Probucol improves erectile function by regulating endoplasmic reticulum stress in rats with streptozotocin-induced diabetes
Probucol improves erectile function by regulating endoplasmic reticulum stress in rats with streptozotocin-induced diabetes
复制标题
普罗布考通过调节链脲佐菌素诱导的糖尿病大鼠的内质网应激改善勃起功能
作者：
Ruan Zheng;Wang Haoran;Zhang Keqin;Xu Zhen;Zang Zhenjie;Fu Qiang
本研究旨在探讨普罗布考对链脲佐菌素诱导的糖尿病大鼠勃起功能障碍的影响及其机制。12周龄雄性SD大鼠30只，禁食12小时后，腹腔注射链脲佐菌素。将糖尿病大鼠随机分成两组，分别给予普罗布考0或500 mg/kg灌胃，连续12周。对照组腹腔注射生理盐水，每日灌胃生理盐水。采用体外压力评价勃起功能。用免疫组织化学和Western blotting检测蛋白质水平。免疫荧光染色检测α-SMA和vWF。普罗布考组治疗后勃起功能明显改善。DM组内质网应激相关蛋白的表达高于假手术组，普罗布考组内质网应激相关蛋白的表达明显减少。而α-SMA和vWF在DM组的表达水平低于假手术组，普罗布考可逆转这一现象。糖尿病组Bax、Caspase3高表达，Bcl2低表达，普罗布考组则相反。总之，普罗布考通过减少内皮功能障碍和抑制PERK/ATF4/CHOP通路改善STZ诱导的糖尿病大鼠的勃起功能。
This study was to explore the effect and mechanism of Probucol on STZ‐induced erectile dysfunction in diabetic rats. ThirtySDmale rats aged 12 weeks were given intraperitoneal injection of STZ after fasting for 12 hr. Diabetic rats were haphazardly partitioned under two assemblies and administered 0 or 500 mg/kg probucol by oral gavage to 12 weeks. Control group was intraperitoneally injected with physiological saline, and saline was administered by oral gavage daily. Intracorporeal pressure was used to evaluate erectile function. Levels of proteins were detected using immunohistochemistry and Western blotting. α‐SMA and vWF were detected using immunofluorescence staining. After treatment, erectile function in probucol group was significantly improved. Endoplasmic reticulum stress‐related proteins were expressed higher in DM group than in sham group, while expression of these proteins decreased significantly in probucol group. However, α‐SMA and vWF were expressed at lower levels in DM group than in sham group, and probucol treatment reversed this phenomenon. Finally, Bax and Caspase3 were expressed at higher levels and Bcl‐2 was expressed at lower levels in DM group, while the opposite result was obtained in probucol group. In conclusions, probucol improves erectile function by reducing endothelial dysfunction and inhibiting PERK/ATF4/CHOP pathway in STZ‐induced diabetic rats.