The near-infrared dye IR-61 restores erectile function in a streptozotocin-induced diabetes model via mitochondrial protection  

作　　者：Xiao-Feng Yue Chong-Xing Shen Jian-Wu Wang Lin-Yong Dai Qiang Fang Lei Long Yi Zhi Xue-Ru Li Ya-Wei Wang Gu-Fang Shen Zu-Juan Liu Chun-Meng Shi Wei-Bing Li 

机构地区：[1]Departm ent of Urology,The Third Affiliated Hospital of Chongqing Medical University(Gener Hospital),Chongqing 401120,China [2]lnstitute of Rocket Force Medicine,State Key Laboratory of Trauma,Burns and Combined Injury,Third Military Medical University,Chongqing 400038,China [3]Department of Ophthalmology,The Third Affiliated Hospital of Chongqing M edical University(Gener Hospital),Chongqing 401120,China

出　　处：《Asian Journal of Andrology》2021年第3期249-258,共10页亚洲男性学杂志（英文版）

基　　金：the National Key Research and Development Program(2016Y FC1000805);University Innovation Team Building Program of Chongqing(CXTDG201602020);Science and Technology Research Program of Chongqing Municipal Education Commission(KJQN202000433).

摘　　要：This study aimed to evaluate the therapeutic effect of IR-61,a novel mitochondrial heptamethine cyanine dye with antioxidant effects,on diabetes mellitus-induced erectile dysfunction(DMED).Eight-week-old male Sprague-Dawley rats were intraperitoneally injected with streptozotocin(STZ)to induce type 1 diabetes.Eight weeks after STZ injection,all rats were divided into three groups:the control group,DM group,and DM+IR-61 group.In the DM+IR-61 group,the rats were administered IR-61(1.6 mg kg-1)twice a week by intravenous injection.At week 13,erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure,and the penises were then harvested for fluorescent imaging,transmission electron microscopy,histological examinations,and Western blot analysis.Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection.IR-61 treatment significantly improved the maximal ICP of diabetic rats.Additionally,IR-61 ameliorated diabetes-induced inflammation,apoptosis,and phenotypic transition of corpus cavernosum smooth muscle cells(CCSMCs)in penile tissue.IR-61 also attenuated mitochondrial damage,reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuinl(SIRT1),sirtuin3(SIRT3),nuclear factor(erythroid-derived 2)-like 2(Nrf2),and heme oxygenase expression in penile tissue.In conclusion,IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs,which may be mediated by activation of the SIRT1,SIRT3,and Nrf2 pathways.

关 键 词：corpus cavernosum smooth muscle cells diabetes erectile dysfunction IR-61 MITOCHONDRIA 

分 类 号：R587.1[医药卫生—内分泌]