苦参碱对紫外线暴露致大鼠皮肤损伤的保护作用及对CYR61-NF-κB-AP-1通路的影响

职业与健康 ›› 2024, Vol. 40 ›› Issue (20): 2752-2758.

苦参碱对紫外线暴露致大鼠皮肤损伤的保护作用及对CYR61-NF-κB-AP-1通路的影响

李贵宣¹, 曾琳智¹, 蒋亮², 陈剑利²

1.达州市宣汉县人民医院检验科,四川达州 636150;
2.达州市中心医院整形美容烧伤科,四川达州 635000

收稿日期:2023-11-13 修回日期:2024-03-18 出版日期:2024-10-15 发布日期:2026-03-17
通信作者: 陈剑利,主治医师,E-mail：chenjianli1988007@163.com
作者简介:李贵宣,女,主管技师,主要从事医学检验与实验分子生物学工作。
基金资助:
达州市科技项目（18DZYF0014）

Protective effect of matrine on skin damage induced by ultraviolet exposure in rats and its effect on CYR61-NF-κB-AP-1 pathway

LI Guixuan¹, ZENG Linzhi¹, JIANG Liang², CHEN Jianli²

1. Department of Clinical Laboratory,Xuanhan County People's Hospital,Dazhou,Sichuan 636150,China;
2. Department of Plastic Surgery and Burns,Dazhou Central Hospital,Dazhou,Sichuan 635000,China

Received:2023-11-13 Revised:2024-03-18 Online:2024-10-15 Published:2026-03-17
Contact: CHEN Jianli,Attending physician,E-mail: chenjianli1988007@163.com

摘要/Abstract

摘要： 目的探讨苦参碱对紫外线暴露致大鼠皮肤损伤的保护作用及对CYR61-NF-κB-AP-1通路的影响。方法 50只Wistar大鼠随机分为正常对照组、紫外线B（Ultraviolet B,UVB）暴露组、苦参碱低、中、高剂量组;除正常对照组外,其余各组背部脱毛区域进行UVB暴露照射,暴露期间,苦参碱低剂、中、高剂量予以相应药物涂抹干预,正常对照组、UVB暴露组予以等体积的蒸馏水,实验周期为8周,实验结束后,测定大鼠皮肤羟脯氨酸水平、皮肤皱褶评分、皮肤损伤评分、皮肤基质金属蛋白酶-3、皮肤基质金属蛋白酶-9（matrix metalloproteinase,MMP-3,MMP-9）水平、白细胞介素-β（interleukin-β,IL-β）、白细胞介素-6（interleukin-6,IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）、环氧合酶2（cyclooxygenase 2,COX-2）、活性氧（active oxygen,ROS）水平、皮肤半胱氨酸丰富血管生成诱导因子61（cysteine-rich angiogenesis-inducing factor 61,CYR61）、核因子-kappa B（Nuclear factor-kappa B,NF-κB）、激活蛋白-1（activator protein-1,AP-1）mRNA蛋白水平以及皮肤病理结构以及胶原蛋白水平的改变。结果 UVB暴露组、苦参碱低、中、高剂量组羟脯氨酸水平低于正常对照组（P<0.01）,皮肤皱褶评分、皮肤损伤评分、MMP-3水平、MMP-9水平、IL-β、IL-6、TNF-α、COX-2、ROS水平、CYR61、NF-κB、AP-1 mRNA蛋白水平高于正常对照组（均P<0.01）;苦参碱低、中、高剂量组脯氨酸水平高于UVB暴露组（P<0.01）,皮肤皱褶评分、皮肤损伤评分、MMP-3水平、MMP-9、IL-β、IL-6、TNF-α、COX-2、ROS、CYR61、NF-κB、AP-1 mRNA蛋白水平低于UVB暴露组（均P<0.01）,且随着苦参碱剂量的增加,脯氨酸水平逐渐增加（P<0.01）,皮肤皱褶评分、皮肤损伤评分、MMP-3、MMP-9、IL-β、IL-6、TNF-α、COX-2、ROS、CYR61、NF-κB、AP-1 mRNA蛋白水平逐渐降低（均P<0.01）,具有明显剂量依赖性（P<0.01）。正常对照组大鼠皮肤结构正常;UVB暴露组大鼠皮肤厚度明显增加,胶原蛋白密度明显减少,且毛细血管密度减少,炎症细胞浸润明显增加;苦参碱干预后,UVB暴露大鼠皮肤厚度明显减少,胶原蛋白密度明显增多,毛细血管密度增加,炎症细胞浸润减少,且具有明显剂量-效应关系。结论苦参碱对UVB暴露后皮肤损伤具有明显治疗作用,可降低皮肤胶原蛋白降解,同时抑制皮肤氧化应激反应及炎症反应;其机制可能与苦参碱抑制UVB暴露后皮肤CYR61、NF-κB、AP-1 mRNA蛋白的低表达,进而抑制CYR61/NF-κB/AP-1通路的激活有关。

