神经肽P物质通过调控表皮干细胞非对称增殖促进小鼠创伤愈合  

Neuropeptide Substance P Promotes Mice Wound Healing by Regulating Asymmetric Self⁃renewal of Skin Epidermal Stem Cells

作　　者：肖彤 夏育民[1] 肖生祥[1] XIAO Tong;XIA Yumin;XIAO Shengxiang(Department of Dermatology,The Second Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710004,China)

机构地区：[1]西安交通大学第二附属医院皮肤科,陕西西安710004

出　　处：《中国皮肤性病学杂志》2024年第2期147-152,共6页The Chinese Journal of Dermatovenereology

基　　金：陕西省遗传与感染性皮肤病临床研究中心项目(2016LCZX-03)。

摘　　要：目的探讨神经肽P物质(substance P)对小鼠皮肤创伤愈合的作用及其中表皮干细胞参与的机制。方法将野生型成年小鼠随机分为4组,分别为对照组(Control)、辣椒素处理组(Cap组)、P物质处理组(SP组)和辣椒素+P物质处理组(Cap+SP组),并进一步将4组小鼠分为创伤组与非创伤组。对创伤组小鼠进行直径为6 mm的创伤处理,每3 d拍照记录伤口愈合情况直至伤口愈合,于创伤后第4天取部分小鼠伤口周围皮肤提取表皮角质形成细胞进行免疫荧光染色以判断细胞增殖方式。非创伤组处理后取皮肤组织进行HE染色,对表皮进行表皮厚度和基底层细胞密度等指标的测定。结果与对照组相比,皮下注射P物质可加快皮肤创伤愈合(P=0.0561)、显著增加表皮干细胞非对称增殖(P=0.0003)及表皮厚度(P<0.0001);与Cap组相比,Cap+SP组中P物质的加入可逆转辣椒素导致的创伤愈合延缓(P<0.0001)、表皮干细胞非对称自我更新显著减少(P=0.019)、表皮厚度减少(P=0.0136)及基底层细胞密度减少(P<0.0001)的现象。结论神经肽P物质可有效促进皮肤创伤愈合,促进表皮复层化,其作用机制与基底层表皮干细胞非对称增殖的增加有关。Objective To explore the effect of neuropeptide,substance P on skin wound healing in mice and the mechanism of skin stem cells.Methods Group adult wild⁃type mice into control,capsaicin treated,substance P treated and capsaicin+substance P treated.Further divide these 4 groups of mice into wounded and non⁃wounded sub⁃groups.Perform biopsy punch wounds of 6 mm in diameter in wounded mice,and take pictures of the wounds every 3 days until healed.Isolate keratinocytes from peripheral of wounds on day 4 and perform immunofluorences to define different types of division.Perform HE staining in non⁃wounded mice to measure thickness of epidermis and basal cell density.Results Compared to control group,subcutaneous injection of substance P promotes skin wound healing in mice(P<0.0561),where skin stem cells undergo significantly more asymmetric self⁃renewal(P=0.0003)resulting in significantly increased epidermal thickness(P<0.0001).Substance P significantly rescues wound healing delay induced by capsaicin(P<0.0001),as well as the decrease in asymmetric self⁃renewal of stem cells(P=0.019),thinning of epidermis and density of basal cells(P=0.0136 and P<0.0001).Conclusion Substance P promotes skin wound healing by increasing asymmetric self⁃renewal of epidermal stem cells and promotes skin stratification.

关 键 词：成体干细胞 细胞自我更新 非对称性细胞分裂 创伤愈合 P物质 感觉缺失 

分 类 号：R751[医药卫生—皮肤病学与性病学]