青蒿琥酯通过抑制Stat3/TGF-β1信号通路改善大鼠头颈放射性皮肤纤维化的实验研究  

Experimental study of artesunate ameliorating head-and-neck radiation-induced skin fibrosis in rats through inhibiting Stat3/TGF-β1 signaling pathway

作　　者：唐婵 欧剑波[1] 农晓琳[1] TANG Chan;OU Jianbo;NONG Xiaolin(College&Hospital of Stomatology,Guangxi Medical University,Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Recontrolstruction,Nanning 530021,China)

机构地区：[1]广西医科大学口腔医学院/附属口腔医院广西口腔颌面修复与重建研究重点实验室,南宁530021

出　　处：《广西医科大学学报》2025年第2期226-232,共7页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81060156);广西自然科学基金面上项目资助(No.2024GXNSFAA010359)。

摘　　要：目的:研究青蒿琥酯(ART)改善大鼠头颈部放射治疗引发的放射性皮肤纤维化(RISF)的作用及机制。方法:30只SD大鼠随机分为3组:正常对照组、单纯放射组、ART干预组,每组10只。通过医用直线电子加速器一次性照射18 Gy构建大鼠头颈部放射治疗模型,干预组于放射造模前3 d使用ART(20 mg/kg)灌胃,每日1次,持续4周。造模后12周处死取材,苏木精—伊红(HE)染色、Masson及免疫组化染色观察大鼠放射区皮肤组织病理情况、真皮厚度改变以及α-SMA蛋白在皮肤组织中的表达情况;实时荧光定量聚合酶链式反应(RT-qPCR)检测Stat3、TGF-β1、IL-6 mRNA表达情况;蛋白质免疫印迹法(western blotting)检测p-Stat3、Stat3、TGF-β1、α-SMA、IL-6的蛋白表达水平。结果:ART干预可减轻头颈部放疗大鼠的皮肤外观损伤、病理学损伤,改善真皮厚度与胶原沉积(P<0.05),减少放疗后大鼠皮肤组织中α-SMA的表达;显著下调p-Stat3/Stat3、TGF-β1、IL-6的蛋白及mRNA表达水平(P<0.05)。结论:ART可改善大鼠头颈部放射治疗后出现的RISF,其作用机制可能与下调Stat3/TGF-β1信号通路进而抑制炎症有关。Objective:To study the effect and mechanism of artesunate(ART)in improving radiation-induced skin fibrosis(RISF)induced by head-and-neck radiotherapy in rats.Methods:Thirty Sprague-Dawley rats were randomly divided into three groups:a control group,an irradiation only group(IR group),and an ART intervention group(ART+IR group),with 10 rats in each group.A rat model of head-and-neck radiotherapy was established by using medical linear electron accelerator with a single dose of 18 Gy.The ART+IR group was administered ART(20 mg/kg)intragastrically once a day,3 days prior to radiation and continued for 4 weeks.Twelve weeks after the model establishment,rats were sacrificed and tissue collected.Hematoxylin-eosin(HE)staining,Masson staining and immunohistochemical staining were used to observe the histopathological condition of the skin tissue in the irradiated area of the rats,the changes of the dermal thickness,and the expression ofα-SMA protein in the skin tissue;the mRNA expression of Stat3,TGF-β1,and interleukin-6(IL-6)was detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR);the western blotting was used to detect the protein expression of p-Stat3,Stat3,TGF-β1,α-SMA,and IL-6.Results:ART intervention reduced skin appearance damage,pathological damage,improved dermal thickness and collagen deposition in head-and-neck radiotherapy rats(P<0.05),and reducedα-SMA expression in skin tissue of rats after radiotherapy;it significantly downregulated the protein and mRNA expression levels of p-Stat3/Stat3,TGF-β1,and IL-6(P<0.05).Conclusion:ART can improve RISF after head-and-neck radiotherapy in rats,and its mechanism may be related to the downregulation of Stat3/TGF-β1 signaling pathway and thus inhibit inflammation.

关 键 词：放射性皮肤纤维化 青蒿琥酯 Stat3/TGF-β1 

分 类 号：R285.5[医药卫生—中药学]