紫草素通过上调C-X-C基序趋化因子受体4促进细胞自噬加快糖尿病创面愈合的机制研究

doi:10.3760/cma.j.cn115791-20230919-00174

科研成果详情

题名	紫草素通过上调C-X-C基序趋化因子受体4促进细胞自噬加快糖尿病创面愈合的机制研究
其他题名	Study on the mechanism of shikonin promoting autophagy and accelerating wound healing in diabetic rats through upregulating C-X-C chemokine receptor type 4
作者	徐捷 1; 金利泰2,4; 王涛 3; 童芸 1; 张帆4; 林熳熳 1; 张梓凯 1
发表日期	2024-01-20
发表期刊	中华糖尿病杂志影响因子和分区
语种	中文
原始文献类型	Periodical
关键词	紫草素 C-X-C基序趋化因子受体4 糖尿病溃疡细胞自噬创面愈合
其他关键词	Shikonin ; C-X-C motif chemokine receptor 4 ; Diabetic ulcers ; Cell autophagy ; Wound healing
摘要	目的:探讨紫草素是否通过上调C-X-C基序趋化因子受体4（CXCR4）的表达调控细胞自噬促进糖尿病大鼠创面愈合。方法:将24只Sprague-Dawley（SD）大鼠按照随机数字表法分成4组：对照组、糖尿病组、糖尿病+紫草素组和糖尿病+紫草素+干扰CXCR4的短发卡RNA（sh-CXCR4）组，每组6只。通过腹腔注射链脲佐菌素构建糖尿病大鼠模型，利用直径为1 cm的皮肤打孔器在大鼠背部建立溃疡模型。分别于创伤后第0、7、14和21天计算创面愈合率。于创伤后第21天，采集皮肤组织，进行HE染色和Masson染色分析创面病理变化，采用CD31免疫组织化学法分析创面微血管密度以及Western blotting法检测创面组织CXCR4和细胞自噬相关蛋白微管相关蛋白1轻链3（LC3）Ⅱ/LC3Ⅰ、Beclin1和可溶性p62蛋白的相对表达量，透射电镜观察自噬小体。组间比较采用单因素方差分析。结果:与对照组相比，糖尿病组大鼠创面愈合率（第21天分别为72.44%±6.21%和93.71%±6.76%）、创面组织新生血管和胶原沉积、微血管密度以及创面组织中CXCR4和细胞自噬相关蛋白LC3Ⅱ/LC3Ⅰ和Beclin1水平及自噬小体数量降低，而p62水平升高，差异均具有统计学意义（ P<0.05）。与糖尿病组比较，糖尿病+紫草素组大鼠创面愈合率（第21天分别为86.74%±4.86%和72.44%±6.21%）、创面组织新生血管、胶原沉积情况、微血管密度、创面组织中CXCR4和LC3Ⅱ/LC3Ⅰ和Beclin1水平及自噬小体数量升高，而p62水平降低，差异均具有统计学意义（ P<0.05）。与糖尿病+紫草素组比较，糖尿病+紫草素+sh-CXCR4组大鼠创面愈合率（第21天分别为76.15%±3.85%和86.74%±4.86%）、创面组织新生血管、胶原沉积情况、微血管密度、创面组织中CXCR4、LC3Ⅱ/LC3Ⅰ和Beclin1水平及自噬小体数量降低，而p62水平升高，差异具有统计学意义（ P<0.05）。结论:紫草素通过上调CXCR4的表达并激活细胞自噬，促进糖尿病溃疡创面的愈合。
其他摘要	Objective:To investigate whether shikonin can regulate autophagy and promote wound healing in diabetic rats by upregulating C-X-C chemokine receptor type 4 (CXCR4).Methods:A total of 24 Sprague-Dawley (SD) rats were assigned to control, diabetic, diabetic+Shikonin, and diabetic+Shikonin+sh-CXCR4 groups (6 rats in each group) using random number table method. A diabetic rat model was established by intraperitoneal injection of streptozotocin, and a 1 cm-diameter skin punch was used to create an ulcer model on the back of the rat. Wound healing rates were calculated on days 0, 7, 14, and 21 after wounding. On day 21 after wounding, skin tissues were collected for hematoxylin & eosin and Masson trichrome staining to analyze the pathological changes of the wound. CD31 immunohistochemistry was performed to analyze the microvascular density of the wound and Western blotting was used to detect the expression