摘要
目的 基于网络药理学分析和动物实验探讨中药滋燥养荣方治疗抗肿瘤靶向药所致皮肤干燥的分子机制。方法采用在线数据库筛选滋燥养荣方各单味药成分的靶点和皮肤干燥及瘙痒的靶点,对共同靶点进行分析,通过通路富集预测中药可能的效应途径。应用靶向药吉非替尼建立与患者皮肤干燥皮损表现一致的大鼠模型,分为模型组、阳性对照组和中药组,分别予生理盐水、维生素E乳、中药进行干预,以正常大鼠作为正常对照组,观察各组皮肤表型、组织病理学变化、信号通路相关蛋白和炎症因子表达。结果 滋燥养荣方各单味药筛选出预测靶点共3 125个,靶向药所致皮肤干燥及伴有瘙痒的对应靶点共660个。对173个共同靶点进行分析,通路富集预测结果显示表皮角质细胞内磷脂酰肌醇-3-激酶(PI3K)-丝苏氨酸蛋白激酶B (Akt)通路可能是中药起效的信号途径。动物实验表明,与正常对照组比较,其余各组均出现靶向药相关的皮损、结痂、脱屑等皮肤干燥表现;与模型组比较,阳性对照组和中药组小鼠的皮肤干燥均改善,中药组小鼠皮损愈合、毛发生长情况优于阳性对照组。与正常对照组比较,模型组表皮增厚(P<0.05);与模型组比较,阳性对照组、中药组表皮厚度变薄(P<0.05)。与正常对照组比较,模型组Akt蛋白和p-Akt 308蛋白染色呈棕黄色,强度较弱;与模型组比较,中药组Akt蛋白和p-Akt 308蛋白染色呈棕黄色,强度较强,且强于阳性对照组,与正常对照组相近。各组p-Akt 473蛋白染色强度差异不明显。Western blotting检测结果:与正常对照组比较,中药组皮肤组织中p-Akt 308蛋白相对表达量低(P<0.05);与模型组比较,中药组皮肤组织中p-Akt 308蛋白相对表达量高(P<0.05)。各组皮肤组织及血清炎症因子水平比较差异无统计学意义(P>0.05)。结论 中药滋燥养荣方能缓解抗肿瘤靶向药所致大鼠局部皮肤炎症、促进皮肤修复,其分子机制可能与Akt相关信号通路有关。
Objective To explore the molecular mechanism of Zizao Yangrong Decoction(ZYD)in treating skin xerosis caused by anti-cancer targeted drugs based on network pharmacological analysis and animal experiments.Methods Online databases were used to search for the corresponding targets of each single herb included in ZYD and skin xerosis and pruritus.The shared targets were analyzed and used to predict the possible effect pathways through pathway enrichment.Rat model consistent with patients'dry skin lesions by targeting drug gefitinib was established,and were divided into model group,positive control group and Chinese herb group,which were treated by normal saline,vitamin E cream,ZYD respectively.Compared with normal rat,the skin phenotype,histopathological changes,the expression of signal pathway-related proteins and inflammation factors were observed.Results Single herb of ZYD was screened out a total of 3125 predicted targets.Targeted drugs-induced skin xerosis which was accompanied by pruritus and caused by targeted drugs was screened out a total of 660 targets.173 targets shared by ZYD and diseases were analyzed.Pathway enrichment showed that PI3K-Akt pathway might be the signal pathway of the effect of ZYD.Animal experiments showed that compared with normal group,rats in other groups developed target drug-related skin xerosis like lesion,scrab and desquamation.Compared with model group,the dryness of skin condition of rats in positive control group and experimental group were improved.The improvement of skin healing and hair growth in experimental group were better than that in positive control group.In the model group,Akt protein and p-Akt 308 protein were stained brown and the intensity was weak.Compared with the model group,Akt protein and p-Akt 308 protein in the Chinese herb group were brown,and the intensity was stronger than that in the positive control group,which was similar to that in the normal control group.There was no significant difference in the staining intensity of p-Akt 473 protein among the groups.Western blotting results:compared with the normal control group,the relative expression of p-Akt 308 protein in the skin tissue of Chinese medicine group was lower(P<0.05);compared with the model group,the relative expression of p-Akt 308 protein in the skin tissue of Chinese herb group was higher(P<0.05).There was no significant difference in the levels of inflammatory factors in skin tissue and serum among the groups(P>0.05).Conclusion Chinese herb ZYD might have a therapeutic effect on targeted drugs-associated skin xerosis by relieving inflammatory reaction and promoting skin recovery,in which Akt-related pathway might be involved.
作者
彭艳梅
王福庆
张旭
李嘉
谭可欣
高亚军
石亚楠
崔慧娟
PENG Yanmei;WANG Fuqing;ZHANG Xu;LI Jia;TAN Kexin;GAO Yajun;SHI Yanan;CUI Huijuan(Department of Oncology,Fangshan Hospital,Beijing University of Chinese Medicine,Beijing 102400,China;Graduate School,Beijing University of Chinese Medicine,Beijing 100029;Department of Integrative Oncology,China-Japan Friendship Hospital,Beijing 100029)
出处
《北京中医药》
2024年第6期645-654,共10页
Beijing Journal of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(82104879)
北京中医药大学2020年新教师启动基金项目(2020-BUCMXJKY003)。
关键词
滋燥养荣方
靶向药
皮肤干燥
网络药理学
大鼠
分子机制
Zizao Yangrong Formula
targeted drugs
skin xerosis
network pharmacology
rat
molecular mechanisms
