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Differential expression of histamine receptors in the bladder wall tissues of patients with bladder pain syndrome/interstitial cystitis – significance in the responsiveness to antihistamine treatment and disease symptoms
BMC Urology ( IF 1.7 ) Pub Date : 2019-11-12 , DOI: 10.1186/s12894-019-0548-3
Hui Shan , Er-Wei Zhang , Peng Zhang , Xiao-Dong Zhang , Ning Zhang , Peng Du , Yong Yang

Activation of mast cells plays an important role in the pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC). Histamine, a mast cell-derived mediators, induced inflammation and hypersensitivity of the bladder. The present study investigated the expressions of histamine receptors in the bladder wall tissues of patients with BPS/IC, and its association with the effectiveness of antihistamine therapy and disease symptoms. Bladder tissues were collected from 69 BPS/IC patients and 10 control female patients. The expression of H3R in BPS/IC was further examined in an independent cohort of 10 female patients with BPS/IC and another 10 age-matched female patients. Immunohistochemistry, Western blotting, and quantitative RT-PCR were performed to quantify the expressions of histamine receptors. Statistical analyses of the correlation of histamine receptor expression with antihistamine therapy outcome and severity of disease symptoms were also performed. The expression of four histamine receptors was significantly elevated in BPS/IC (H1R, P < 0.001; H2R, P = 0.031; H3R, P = 0.008; H4R, P = 0.048). Western blotting revealed that H3R were significantly reduced in the patients, whereas the mRNA levels of H3R were significantly increased. The patients were further divided into antihistamine responders (n = 38) and nonresponders (n = 22). No significant correlation was found in the expression of histamine receptors between responder and nonresponder groups. However, significant correlations between OLS and H1R (P = 0.003) and H3R (P = 0.045) were found. The present study showed that expression of all the 4 histamine receptors were elevated in BPS/IC. There were no statistical significant correlations between the expression levels of the four different histamine receptors and the treatment outcome of antihistamine therapy (amtitriptyline or cimetidine).

中文翻译:

组胺受体在膀胱疼痛综合征/间质性膀胱炎患者膀胱壁组织中的差异表达-在抗组胺药治疗反应和疾病症状中的意义

肥大细胞的激活在膀胱疼痛综合征/间质性膀胱炎(BPS / IC)的发病机理中起着重要作用。组胺是肥大细胞的介质,可引起膀胱炎症和超敏反应。本研究调查了BPS / IC患者膀胱壁组织中组胺受体的表达及其与抗组胺疗法的有效性和疾病症状的关系。从69名BPS / IC患者和10名对照女性患者中收集膀胱组织。在一个独立的队列中,对10名BPS / IC女性患者和另外10名年龄匹配的女性患者,进一步检查了H3R在BPS / IC中的表达。进行了免疫组织化学,Western印迹和定量RT-PCR来定量组胺受体的表达。还对组胺受体表达与抗组胺药治疗结果和疾病症状严重程度之间的相关性进行了统计分析。BPS / IC中四种组胺受体的表达显着升高(H1R,P <0.001; H2R,P = 0.031; H3R,P = 0.008; H4R,P = 0.048)。Western印迹显示,患者中H3R显着降低,而H3R的mRNA水平显着升高。患者进一步分为抗组胺药应答者(n = 38)和无应答药(n = 22)。在应答者和非应答者组之间的组胺受体表达中没有发现显着相关性。但是,发现OLS与H1R(P = 0.003)和H3R(P = 0.045)之间存在显着相关性。本研究表明,在BPS / IC中,所有4种组胺受体的表达均升高。四种不同组胺受体的表达水平与抗组胺药(阿米替林或西咪替丁)的治疗结果之间无统计学意义的相关性。
更新日期:2019-11-12
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