外源性碱性成纤维细胞生长因子促进大鼠创面愈合的机制  

Mechanism by which exogenous basic fibroblast growth factor promotes wound healing in rats

作　　者：李振超[1] 杜喜玲[2] 韩志新 牛大伟 樊昌伟 Li Zhenchao;Du Xiling;Han Zhixin;Niu Dawei;Fan Changwei(Department of Orthopedics and Burn,Anyang People’s Hospital,Anyang 455000,Henan Province,China;Hebi Polytechnic,Hebi 458000,Henan Province,China)

机构地区：[1]安阳市人民医院整形烧伤科,河南省安阳市455000 [2]鹤壁职业技术学院,河南省鹤壁市458000

出　　处：《中国组织工程研究》2025年第11期2243-2251,共9页Chinese Journal of Tissue Engineering Research

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20230855),项目负责人:韩志新;安阳市科技攻关计划项目(2023C01SF149),项目负责人:韩志新。

摘　　要：背景:深入揭示外源性碱性成纤维细胞生长因子促进创面愈合的分子机制。目的:探讨外源性碱性成纤维细胞生长因子对大鼠创面修复中巨噬细胞表型转换和肉芽再生的影响。方法:(1)体外细胞实验:分为正常对照组、低剂量碱性成纤维细胞生长因子组、高剂量碱性成纤维细胞生长因子组以及碱性成纤维细胞生长因子+丙戊酸组,其中低、高剂量碱性成纤维细胞生长因子组细胞培养基中分别添加100,200μg/L碱性成纤维细胞生长因子,碱性成纤维细胞生长因子+丙戊酸组细胞培养基中添加200μg/L碱性成纤维细胞生长因子和20 mmol/L Notch1/Jagged1激动剂丙戊酸。通过EdU实验、划痕实验、小管生成实验检测碱性成纤维细胞生长因子对人脐静脉内皮细胞增殖、迁移和血管新生的影响。(2)体内动物实验:SD大鼠按照随机数字表法分为模型组、低剂量碱性成纤维细胞生长因子组、高剂量碱性成纤维细胞生长因子组以及碱性成纤维细胞生长因子+丙戊酸组,构建大鼠全层皮肤缺损开放性创面模型,其中低、高剂量碱性成纤维细胞生长因子组皮下注射100,200μg/L碱性成纤维细胞生长因子,碱性成纤维细胞生长因子+丙戊酸组大鼠皮下注射200μg/L碱性成纤维细胞生长因子的同时腹腔注射10 mg/kg丙戊酸。给药7,14 d检测大鼠创面的愈合率;TUNEL检测创面组织中的细胞凋亡情况;酶联免疫吸附实验检测大鼠血清中丙二醛、超氧化物歧化酶、肿瘤坏死因子α和白细胞介素10水平;免疫荧光检测创面组织中巨噬细胞的表型转换情况;免疫组化检测创面组织中增殖细胞核抗原、CD31和血管内皮生长因子的表达;Western blot法检测创面组织中Notch1、Jagged1的表达。结果与结论:(1)与正常对照组相比,碱性成纤维细胞生长因子能明显促进人脐静脉内皮细胞的增殖、迁移和血管新生,并且具有剂量依赖性;(2)与模型�BACKGROUND:This study provided insight into the molecular mechanisms by which exogenous basic fibroblast growth factor(bFGF)promotes wound healing.OBJECTIVE:To investigate the effect of exogenous bFGF on macrophage phenotype transition and granulation regeneration during wound repair in rats.METHODS:(1)In vitro experiment:Cells were divided into normal control group,low-dose bFGF group,high-dose bFGF group,and bFGF+valproic acid group.100 and 200μg/L bFGF was added into the cell culture medium of low-dose bFGF group and high-dose bFGF group,respectively,while 200μg/L bFGF and 20 mmol/L valproic acid were added into the cell culture medium of valproic acid group.EdU test,scratch test and tubule formation test were used to detect the effects of bFGF on proliferation,migration and angiogenesis of human umbilical vein endothelial cells.(2)In vivo experiment:Sprague-Dawley rats were randomly divided into model group,low-dose bFGF group,high-dose bFGF group and bFGF+valproic acid group.The open wound model of full-thickness skin defect was established in low-dose bFGF group,high-dose bFGF group and bFGF+valproic acid group.Rats in the low-and high-dose bFGF groups were given 100 and 200μg/L bFGF through subcutaneous injection,while those in the bFGF+valproic acid group received subcutaneous injection of 200μg/L bFGF and intraperitoneal injection of 10 mg/kg valproic acid.The wound healing rate of rats was detected at 7 and 14 days of administration.TUNEL was used to detect the apoptosis of cells in wound tissue.Enzyme linked immunosorbent assay was used to detect the serum levels of malondialdehyde,superoxide dismutase,tumor necrosis factor-αand interleukin-10.Immunofluorescence detection was conducted to detect the phenotypic transformation of macrophages in wound tissue.Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen,platelet endothelial cell adhesion molecule-1(CD31)and vascular endothelial growth factor in wound tissue.Western blot was used to detect the expression

关 键 词：碱性成纤维细胞生长因子 全层皮肤缺损 创面 巨噬细胞表型转换 肉芽再生 NOTCH1 JAGGED1 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R751