PDF(Pubmed)
Abstract：
Transurethral resection of the prostate, or other methods to decrease outlet resistance usually leads to relief of symptoms in patients with bladder outlet obstruction (BOO). If symptoms of underactivity persist after normalization of outflow conditions, treatment options are limited. In this review, we hypothesize, based on results from basic research, what might become treatment options for such patients in the future. The primary local treatment will still aim at reducing outlet obstruction. We speculate that local secondary treatment in the future might include transplantation of stem cells or mature bladder ganglion cells into the bladder wall. There has been some success in transplanting ganglion cells into the rat bladder. The ganglion cells will sprout into the surrounding tissue but functional connections between the axons of the transplanted neurons, and the detrusor smooth muscle have so far not been demonstrated. Neurotrophins or neurotrimin might be injected into the bladder wall to increase the sprouting of existing or transplanted neurons. Stem cell transplantation has been performed and improves detrusor function, but it has so far, been difficult to demonstrate transplanted stem cells. BOO, persisting detrusor underactivity, and decreased nerve density are often combined with inflammatory activity of the lower urinary tract. NLR family pyrin domain containing 3 (NLRP3) and its messenger RNA (mRNA) as well as cyclooxygenase-2 (Cox-2) mRNA are increased in obstructed bladders. Systemic treatment with the NLRP3 inhibitor glyburide normalized nerve density in rat bladder, and, to some extent, bladder function. It is unclear whether Cox-2 is involved in the decreased nerve density following obstruction, but Cox-2 mRNA increases 5-fold in obstructed bladder. Future therapy against bladder underactivity remaining following relief of obstruction includes either systemic treatment, perhaps by anti-inflammatory drugs, or local treatment by injection of stem cells, mature ganglion cells, and/or neurotrophins or neurotrimin into the bladder wall.
摘要：
经尿道前列腺切除术,或其他降低出口阻力的方法通常会导致膀胱出口梗阻（BOO）患者症状的缓解。如果在流出状况正常化后活动不足的症状持续存在，治疗方案有限。在这次审查中,我们假设，根据基础研究的结果，将来可能会成为此类患者的治疗选择。主要的局部治疗仍旨在减少出口阻塞。我们推测，未来的局部二次治疗可能包括将干细胞或成熟的膀胱神经节细胞移植到膀胱壁中。在将神经节细胞移植到大鼠膀胱中已经取得了一些成功。神经节细胞将发芽进入周围组织，但移植神经元轴突之间的功能连接，到目前为止，逼尿肌平滑肌还没有被证实。可以将神经营养蛋白或神经蛋白注射到膀胱壁中以增加现有或移植的神经元的发芽。干细胞移植已经进行，并改善逼尿肌功能，但到目前为止，很难证明移植的干细胞。BOO,持续的逼尿肌活动不足，和神经密度降低通常与下尿路的炎症活动相结合。在阻塞的膀胱中，含有NLR家族pyrin结构域3（NLRP3）及其信使RNA（mRNA）以及环氧合酶2（Cox-2）mRNA增加。NLRP3抑制剂格列本脲全身治疗大鼠膀胱神经密度正常化，and,在某种程度上,膀胱功能。目前尚不清楚Cox-2是否与梗阻后的神经密度降低有关，但Cox-2mRNA在阻塞膀胱中增加5倍。未来治疗膀胱活动不足仍在缓解梗阻包括全身治疗，也许是抗炎药，或者通过注射干细胞进行局部治疗，成熟的神经节细胞，和/或神经营养蛋白或神经蛋白进入膀胱壁。