关键词: 苦参碱, 紫外线暴露, 皮肤损伤, 半胱氨酸丰富血管生成诱导因子61, 核因子-kappa B, 激活蛋白-1

Abstract: Objective To investigate the protective effect of matrine on skin damage induced by ultraviolet exposure in rats and its effect on CYR61-NF-κB-AP-1 pathway. Methods Totally 50 Wistar rats were divided into normal control group,Ultraviolet B （UVB） exposure group,matrine low-dose,medium-dose,and high-dose groups. Except for the normal control group,the depilated areas on the back of each group were exposed to UVB. During the exposure period,matrine corresponding drug smear interventions were given at low,medium and high doses of matrine. The normal control group and UVB exposure group were given equal volumes of distilled water. The experimental period was 8 weeks. After the experiment,the skin hydroxyproline level,skin wrinkle score,skin damage score,skin matrix metalloproteinase（MMP-3,MMP-9） level,interleukin-β（IL-β）,interleukin-6（IL-6）,tumor necrosis factor-α（TNF-α）,cyclooxygenase 2（COX-2）,active oxygen（ROS） level,skin cysteine-rich angiogenesis-inducing factor 61（CYR61）,nuclear factor-kappa B（NF-κB）,activator protein-1（AP-1） mRNA protein levels,and changes in skin pathological structure and collagen levels in rats were measured. Results The levels of hydroxyproline in the UVB exposure group,matrine low,medium and high dose groups were lower than those in the normal control group（all P<0.01）,skin fold scores,skin damage scores,MMP-3,MMP-9 levels,IL-β,IL-6,TNF-α,COX-2,ROS levels,CYR61,NF-κB,AP-1 mRNA protein levels were higher than those in the normal control group（all P<0.01）. The proline level in the low,medium and high doses group of matrine were higher than those in the UVB exposure group（all P<0.01）,while the skin fold score,skin damage score,MMP-3,MMP-9,IL-1β,IL-6,TNF-α,COX-2,ROS,CYR61,NF-κB,and AP-1 mRNA protein levels were lower than those in the UVB exposure group（all P<0.01）,and as the dose of matrine increased,the proline level gradually increased（P<0.01）,and skin fold score,skin damage score,MMP-3,MMP-9,IL-1β,IL-6,TNF-α,COX-2,ROS,CYR61,NF-κB,and AP-1 mRNA protein levels gradually decreased（all P<0.01）,with obvious dose dependence（P<0.01）. The skin structure of the normal control group rats was normal,the skin thickness of UVB exposure group rats increased significantly,collagen density decreased significantly,capillary density decreased,and inflammatory cell infiltration increased significantly. After intervention with matrine,the skin thickness of UVB exposure group rats decreased significantly,collagen density increased significantly,capillary density increased,and inflammatory cell infiltration decreased,with a clear dose-effect relationship. Conclusion Matrine has an obvious therapeutic effect on skin damage after UVB exposure,which can reduce the degradation of skin collagen,at the same time inhibit skin oxidative stress and inflammationreactions. The mechanism may be related to the inhibition of low expression of CYR61,NF-κB,and AP-1 mRNA proteins in the skin by matrine after UVB exposure,thereby inhibiting the activation of the CYR61/NF-κB/AP-1 pathway.

Key words: Matrine, Ultraviolet exposure, Skin damage, Cysteine-rich angiogenesis-inducing factor 61, Nuclear factor-kappa B, Activator protein-1

中图分类号:

R-332

李贵宣, 曾琳智, 蒋亮, 陈剑利. 苦参碱对紫外线暴露致大鼠皮肤损伤的保护作用及对CYR61-NF-κB-AP-1通路的影响. [J]职业与健康, 2024, 40(20): 2752-2758.

LI Guixuan, ZENG Linzhi, JIANG Liang, CHEN Jianli. Protective effect of matrine on skin damage induced by ultraviolet exposure in rats and its effect on CYR61-NF-κB-AP-1 pathway. [J]OCCUPATION AND HEALTH, 2024, 40(20): 2752-2758.

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