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海洋中药氢化珊瑚钙防治化疗药物外渗性皮肤溃疡的实验研究
廖心怡1,潘雅婷1,唐美霞1,邓娅婷1,徐家华1,于观贞1,2*
0
(1. 上海中医药大学附属龙华医院肿瘤科, 上海 200032;
2. 浙江数字内容研究院数字医疗与人工智能实验室, 绍兴 312366
*通信作者)
摘要:
目的 探讨海洋中药氢化珊瑚钙对表柔比星所致小鼠皮肤外渗性溃疡的防护作用,为海洋中药氢化珊瑚钙的临床应用提供依据。方法 建立表柔比星所致小鼠皮肤外渗性溃疡模型,将模型小鼠分为对照组(予以基础处理及生理盐水冲洗)和实验组(除予以基础处理及生理盐水冲洗外,另予以早、中、晚氢化珊瑚钙0.375 g/cm2局部均匀涂抹创口各1次)。观察并记录对照组及实验组小鼠的皮肤外渗性溃疡面积、程度和愈合时间。在连续用药15 d后,切除溃疡组织,用H-E染色观察病理形态学改变,免疫组织化学染色检测溃疡部位皮肤及皮下组织中Ki-67和氧化应激相关指标血红素加氧酶1(HO-1)、烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NOX2)、诱导型一氧化氮合酶2(iNOS2)和超氧化物歧化酶1(SOD1)的表达情况。结果 对照组小鼠的皮肤外渗性溃疡发生率为100.0%(5/5),而实验组为60.0%(3/5)。实验组的溃疡面积小于对照组(P<0.05),愈合速度快于对照组。H-E染色显示对照组小鼠皮下结缔组织增生、组织结构紊乱、毛囊扩张、鳞状上皮增厚,而实验组小鼠皮下组织结构稍显紊乱、少见毛囊扩张、鳞状上皮稍厚。免疫组织化学染色显示实验组小鼠皮下组织中Ki-67表达强于对照组,对照组中iNOS2、NOX2的表达高于实验组(P均<0.05),对照组中HO-1、SOD1的表达低于实验组(P均<0.05)。结论 海洋中药氢化珊瑚钙对表柔比星外渗所致的皮肤溃疡有良好的防护作用。
关键词:  海洋中药  氢化珊瑚钙  表柔比星  化疗药物外渗  外渗性溃疡
DOI:10.16781/j.CN31-2187/R.20230017
投稿时间:2023-01-18修订日期:2023-07-10
基金项目:上海中医药大学附属龙华医院高层次人才引进项目(LH02.51.002),上海市大学生创新创业训练计划项目(S202110268118).
Prevention and treatment of chemotherapeutic extravasation skin ulcer with marine traditional Chinese medicine coral calcium hydride: an experimental study
LIAO Xinyi1,PAN Yating1,TANG Meixia1,DENG Yating1,XU Jiahua1,YU Guanzhen1,2*
(1. Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China;
2. Laboratory of Digital Health and Artificial Intelligence, Zhejiang Digital Content Research Institute, Shaoxing 312366, Zhejiang, China
*Corresponding author)
Abstract:
Objective To investigate the protective effect of marine traditional Chinese medicine coral calcium hydride on skin extravasation ulcer induced by epirubicin in mice, so as to provide basis for the clinical application of coral calcium hydride. Methods The mouse skin exosmotic ulcer model created by epirubicin was established. Then the mice were divided into control group (treated with routine treatment and normal saline irrigation) and experimental group (treated with routine treatment and 0.375 g/cm2 coral calcium hydride in the early, middle, and late of the day, respectively). The area, degree, and healing time of exosmotic ulcer of model animals in the 2 groups were observed and recorded. After continuous treatment for 15 d, the ulcer tissue was resected and the pathomorphological changes were observed by hematoxylin-eosin (H-E) staining. The expression of Ki-67, oxidative stress-related indexes heme oxygenase 1 (HO-1), nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), inducible nitric oxide synthase 2 (iNOS2), and superoxide dismutase 1 (SOD1) in the skin and subcutaneous tissue was detected by immunohistochemistry. Results The incidence of exosmotic ulcer was 100.0% (5/5) in the control group and 60.0% (3/5) in the experimental group. The ulcer area of the experimental group was significantly less than that of the control group (P<0.05), and the ulcer healing speed was significantly faster than that of the control group. H-E staining showed that the subcutaneous connective tissue was disordered, with hair follicle dilated and squamous epithelium thickened in the control group, while the subcutaneous tissue in the experimental group was slightly disordered, with dilated hair follicle rarely seen and thickened squamous epithelium. Immunohistochemistry showed that the expression of Ki-67 in subcutaneous tissue of the experimental group was higher than that of the control group, the expression of iNOS2 and NOX2 in the control group was significantly higher than that of the experimental group (bothP<0.05), and the expression of HO-1 and SOD1 in the control group was significantly lower than that of the experimental group (both P<0.05). Conclusion Marine traditional Chinese medicine coral calcium hydride has a good protective effect on skin ulcer caused by epirubicin extravasation.
Key words:  marine traditional Chinese medicine  coral calcium hydride  epirubicin  extravasation of chemotherapeutic drugs  extravasated ulcer