of CXCR4 and cell autophagy-related proteins microtubule-related proteins light chain 3 (LC3)Ⅱ/LC3Ⅰ, Beclin1, and soluble p62 in the wound tissue. Autophagosomes were observed by transmission electron microscopy. One-way analysis of variance was used for comparison between groups.Results:Compared with the control group, the diabetic group had reduced wound healing rate (on day 21: 72.44%±6.21% vs. 93.71%±6.76%), neovascularization, collagen deposition, microvascular density, levels of CXCR4, LC3Ⅱ/LC3Ⅰ, and Beclin, and increased p62 levels in the wound tissue, as well as decreased autophagosomes ( P<0.05). Compared with the diabetic group, wound healing rate (on day 21: 86.74%±4.86% vs. 72.44%±6.21%), neovascularization, collagen deposition, microvascular density, levels of CXCR4, LC3Ⅱ/LC3Ⅰ, and Beclin, and autophagosomes were increased, but p62 levels were decreased in the diabetic+Shikonin group ( P<0.05). Compared with the diabetic+Shikonin group, the diabetic+Shikonin group had decreased wound healing rate (on day 21: 76.15%±3.85% vs. 86.74%±4.86%), neovascularization, collagen deposition, microvascular density, levels of CXCR4, LC3Ⅱ/LC3Ⅰ, and Beclin, and autophagosomes in the wound tissue, as well as increased p62 levels ( P<0.05). Conclusion:Shikonin promotes the healing of diabetic ulcer wounds by upregulating CXCR4 expression and activating cell autophagy.
资助项目	National Natural Science Foundation of China[82205109]
出版者	Chinese Medical Journals Publishing House Co.Ltd
ISSN	1674-5809
卷号	16 期号:1 页码:84-91
DOI	10.3760/cma.j.cn115791-20230919-00174
页数	8
收录类别	万方 ; SCOPUS ; CSCD ; ISTIC ; 北大核心
URL	查看原文
SCOPUSEID	2-s2.0-85185598378
通讯作者地址	[Xu, Jie]Plastic and Cosmetic Center,Affiliated Jinhua Hospital,Zhejiang University School of Medicine,Jinhua,321000,China
Scopus学科分类	Internal Medicine;Endocrinology, Diabetes and Metabolism
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/214899
专题	药学院（分析测试中心）附属第一医院附属第一医院_皮肤科
作者单位	1.浙江大学医学院附属金华医院整形美容中心，金华　321000; 2.温州医科大学药学院，温州　325000; 3.广州中医药大学第一附属医院胃肠外科，广州　510080; 4.温州医科大学附属第一医院皮肤科，温州　325000
推荐引用方式 GB/T 7714	徐捷,金利泰,王涛,等. 紫草素通过上调C-X-C基序趋化因子受体4促进细胞自噬加快糖尿病创面愈合的机制研究[J]. 中华糖尿病杂志,2024,16(1):84-91.
APA	徐捷., 金利泰., 王涛., 童芸., 张帆., ... & 张梓凯. (2024). 紫草素通过上调C-X-C基序趋化因子受体4促进细胞自噬加快糖尿病创面愈合的机制研究. 中华糖尿病杂志, 16(1), 84-91.
MLA	徐捷,et al."紫草素通过上调C-X-C基序趋化因子受体4促进细胞自噬加快糖尿病创面愈合的机制研究".中华糖尿病杂志 16.1(2024):84-91.