Pang X, Cotreau-Bibbo M M, Sant G R, Theoharides T C
Department of Pharmacology, Tufts University School of Medicine, New England Medical Center Hospital, Boston, Massachusetts.
Br J Urol. 1995 Feb;75(2):154-61. doi: 10.1111/j.1464-410x.1995.tb07303.x.
To investigate the role of oestrogens in the pathophysiology of interstitial cystitis (IC), specifically with respect to activated bladder mast cells (MC), as well as urine concentrations of MC-derived histamine and methylhistamine, all of which are increased in patients with IC. This goal appeared important because IC is a bladder disorder which occurs almost exclusively in women, and is characterized by polyuria, nocturia and pelvic pain, which worsen perimenstrually.
Biopsies from six patients with IC and four control patients were analysed blindly for the presence of oestrogen receptors (OR) using both custom-made and commercially available antibodies against OR.
Bladder MC alone were shown to express high-affinity OR and there was a higher number of such cells present in patients with IC compared with controls. The identity of MC in the bladder was documented with immunohistochemistry for tryptase. OR were also identified in human MC (HMC-1), a MC line kept in culture. These steps were necessary because of the unique finding that only MC express OR, in spite of the inflammatory infiltrate present.
These findings may help to explain why IC occurs primarily in women, why IC and other associated symptoms tend to be worst at the midcycle, and may also suggest that prognostic usefulness of staining bladder biopsies for OR. These results are particularly interesting because oestradiol has been shown to augment MC histamine secretion in response to the neuropeptide, substance P, which may be released in certain neuroinflammatory disorders which have a high prevalence in women, such as IC and irritable bowel syndrome.
研究雌激素在间质性膀胱炎(IC)病理生理学中的作用,特别是关于活化的膀胱肥大细胞(MC),以及MC衍生的组胺和甲基组胺的尿液浓度,这些在IC患者中均升高。这一目标显得很重要,因为IC是一种几乎仅发生于女性的膀胱疾病,其特征为多尿、夜尿和盆腔疼痛,在月经周期中会加重。
使用针对雌激素受体(OR)的定制抗体和市售抗体,对6例IC患者和4例对照患者的活检组织进行OR存在情况的盲法分析。
仅膀胱MC显示表达高亲和力OR,与对照组相比,IC患者中存在的此类细胞数量更多。用抗胰蛋白酶的免疫组织化学方法证实了膀胱中MC的特性。在培养的MC系人MC(HMC - 1)中也鉴定出了OR。这些步骤是必要的,因为尽管存在炎性浸润,但只有MC表达OR这一独特发现。
这些发现可能有助于解释为什么IC主要发生在女性中,为什么IC及其他相关症状在月经周期中期往往最为严重,还可能提示对膀胱活检进行OR染色的预后价值。这些结果特别有趣,因为已表明雌二醇可增强MC对神经肽P物质的组胺分泌反应,P物质可能在某些女性中高发的神经炎症性疾病(如IC和肠易激综合征)中释放。