已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Inhibition of Notch signaling pathway reduces angiogenesis in hypertrophic scar.

增生性瘢痕 Notch信号通路 血管生成 医学 生理盐水 伤口愈合 新生血管 内科学 病理 内分泌学 解剖 外科 受体
作者
Songlian Li,Hongqiao Fan,Lifang Liu,Jie Ling,Yuwei Wu
出处
期刊:PubMed 卷期号:46 (11): 1195-1202
标识
DOI:10.11817/j.issn.1672-7347.2021.210234
摘要

Hypertrophic scar (HS) is the most common pathological scar in clinical practice. During its formation, angiogenesis-related factors show dynamic expression. Modern studies have found that Notch signaling pathway has an extremely important role in maintaining the construction and remodeling of vascular endothelial cells and vascular network. The correlation between Notch signaling pathway and angiogenesis in hypertrophic scar has been rarely reported. This study aims to investigate correlation between Notch signaling pathway and the expression of angiogenic factors in a proliferative scar model.A total of 81 Sprague Dawley rats (SPF grade) were randomly assigned into a blank control group, a model group, and a blocker group. In the blocker group, a 2 cm diameter circular scald head was placed on the back of the rats for 10 s at 75 ℃ by using a constant temperature and pressure electrothermal scalding apparatus to form a rat deep II° burn model, and a hyperplastic scar model rat was obtained after natural healing of the wound skin (21 to 23 day epithelialization). A syringe was used to inject a needle from the normal skin around the scar at the 1st, 3rd, 5th, 7th, and 14th days after modeling. The γ-secretase inhibitor was injected locally at 2 mg/kg in a dilution of 0.1 mL at the base of the scar. The rats in the model group was injected with the same amount of saline after modeling; the rats in the blank control group was injected with the same amount of saline. Nine rats in each group was randomly killed by air embolization at the 21st, 28th, and 35th days, respectively. The protein expressions of collagen type I (COL-I) and collagen type III (COL-III) were detected by immunohistochemistry. The protein expressions of vascular endothelial growth factor (VEGF), angiopoietin 1 (Ang1), transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase-2 (MMP-2) were detected by Western blotting.Immunohistochemical results showed that, at the 21st,28th, and 35th days, the protein expressions of COL-I and COL-III in the model group were up-regulated compared with the blank control group (all P<0.05) and the protein expressions of COL-I and COL-III in the blocker group were decreased compared with the model group (all P<0.05). Western blotting showed that, at the 21st, 28th, and 35th days, the protein expressions of VEGF, Ang1, TGF-β1, and MMP-2 in the model group were significantly higher than those in the blank control group (all P<0.05). Except for the 21st day, the protein expressions of VEGF, Ang1, TGF-β1, and MMP-2 in the blocker group