Department of Urology and IBMC, Hospital de São João and Faculty of Medicine of Porto, Porto, Portugal.
Neurourol Urodyn. 2014 Jan;33(1):31-8. doi: 10.1002/nau.22445. Epub 2013 Jun 17.
Botulinum toxin type A (BoNT/A), one of the seven subtypes of Botulinum toxin, is commercially available naked or complexed to other proteins. Onabotulinum toxin type A is the most extensively studied BoNT/A brand. Dose equivalence studies between the different brands have never been carried out. BoNT/A is internalized by nerve fibers after binding synaptic vesicle proteins, and the final target of action is synaptosome-associated protein 25 kDa (SNAP-25), a membrane protein essential for synaptic vesicle fusion with the neuronal membrane.
The current literature about botulinum toxin mechanisms was reviewed to provide an up to date knowledge about the topic.
Immunoreactivity to cleaved SNAP-25, the end product of BoNT/A activity, has been identified in parasympathetic (pre- and postganglionic), sympathetic, and afferent fibers. A consistent decrease in the release of acetylcholine from parasympathetic, norepinephrine from sympathetic, and glutamate and neuropeptides from sensory neurons follows BoNT/A administration. Immunoreactivity to cleaved SNAP-25 was not identified in the urothelium or in myofibroblasts. Nevertheless, a decreased release of ATP and neurotrophins from the urothelial cells has been consistently observed after BoNT/A. The toxin does not cause apoptosis in the bladder. However, injection in rat and dog prostates was shown to induce apoptosis in acinar and stromal cells.
There is now robust information to support that the mechanism of action of BoNT/A in the bladder involves neurotransmitter release from nerve fibers and urothelial cells. Which neurotransmitter is more relevant is, however, unclear. Likewise, the long duration of effect, the importance of the volume of vehicle injected and the selection of specific injection sites, like the trigone, needs further evaluation.
肉毒毒素 A 型（BoNT/A）是肉毒毒素的七种亚型之一，可单独使用或与其他蛋白质结合使用。 肉毒毒素 A 是研究最广泛的 BoNT/A 品牌。不同品牌之间的剂量等效性研究从未进行过。BoNT/A 结合突触小泡蛋白后被神经纤维内化，最终作用靶点是突触相关蛋白 25kDa（SNAP-25），这是一种对于突触小泡与神经元膜融合至关重要的膜蛋白。
回顾了关于肉毒毒素机制的当前文献，以提供有关该主题的最新知识。
已在副交感神经（节前和节后）、交感神经和传入纤维中鉴定出对 BoNT/A 活性的裂解 SNAP-25 的免疫反应性。BoNT/A 给药后，副交感神经释放的乙酰胆碱、交感神经释放的去甲肾上腺素以及感觉神经元释放的谷氨酸和神经肽减少。裂解 SNAP-25 的免疫反应性未在尿路上皮或肌成纤维细胞中鉴定出来。然而，在 BoNT/A 后，始终观察到尿路上皮细胞中 ATP 和神经营养因子的释放减少。该毒素不会引起膀胱细胞凋亡。然而，在大鼠和狗前列腺中的注射显示出在腺泡和基质细胞中诱导细胞凋亡。
现在有强有力的信息支持 BoNT/A 在膀胱中的作用机制涉及神经纤维和尿路上皮细胞中神经递质的释放。然而，哪种神经递质更为重要尚不清楚。同样，作用时间长、注射载体的体积重要性以及选择特定的注射部位（如三角区）需要进一步评估。
