the lactate ethacridine group,the ulcer oil group showed a significant reduction in wound area(P<0.05);Compared with the blank group,the model control group showed a significant decrease in PCNA protein expression(P<0.01)and a significant increase in NF-κB p65 protein expression(P<0.0l);Compared with the model control group and the lactate ethacridine group,the expression of PCNA protein in the ulcer oil group was significantly increased(P<0.01);Compared with the model control group,the NF-κB p65 protein expression was significantly reduced in the lactate ethacridine group and ulcer oil group(P<0.01).At 14 days of intervention,compared with the model control group and the lactate ethacridine group,the ulcer oil group showed a significant decrease in wound area(P<0.01)and a significant increase in PCNA protein expression(P<0.05);Compared with the model control group,the expression of NLRP3 and NF-κB p65 proteins was significantly reduced in the lactate ethacridine group and ulcer oil group(P<0.01,P<0.05).At 21 days of intervention,compared with the model control group,both the lactate ethacridine group and the ulcer oil group showed a significant reduction in wound area(P<0.01);Compared with the blank group,the model control group showed a significant decrease in PCNA protein expression(P<0.01)and a significant increase in NF-κB p65 protein expression(P<0.01);Compared with the model control group and the lactate ethacridine group,the expression of PCNA protein in the ulcer oil group was significantly increased(P<0.01);Compared with the model control group,the NF-κB p65 protein expression was significantly reduced in the lactate ethacridine group and ulcer oil group(P<0.05,P<0.01).Conclusion:Ulcer oil may reduce wound inflammation by downregulating the expression of key proteins in the NLRP3/Caspase-1 signaling pathway,especially NLRP3 and NF-κB p65 proteins,while promoting wound tissue cell proliferation,accelerating wound healing,and having good safety during the intervention process.

Ulcer oilChronic woundNucleotide-binding oligodomain-like receptor protein 3(NLRP3)Caspase-lNuclear factor-kappa B(NF-κB)Anti-inflammationProliferating cell nuclear antigen(PCNA)Wound healing

刘守尧、袁泉、赵芮崧、乔佳君、楼鹏飞、张雨阳、王玥琦、夏仲元

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中日友好医院中医外科,北京 100029

中日友好医院病理科,北京 100029

北京中医药大学,北京 100029

溃疡油 慢性创面 核苷酸结合寡聚结构域样受体蛋白3 Caspase-1 核因子κB 抗炎 增殖细胞核抗原 创面愈合

中日友好医院科研基金青年基金项目北京市中医药科技发展资金项目

2019-1-QN-55JJ-2020-89

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子:1.135
ISSN:1673-1727
年,卷(期):2024.39(9)