were lower than those in the model group at the 28th and 35th days (all P<0.05).In the Sprague Dawley rat proliferative scar model, inhibition of Notch signaling pathway could attenuate the expressions of COL-I and COL-III, reduce traumatic scar proliferation, down-regulate the expressions of VEGF, Ang1, TGF-β1, and MMP-2, and inhibit angiogenesis. The expressions of angiogenesis-related factors appeare to be up-regulated during the formation of proliferative scar. When the Notch signaling pathway is inhibited, the up-regulated angiogenic factors show a decreasing trend and the proliferative scar is alleviated, which suggests that Notch signaling pathway may affect the formation of hyperplastic scar by regulating the expression of angiogenic factors.目的: 增生性瘢痕是临床上最常见的病理性瘢痕,在其形成过程中,血管生成相关因子呈现出动态表达。现代研究发现Notch信号通路对于维持血管内皮细胞和血管网的构建与重塑有着极其重要的作用,而Notch信号通路与血管生成的相关性在增生性瘢痕中的研究鲜有报道。本研究旨在探讨增生性瘢痕模型中Notch信号通路与血管生成因子表达的相关性。方法: 将81只Sprague Dawley大鼠(SPF级)随机分成空白对照组、模型组和阻滞剂组。其中阻滞剂组采用恒温恒压电热烫伤仪,在75 ℃条件下,将一个直径为2 cm的圆形烫伤头置于大鼠背部10 s,造成大鼠深II°烧伤,待烧伤皮肤自然愈合(21~23 d上皮化)后得到增生性瘢痕模型大鼠,在造模后第1、3、5、7和14天5个时间点用注射器从瘢痕周围正常皮肤进针,在瘢痕基底局部按2 mg/kg注射0.1 mL γ-分泌酶阻滞剂的稀释液。模型组在造模后同法注射等量生理盐水;空白对照组不造模,用同法注射等量生理盐水。每组分别在第21、28、35天3个时间点随机选取9只大鼠采用空气栓塞法处死。采用免疫组织化学法检测I型胶原蛋白(collagen type I,COL-I)、III型胶原蛋白(collagen type III,COL-III)的蛋白质表达;采用蛋白质印迹法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管生成素1(angiopoietin 1,Ang1)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)的蛋白质表达。结果: 免疫组织化学结果显示:在第21、28、35天3个时间点,与空白对照组比较,模型组COL-I、COL-III的蛋白质表达上调(均P<0.05);与模型组相比,阻滞剂组COL-I、COL-III的蛋白质表达下降(均P<0.05)。蛋白质印迹法结果显示:在第21、28、35天3个时间点,与空白对照组相比,模型组VEGF、Ang1、TGF-β1、MMP-2的蛋白质表达量均显著升高(均P<0.05);除第21天外,在第28、35天阻滞剂组VEGF、Ang1、TGF-β1及MMP-2的蛋白质表达量低于模型组(均P<0.05)。结论: 在Sprague Dawley大鼠增生性瘢痕模型中,抑制Notch信号通路可以减弱COL-I、COL-III的表达,减轻创面瘢痕增生,下调VEGF、Ang1、TGF-β1、MMP-2的表达,抑制血管新生。可见在增生性瘢痕的形成过程中,血管生成相关因子的表达出现上调;当抑制Notch信号通路后,上调的血管生成因子出现下降趋势,增生性瘢痕的情况也得到缓解。说明Notch信号通路可能通过调控血管生成因子的表达来影响增生性瘢痕的形成。.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
YDX关闭了YDX文献求助
1秒前
永远少年完成签到,获得积分10
2秒前
大模型应助Djnsbj采纳,获得10
2秒前
量子星尘发布了新的文献求助100
2秒前
一只熊完成签到 ,获得积分10
3秒前
Xx完成签到,获得积分10
5秒前
木子李完成签到,获得积分20
5秒前
6秒前
JamesPei应助整齐海秋采纳,获得10
7秒前
12秒前
WillGUO发布了新的文献求助10
13秒前
14秒前
整齐海秋完成签到,获得积分10
14秒前
隐形曼青应助小何HUHU采纳,获得10
15秒前
JAYZHANG完成签到,获得积分10
16秒前
雅典的宠儿完成签到 ,获得积分10
17秒前
Felicity完成签到 ,获得积分10
17秒前
17秒前
整齐海秋发布了新的文献求助10
20秒前
年少丶完成签到,获得积分10
20秒前
guozizi发布了新的文献求助30
24秒前
25秒前
芯之痕发布了新的文献求助10
26秒前
阿鑫完成签到 ,获得积分10
27秒前
客念完成签到 ,获得积分10
29秒前
温柔豁完成签到,获得积分10
31秒前
爱上学的小金完成签到 ,获得积分10
34秒前
迷人的天抒完成签到,获得积分10
35秒前
123123完成签到 ,获得积分10
37秒前
自然秋柳完成签到 ,获得积分10
38秒前
小蘑菇应助niu采纳,获得10
41秒前
柏小霜完成签到 ,获得积分0
41秒前
42秒前
大模型应助周雨昕采纳,获得10
42秒前
酷酷问夏完成签到 ,获得积分10
42秒前
刘闹闹完成签到 ,获得积分10
43秒前
44秒前
九九完成签到 ,获得积分10
45秒前
李治稳发布了新的文献求助10
45秒前
46秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3976583
求助须知:如何正确求助?哪些是违规求助? 3520659
关于积分的说明 11204399
捐赠科研通 3257298
什么是DOI,文献DOI怎么找? 1798683
邀请新用户注册赠送积分活动 877842
科研通“疑难数据库(出版商)”最低求助积分说明 806595