基于FAK/PI3K/Akt/mTOR信号通路探讨五倍子鞣质乳膏促进大鼠的皮肤伤口愈合作用机制  

Mechanism of tannins from Galla chinensis cream in promoting skin wound healing in rats based on FAK/PI3K/Akt/mTOR signaling pathway

作　　者：易文[1] 颜紫依 石孟琼[2] 张颖[3] 刘杰[3] 易倩 唐海明 刘义稳 YI Wen;YAN Zi-yi;SHI Meng-qiong;ZHANG Ying;LIU Jie;YI Qian;TANG Hai-ming;LIU Yi-wen(the First College of Clinical Medical Science,China Thress Gorges University,Yichang Central People's Hospital,Yichang 443000,China;Basic Medical College of China Three Gorges University,Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy,Yichang 443002,China;Hubei Key Laboratory of Natural Products Research and Development,China Three Gorges University,Yichang Laboratory of Development and Utilization of Health Products with Drug and Food Homology,Yichang 443002,China;Hubei Heng'an Fulin Pharmaceutical Co.,Ltd.,Yichang 443199,China;Wufeng Chicheng Biotechnology Co.,Ltd.,Yichang 443413,China)

机构地区：[1]三峡大学第一临床医学院,宜昌市中心人民医院,湖北宜昌443000 [2]三峡大学基础医学院,肿瘤微环境与免疫治疗湖北省重点实验室,湖北宜昌443002 [3]三峡大学天然产物研究与利用湖北省重点实验室,药食同源大健康产品开发利用宜昌市重点实验室,湖北宜昌443002 [4]湖北恒安芙林药业股份有限公司,湖北宜昌443199 [5]五峰赤诚生物科技股份有限公司,湖北宜昌443413

出　　处：《中国中药杂志》2025年第2期480-495,共16页China Journal of Chinese Materia Medica

基　　金：湖北省省卫计委中医药科研立项项目(ZY2021M011);湖北省科技厅重点研发大健康计划项目(2022BCE017);湖北省自然科学基金项目(2023AFB600,2022CFB357,2022CFB427);湖北省卫生健康委员会中医药重点项目(ZY2023Z015);湖北卫生健康委员会卫生健康科研项目(WJ2023M153);湖北省宜昌市科学技术局医疗卫生研究项目(A23-1-061);湖北省功能性消化系统疾病中医临床医学研究中心开放基金项目(SXZ202303,SXZ202308,SXZ202311)。

摘　　要：研究五倍子鞣质乳膏(tannins from Galla chinensis cream,TGCC)对大鼠鼠尾皮肤伤口的影响及作用机制。将雄性SD大鼠随机分为空白(control)组、模型(model)组、model+TGCC低剂量(每只50 mg)组、model+TGCC高剂量(每只100 mg)组和model+TGC+FAK抑制剂(Y15)乳膏(每只100 mg+10 mg)组,每组10只。在成功构建鼠尾皮肤损伤模型后,给药组在其创面分别涂抹相应的药物,control组和model组以同样方法分别涂抹与TGCC组相同量的乳膏基质,涂抹完成后在伤口周缘包扎无菌纱布。每天3次,连续28 d。记录在干预3、7、11、14、21、28 d创面愈合情况,计算伤口愈合率和愈合时间。末次给药次日收集大鼠血清与鼠尾皮肤伤口组织进行血清中丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、肌酐(creatinine,CREA)、尿素、活性氧(reactive oxygen species,ROS)、干扰素-γ(interferon-γ,IFN-γ)、白细胞介素(interleukin,IL)-1β、IL-6、IL-4、IL-10、肿瘤坏死因子(tumor necrosis factor,TNF)-α及鼠尾皮肤伤口组织中过氧化氢酶(catalase,CAT)、谷胱甘肽(glutathione,GSH)、乳酸脱氢酶(lactate dehydrogenase,LDH)、丙二醛(malondialdehyde,MDA)、髓过氧化物酶(myeloperoxidase,MPO)、超氧化物歧化酶(superoxide dismutase,SOD)、总抗氧化能力(total antioxidant capacity,T-AOC)、血小板内皮细胞黏附分子-1(platelet endothelial cell adhesion molecule-1,CD31)、白细胞分化抗原34(leukocyte differentiation antigen 34,CD34)的活性检测,苏木精-伊红、Masson和天狼猩红染色观察鼠尾皮肤伤口组织组织形态学改变,计算表皮厚度、成纤维细胞数、血管数量、胶原纤维、Ⅰ型胶原纤维(typeⅠcollagen,COLⅠ)、COLⅢ含量;实时荧光定量PCR法检测皮肤伤口组织中角蛋白(keratin,KRT)10、KRT14、血管内皮生长因子(vascular endothelial growth factor,VEGF)、成纤维细胞生长因子(fibroblast growth factor,FGF)、表皮�This study investigated the effects and action mechanism of tannins from Galla chinensis cream(TGCC)on the skin wound of rat tail.Male Sprague Dawley(SD)rats were randomly divided into a control group,model group,model+low-dose TGCC(50 mg per rat)group,model+high-dose TGCC group(100 mg per rat),and model+TGC+FAK inhibitor(Y15)cream(100 mg+10 mg per rat)group,with 10 rats in each group.After the rat tail skin injury model was successfully constructed,in the treatment group,corresponding drugs were applied to the wound surface,while in the control and model groups,the same amount of cream base as the TGCC group was applied by the same method.Then,sterile gauze was wrapped around the wound edge,and these operations were performed three times a day for 28 consecutive days.The wound healing status at the third,seventh,eleventh,fourteenth,twenty-first,and twenty-eighth days was recorded,and the wound healing rate and healing time were calculated.On the day after the last dose of medication,rat serum and tail skin wound tissue were collected for analyzing the activities of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(CREA),urea,reactive oxygen species(ROS),interferon gamma(IFN-γ),interleukin(IL)-1β,IL-6,IL-4,IL-10,tumor necrosis factor(TNF)-α,as well as catalase(CAT),glutathione(GSH),lactate dehydrogenase(LDH),malondialdehyde(MDA),myeloperoxidase(MPO),superoxide dismutase(SOD),total antioxidant capacity(T-AOC),platelet endothelial cell adhesion molecule-1(CD31),and leukocyte differentiation antigen 34(CD34)in the wound tissue of rat tail skin.Hematoxylin-eosin,Masson,and sirius red staining were used to observe the morphological changes in the wound tissue of rat tail skin.The thickness of the epidermis,the number of fibroblasts and blood vessels,and the contents of collagen fibers,typeⅠcollagen(COLⅠ),and COLⅢwere calculated.The mRNA expressions of keratin 10(KRT10),KRT14,vascular endothelial growth factor(VEGF),fibroblast growth factor(FGF),epidermal growth factor(EGF),CD31,CD

关 键 词：五倍子鞣质乳膏 氧化损伤 炎症反应 黏着斑激酶/磷脂酰肌醇-3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路 

分 类 号：R73[医药卫生—肿瘤]