Sci. Transl. Med.：雌激素可在绝经后妇女中抵御UTIs

据一项新的研究报告，在绝经后妇女中，雌激素可帮助保护其尿路免受感染。

这些发现可帮助解释为什么雌激素补充剂可在绝经后妇女中抵御感染复发。尿路感染或UTIs是妇女看医生的最常见原因之一——有多达60%的妇女至少会发生一次UTI，有25%的妇女有过反复的尿路感染。

Petra Lüthje及其同事如今显示，雌激素可增加身体自制的被称作抗菌肽的抗生素的产生。研究人员给一组绝经后妇女为期2周的雌激素补充剂并随后对这些实验参与者的尿液和膀胱内衬细胞进行了分析。他们发现，雌激素会作用于基因表达以帮助激活在膀胱中的某些抗菌肽的产生。该激素还会通过将膀胱内衬细胞之间的间隙粘合在一起而在结构上加强尿路组织，使得细菌更难通过膀胱内衬细胞而进入膀胱壁的较深层组织。在没有雌激素时，细菌较易“藏匿”在较深层的组织内，直到它们最终促发新的感染。尿液样本显示了细胞粘合的迹象以及抗菌肽产生的增加。研究人员同时发现，在绝经后妇女中雌激素增加了进入膀胱组织表面细胞的细菌量。

现在还不完全清楚这些结果对年轻或绝经前妇女中的UTI预防意味着什么，但它们可帮助解释为什么激素的局部治疗对某些绝经后妇女有好处。一则相应的《焦点》文章对这些发现进行了讨论

Estrogen Supports Urothelial Defense Mechanisms
Abstract
Epidemiological data imply a role of estrogen in the pathogenesis of urinary tract infections (UTIs), although the underlying mechanisms are not well understood. However, it is thought that estrogen supplementation after menopause decreases the risk of recurrent infections. We sought to investigate the influence of estrogen on host-pathogen interactions and the consequences for UTI pathogenesis. We analyzed urothelial cells from menstruating and postmenopausal women before and after a 2-week period of estrogen supplementation, and also studied the influence of estradiol during Escherichia coli UTI in a mouse infection model. Important findings were confirmed in two human urothelial cell lines. We identified two epithelial defense mechanisms modulated by estrogen. Estrogen induced the expression of antimicrobial peptides, thereby enhancing the antimicrobial capacity of the urothelium and restricting bacterial multiplication. In addition, estrogen promoted the expression and redistribution of cell-cell contact–associated proteins, thereby strengthening the epithelial integrity and preventing excessive loss of superficial cells during infection. These two effects together may prevent bacteria from reaching deeper layers of the urinary tract epithelium and developing reservoirs that can serve as a source for recurrent infections. Thus, this study presents some underlying mechanisms for the beneficial effect of estradiol after menopause and supports the application of estrogen in postmenopausal women suffering from recurrent UTI.