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低亲和力神经生长因子受体p75在经典膀胱外翻中的表达

Expression of Low Affinity Nerve Growth Factor Receptor p75 in Classic Bladder Exstrophy.

作者信息

Promm Martin, Otto Wolfgang, Weber Florian, Götz Stefanie, Burger Maximilian, Müller Karolina, Rubenwolf Peter, Neuhuber Winfried, Roesch Wolfgang H

机构信息

Department of Pediatric Urology, Clinic St. Hedwig, University of Regensburg, Regensburg, Germany.

Department of Urology, Caritas-St. Josef Medical Center, University of Regensburg, Regensburg, Germany.

出版信息

Front Pediatr. 2021 Feb 22;9:634343. doi: 10.3389/fped.2021.634343. eCollection 2021.

Abstract

Successful primary closure of classic bladder exstrophy (BE) is crucial for development of bladder capacity and voided continence. It is universally agreed that an intensive pain management including the use of caudal epidural anesthesia is an essential cornerstone for the outcome of this complex surgery. Whether and to what extent pain is caused by structural or functional changes is not yet known. The nerve growth factor (NGF) is regarded as a marker for pain in different bladder disorders. This prospective study investigated the role of histological alterations and NGF in patients with BE including 34 patients with BE and 6 patients with congenital vesicoureterorenal reflux (VUR) who served as controls. Between January 2015 and April 2020 transmural bladder biopsies were taken from the posterior bladder wall during delayed primary bladder closure. The samples were stained for histological evaluation and subjected to immunohistochemistry to analyze NGFR p75. Differences in histological alterations were examined with Fisher's exact test, and Mann-Whitney-U-test was used to compare the NGFR p75 staining intensity between patients with BE and controls. Patients with BE showed significantly more often acute inflammation ( < 0.001), squamous metaplasia ( = 0.002), and cystitis glandularis ( = 0.005) as well as NGFR p75 in the urothelium ( = 0.003) than patients with VUR. A limitation of this study is the small number of participants due to the rare disease entity. Similar to other painful bladder disorders, pain transmission in BE after intitial closure may in part be facilitated by elevated NGF signaling through its receptor.

摘要

经典型膀胱外翻(BE)的一期成功闭合对于膀胱容量的发育和排尿自控至关重要。人们普遍认为,包括使用骶管硬膜外麻醉在内的强化疼痛管理是这一复杂手术成功的关键基石。疼痛是由结构改变还是功能改变引起,以及在何种程度上引起疼痛,目前尚不清楚。神经生长因子(NGF)被认为是不同膀胱疾病疼痛的标志物。这项前瞻性研究调查了组织学改变和NGF在BE患者中的作用,研究对象包括34例BE患者和6例先天性膀胱输尿管肾反流(VUR)患者作为对照。2015年1月至2020年4月期间,在延迟一期膀胱闭合时,从膀胱后壁取透壁膀胱活检组织。对样本进行染色以进行组织学评估,并进行免疫组织化学分析NGFR p75。组织学改变的差异采用Fisher精确检验,Mann-Whitney-U检验用于比较BE患者和对照组之间NGFR p75染色强度。与VUR患者相比,BE患者急性炎症(<0.001)、鳞状化生(=0.002)、腺性膀胱炎(=0.005)以及尿路上皮中NGFR p75(=0.003)的出现频率明显更高。由于该疾病实体罕见,本研究的一个局限性是参与者数量较少。与其他疼痛性膀胱疾病类似,初次闭合后BE中的疼痛传递可能部分是由NGF通过其受体的信号升高所促进的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3583/7937696/92f8a4df5b5a/fped-09-634343-g0001.jpg

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