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良性前列腺增生中α1-肾上腺素能受体的亚型:个性化医疗的未来前景

Subtypes of alpha1-adrenoceptors in BPH: future prospects for personalized medicine.

作者信息

Kojima Yoshiyuki, Sasaki Shoichi, Hayashi Yutaro, Tsujimoto Gozoh, Kohri Kenjiro

机构信息

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

出版信息

Nat Clin Pract Urol. 2009 Jan;6(1):44-53. doi: 10.1038/ncpuro1276.

Abstract

The alpha(1)-adrenoceptors (alpha(1)-ARs) are involved in regulation of prostatic smooth muscle tone, and are a critical mediator of lower urinary tract symptoms and pathophysiology in benign prostatic hyperplasia (BPH). As a result, alpha(1)-AR antagonists are now used as first-line medical treatment for BPH. Three alpha(1)-AR subtypes (alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR) have been identified on the basis of results of pharmacological and molecular cloning studies; however, the precise physiological role of individual alpha(1)-AR subtypes remains elusive. The expression levels of alpha(1)-AR subtypes in the prostate differ between patients, and individual differences in the genetic background of patients with BPH might be associated with variation in responses to subtype-selective alpha(1)-AR antagonists. In addition, single nucleotide polymorphism and microarray-based gene expression profiling studies might provide an opportunity to identify markers that predict clinical response and therapeutic tolerance to alpha(1)-AR antagonists. Further genomic studies will refine our knowledge of the functions of alpha(1)-AR subtypes, lead to new strategies for the clinical management of BPH and, perhaps, enable personalized treatment of BPH in the future.

摘要

α1肾上腺素能受体(α1-ARs)参与前列腺平滑肌张力的调节,是良性前列腺增生(BPH)患者下尿路症状及病理生理学的关键介质。因此,α1-AR拮抗剂目前被用作BPH的一线药物治疗。基于药理学和分子克隆研究结果,已鉴定出三种α1-AR亚型(α1a-AR、α1b-AR、α1d-AR);然而,各α1-AR亚型的确切生理作用仍不清楚。前列腺中α1-AR亚型的表达水平在患者之间存在差异,BPH患者遗传背景的个体差异可能与对亚型选择性α1-AR拮抗剂反应的差异有关。此外,单核苷酸多态性和基于微阵列的基因表达谱研究可能为识别预测α1-AR拮抗剂临床反应和治疗耐受性的标志物提供机会。进一步的基因组研究将完善我们对α1-AR亚型功能的认识,为BPH的临床管理带来新策略,并可能在未来实现BPH的个性化治疗。

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