Herpud1在盆底肌萎缩模型中的表达研究  

Expression of Herpud1 in pelvic floor muscle atrophy model

作　　者：肖雅 洪莉[1] 闵洁[1] 汤剑明[1] 李素廷 陈茂 黄筱雨 Xiao Ya;Hong Li;Min Jie;Tang Jianming;Li Suting;Chen Mao;Huang Xiaoyu(Department of Obstetrics and Gynecology,People's Hospital of Wuhan University,Wuhan Hubei 430060,P.R.China)

机构地区：[1]武汉大学人民医院妇产科,湖北武汉430060

出　　处：《中国计划生育和妇产科》2022年第9期31-35,共5页Chinese Journal of Family Planning & Gynecotokology

基　　金：国家自然科学基金资助项目(项目编号:81971364);中央高校基本科研业务费专项资金资助(项目编号:2042022kf1107);国家重点研发计划资助(项目编号:2018YFC2002204,2021YFC2701302)。

摘　　要：目的探讨内质网膜蛋白Herpud1在盆底肌萎缩模型中的表达与作用。方法分别各取10只4月龄未生产过的野生型C57BL/6J小鼠(WT组)和盆底肌萎缩模型基因小鼠(T型钙离子通道编码基因CACNA1H敲除小鼠:Cacna1h-/-mice/TH-null组),异氟烷麻醉小鼠后,电生理记录仪对小鼠进行尿动力学指标的检测;处死小鼠后取盆底肌行免疫组化染色和Western-blot实验,分析Herpud1蛋白和mRNA水平的表达变化。选择鼠源C2C12成肌细胞分化4d形成肌管后,予以T型钙离子通道抑制剂NNC55-0396水合物(NNC)处理24h和48h,构建肌管萎缩细胞模型,Western-blot法检测Herpud1蛋白表达。结果小鼠尿动力学检测结果显示,与WT组小鼠相比,TH-null组小鼠膀胱漏尿点压(bladder leak point pressures,BLPP)值[(46.54±1.102)cmH_(2)O vs(31.55±2.177)cmH_(2)O]、最大膀胱容量值(0.1145±0.003023 vs 0.0691±0.004423)均显著降低,差异有统计学意义(P<0.0001);免疫组化染色、Western-blot检测结果均显示TH-null组小鼠盆底肌中Herpud1表达下降。C2C12分化肌管萎缩模型显示NNC处理以时间依赖的方式降低了Herpud1蛋白的表达水平。结论①Cacna1h-/-基因小鼠盆底肌萎缩模型中存在尿动力学指标的异常,说明盆底肌萎缩与压力性尿失禁(stress urinary incontinence,SUI)等盆底功能障碍病症发生相关;②Cacna1h-/-基因小鼠盆底肌萎缩模型和肌管细胞萎缩模型中Herpud1表达水平均下降,Herpud1在盆底肌萎缩过程中可能具有重要调节作用。Objective To investigate the expression and function of endoplasmic reticulum protein Herpud1 in pelvic floor muscle atrophy model.Methods Seleacted ten 4-month-old unborn wild-type C57 BL/6 J mice(WT group) and pelvic floor muscle atrophy model gene mice(T-type calcium channel encoding gene CACNA1 H knockout mice: Cacna1 h-/-mice/TH-null group),after isoflurane anesthetized the mice, the electrophysiological recorder was used to detect the urodynamic indexes of the mice;after the mice were sacrificed, the pelvic floor muscles were collected for immunohistochemical staining and Western-blot experiments, the expression changes of Herpud1 protein and mRNA levels were analyzed.Selected murine C2 C12 myoblasts differentiated for 4 days to form myotubes, and then treated with T-type calcium channel inhibitor NNC 55-0396 hydrate(NNC) for 24 h and 48 h to build a myotube atrophy cell model.Herpud1 protein expression was detected by Western-blot method.Results The results of mouse urodynamic testing showed that compared with mice in WT group, bladder leak point pressures(BLPP) values of mice in TH-null group were [(46.54 ± 1.102)cmHO vs(31.55±2.177)cmHO] and maximum bladder capacity(MBC) values(0.1145±0.003023 vs 0.0691±0.004423) were significantly decreased, and the difference was statistically significant(P<0.0001);immunohistochemical staining and Western-blot test results showed that the Herpud1 expression was decreased in TH-null group rat pelvic floor muscles.The C2 C12 differentiated myotube atrophy model showed that NNC treatment reduced the expression level of Herpud1 protein in a time-dependent manner.Conclusion(1) There are abnormal urodynamic indexes in the Cacna1 h-/-gene mouse model of pelvic floor muscle atrophy, indicating that pelvic floor muscle atrophy is related to the occurrence of PFD diseases such as stress urinary incontinence(SUI);(2) The expression level of Herpud1 decreased in both pelvic floor muscle atrophy model and myotube atrophy model in Cacna1 h-/-gene mice, and Herpud1 may have an im

关 键 词：Herpud1 盆底肌萎缩 内质网 阴道分娩 

分 类 号：R543.1[医药卫生—心血管疾病] R711.4[医药卫生—内科学]