Notch3/DLL4信号通路对颈部淋巴水囊瘤后淋巴管发育的影响  

The effect of Notch3/DLL4 signal pathway on the lymphatic development after cystic hygroma

作　　者：王荣跃[1] 邱海凡[1] 戴芬 楼文文[2] 宫剑[2] 谢爱兰[1] WANG Rongyue;QIU Haifan;DAI Fen;LOU Wenwen;GONG Jian;XIE Ailan(Department of Obstetrics and Gynecology,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325027,China;Department of Laboratory Medicine,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325027,China)

机构地区：[1]温州医科大学附属第二医院妇产科,浙江温州325027 [2]温州医科大学附属第二医院检验医学科,浙江温州325027

出　　处：《温州医科大学学报》2024年第1期20-24,30,共6页Journal of Wenzhou Medical University

基　　金：浙江省医药卫生科技计划项目(2020KY641);温州市基础性科研项目(Y20210019);浙江省自然科学基金项目(LY19HO40006)。

摘　　要：目的:探究Notch3/DLL4信号通路对颈部淋巴水囊瘤(CH)后淋巴管成熟发育的影响。方法:选取C57BL/6小鼠和C57BL/6背景Notch3基因敲入小鼠,将两种小鼠分为正常组(对照组)和Notch3基因敲入组(突变组)。选取F2代小鼠处死,取小鼠颈部淋巴结分别进行HE染色、Masson染色、RT-qPCR、Western blot、免疫组化检测。结果:HE及Masson染色结果显示,与对照组比,突变组小鼠的淋巴结构被显著破坏,细胞纤维化严重。RT-qPCR结果显示,与对照组比,突变组小鼠淋巴结中DLL4、Hes1和VEGFR3 mRNA表达显著下降(P<0.05)。Western blot结果显示,与对照组比,突变组小鼠淋巴结中DLL4、Hes1和VEGFR3蛋白表达显著下降(P<0.05)。免疫组化结果显示,与对照组相比,突变组小鼠淋巴结中DLL4、Hes1、Ang2、VEGFA和VEGFR3染色较浅,蛋白表达水平下降(P<0.05)。结论:Notch3/DLL4信号通路能够调控小鼠颈部CH的形成,其机制可能与淋巴管发育有关。Objective:To investigate the effect of Notch3 signaling pathway on the maturation and development of fetal lymphatic vessels after cystic hygroma(CH).Methods:C57BL/6 mice and C57BL/6 background Notch3 gene knock-in mice were divided into a normal control group and a mutation group.Cervical lymph nodes were collected from F2 generation mice for HE staining,Masson staining,RT-qPCR,Western blot,and immunohistochemical analysis.Results:Compared with the control group.the results of HE and Masson staining showed that the cervical lymph nodes of the mutant mice were significantly disrupted and cellular fibrosis was severe;RT-qPCR results showed that the mRNA expression of DLL4,Hes1,and VEGFR3in lymphatic nodes of Notch3 mutant mice was significantly decreased,which had statistical difference(P<0.05);Western blot analysis showed that the expression of DLL4,Hes1,and VEGFR3 proteins in the lymphoid nodes of Notch3 mutant mice was remarkably decreased,indicating significant difference(P<0.05);immunohistochemical analysis showed that the expression of DLL4,Hes1,Ang2,VEGFA,and VEGFR3 in the lymphoid nodes of Notch3 mutant mice was decreased,with significant difference(P<0.05).Conclusion:Notch3 regulates cystic hygroma in mice,and its mechanism is likely to be through lymphatic vessel neogenesis.

关 键 词：NOTCH3 DLL4 信号通路 淋巴水囊瘤 淋巴管新生 小鼠 

分 类 号：R714.7[医药卫生—妇产科学]