Cui Kai, Ruan Yajun, Wang Tao, Rao Ke, Chen Zhong, Wang Shaogang, Liu Jihong
Institute of Urology and Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Institute of Urology and Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Sex Med. 2017 Mar;14(3):323-335. doi: 10.1016/j.jsxm.2017.01.006. Epub 2017 Feb 2.
Erectile dysfunction (ED) in patients with diabetes mellitus (DM) seriously affects their quality of life. However, these patients show a poor effect rate for oral phosphodiesterase type 5 inhibitors. Thus, new treatment methods are urgently needed. Fingolimod hydrochloride (FTY720) was approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple sclerosis.
To investigate whether FTY720 supplementation could ameliorate ED induced by DM (DMED).
Forty male Sprague-Dawley rats (8 weeks old) were used for the experiment. Thirty-two had type 1 DM induced by streptozotocin and the other eight rats constituted the control group. Eight weeks later, the erectile function of rats was assessed with an apomorphine test. Only some rats with DMED were treated with FTY720 orally every day for 4 weeks; the other rats remained in the same condition for 4 weeks.
Metabolic parameters; erectile function; sphingosine-1-phosphate receptor 3 (S1P3), protein kinase B (Akt), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) signaling pathway; corporal fibrosis; apoptosis level; and Smad and non-Smad signaling pathways.
There were no significant differences in the initial body weights and fasting glucose concentrations among the three groups. Erectile function in the DMED group was significantly impaired compared with the control group and was partly, but significantly, improved in the DMED + FTY720 group. The DMED group showed inhibited activity of the S1P3-Akt-NO-cGMP signaling pathway, and the inhibition was partly reversed in the DMED + FTY720 group. The DMED group showed serious corporal fibrosis, higher apoptosis level, higher ratio of Bax to Bcl-2, and higher expressions of the Smad pathway (transforming growth factor-β1, Smad, and connective tissue growth factor) and the non-Smad pathway (transforming growth factor-β1, rho-associated protein kinase, LIM domain kinase 2, and cofilin). However, FTY720 supplementation partly increased the ratio of smooth muscle to collagen, decreased the ratio of Bax to Bcl-2, and inhibited activity of the Smad and non-Smad pathways.
FTY720 supplementation inhibited endothelial dysfunction and corporal fibrosis, ultimately leading to partial improvement of DMED in rats. This finding provides evidence for a potential treatment method for DMED. Cui K, Ruan Y, Wang T, et al. FTY720 Supplementation Partially Improves Erectile Dysfunction in Rats With Streptozotocin-Induced Type 1 Diabetes Through Inhibition of Endothelial Dysfunction and Corporal Fibrosis. J Sex Med 2017;14:323-335.
糖尿病（DM）患者的勃起功能障碍（ED）严重影响其生活质量。然而，这些患者口服5型磷酸二酯酶抑制剂的有效率较低。因此，迫切需要新的治疗方法。盐酸芬戈莫德（FTY720）于2010年被批准用于治疗复发缓解型多发性硬化症患者。
研究补充FTY720是否能改善糖尿病所致勃起功能障碍（DMED）。
选用40只8周龄雄性Sprague-Dawley大鼠进行实验。32只通过链脲佐菌素诱导患1型糖尿病，另外8只大鼠作为对照组。8周后，用阿扑吗啡试验评估大鼠的勃起功能。仅对部分DMED大鼠每天口服FTY720，持续4周；其他大鼠保持相同状态4周。
代谢参数；勃起功能；鞘氨醇-1-磷酸受体3（S1P3）、蛋白激酶B（Akt）、一氧化氮（NO）和环磷酸鸟苷（cGMP）信号通路；海绵体纤维化；凋亡水平；以及Smad和非Smad信号通路。
三组大鼠的初始体重和空腹血糖浓度无显著差异。与对照组相比，DMED组的勃起功能明显受损，而DMED + FTY720组的勃起功能有部分但显著的改善。DMED组的S1P3-Akt-NO-cGMP信号通路活性受到抑制，而在DMED + FTY720组中这种抑制作用得到部分逆转。DMED组表现出严重的海绵体纤维化、更高的凋亡水平、更高的Bax与Bcl-2比值，以及Smad通路（转化生长因子-β1、Smad和结缔组织生长因子）和非Smad通路（转化生长因子-β1、rho相关蛋白激酶、LIM结构域激酶2和丝切蛋白）的更高表达。然而，补充FTY720部分提高了平滑肌与胶原蛋白的比例，降低了Bax与Bcl-2的比值，并抑制了Smad和非Smad通路的活性。
补充FTY720可抑制内皮功能障碍和海绵体纤维化，最终使大鼠的DMED得到部分改善。这一发现为DMED的潜在治疗方法提供了证据。崔K，阮Y，王T等。补充FTY720通过抑制内皮功能障碍和海绵体纤维化部分改善链脲佐菌素诱导的1型糖尿病大鼠的勃起功能障碍。《性医学杂志》2017；14：323 - 335。
