International Federation for Family Health, Chapel Hill, NC, USA.
J Reprod Immunol. 2013 Apr;97(2):159-66. doi: 10.1016/j.jri.2012.12.003. Epub 2013 Feb 28.
Quinacrine has been widely used in treatment of parasitic diseases such as malaria and giardiasis, and in the treatment of autoimmune diseases. Quinacrine has also been used as an effective substitute for surgical contraception by causing occlusion of the fallopian tube. This minimally invasive treatment protocol involves intrauterine insertion of the drug in the form of pellets and has been studied in humans in a number of countries, including the United States. Despite its development in the 1970s, the cellular and molecular events induced by quinacrine in the human fallopian tube have not been described. Here we describe a plausible mechanism for quinacrine action in the fallopian tube. This is manifested as an acute pro-inflammatory response in the uterus and fallopian tube, characterized by loss of epithelial cell adhesion. This response relies on properties of gated channels found on the surface of epithelial cells in the reproductive tract. While the uterus returns to normal, the inflammatory response affects the uterotubal junction and transmural segment of the human fallopian tube, and initiates formation of mature collagen in the lumen of the fallopian tube, resulting in its permanent occlusion. The response within the fallopian tube appears similar to the protective mechanisms that have evolved in women to minimize the likelihood of systemic infection from Neisseria gonorrhoeae, and to some extent from Chlamydia trachomatis. This review could assist in development of experimental models used in investigating the mechanisms of fibrotic responses in humans as well as development of techniques for permanent non-surgical female contraception.
盐酸奎宁已被广泛用于治疗疟疾和贾第虫病等寄生虫病，以及治疗自身免疫性疾病。盐酸奎宁也被用作一种有效的输卵管绝育手术替代方法，通过阻塞输卵管来实现。这种微创治疗方案涉及将药物以丸剂形式宫内插入，已经在包括美国在内的多个国家的人群中进行了研究。尽管它是在 20 世纪 70 年代开发的，但盐酸奎宁在人输卵管中诱导的细胞和分子事件尚未被描述。在这里，我们描述了盐酸奎宁在输卵管中作用的一种可能机制。这表现为子宫和输卵管的急性促炎反应，其特征是上皮细胞黏附丧失。这种反应依赖于生殖道上皮细胞表面上发现的门控通道的特性。虽然子宫恢复正常，但炎症反应会影响输卵管与子宫的连接和输卵管的壁内段，并在输卵管腔内引发成熟胶原的形成，导致其永久性阻塞。输卵管内的反应类似于女性为了最大限度地减少淋病奈瑟菌（Neisseria gonorrhoeae）和在某种程度上沙眼衣原体（Chlamydia trachomatis）引起全身感染的可能性而进化出的保护机制。这篇综述可以帮助开发用于研究人类纤维反应机制的实验模型，以及开发用于永久性非手术女性避孕的技术。
