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普罗布考通过调节链脲佐菌素诱导的糖尿病大鼠内质网应激改善勃起功能。

Probucol improves erectile function by regulating endoplasmic reticulum stress in rats with streptozotocin-induced diabetes.

机构信息

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P.R. China.

Tai'an City Central Hospital, Tai'an, P.R. China.

出版信息

Andrologia. 2021 May;53(4):e13999. doi: 10.1111/and.13999. Epub 2021 Feb 10.

DOI:10.1111/and.13999
PMID:33565104
Abstract

This study was to explore the effect and mechanism of Probucol on STZ-induced erectile dysfunction in diabetic rats. Thirty SD male 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.

摘要

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作用及其机制。30 只 12 周龄雄性 SD 大鼠禁食 12 小时后腹腔注射 STZ。糖尿病大鼠随机分为两组,分别灌胃 0 或 500mg/kg 普罗布考 12 周。对照组腹腔注射生理盐水,每日灌胃生理盐水。采用体内压力评估勃起功能。采用免疫组化和 Western blot 检测蛋白水平。采用免疫荧光染色检测α-SMA 和 vWF。治疗后,普罗布考组勃起功能明显改善。DM 组内质网应激相关蛋白的表达高于 sham 组,而普罗布考组的表达明显降低。然而,DM 组的α-SMA 和 vWF 的表达水平低于 sham 组,普罗布考治疗逆转了这种现象。最后,DM 组的 Bax 和 Caspase3 表达水平较高,Bcl-2 表达水平较低,而普罗布考组则相反。结论:普罗布考通过减少内皮功能障碍和抑制 STZ 诱导的糖尿病大鼠 PERK/ATF4/CHOP 通路来改善勃起功能。

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