Akdeniz University, Medical Faculty, Department of Pharmacology, 07070, Antalya, Turkey.
Akdeniz University, Medical Faculty, Department of Pharmacology, 07070, Antalya, Turkey.
Peptides. 2018 Aug;106:1-8. doi: 10.1016/j.peptides.2018.05.005. Epub 2018 May 21.
The aim of this study was to investigate the effect of chronic exendin-4 (Ex-4) treatment on corpus cavernosum (CC) dysfunction in methylglyoxal (MGO) administered rats.
Male rats were divided into four groups as control, MGO (75 mg/kg/day in drinking water for 12 weeks), MGO + low-dose Ex-4 (0.1 μg/kg twice daily subcutaneously for 12 weeks concomitant with MGO), and MGO + high-dose Ex-4 (1 μg/kg twice daily subcutaneously for 12 weeks concomitant with MGO). Nitric oxide (NO)-mediated endothelium-dependent and neurogenic CC relaxations were evaluated by acetylcholine (ACh) and electrical field stimulation (EFS), respectively. Apoptosis was determined by TUNEL. Endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), NADPH oxidase subunit gp91phox (NOX2), and Rho kinase (ROCK2) expressions in CC were investigated by immunohistochemistry. Levels of the malondialdehyde (MDA) and advanced oxidation protein products (AOPP) were also measured.
In MGO administered rats, both endothelium-dependent and neurogenic CC relaxations were significantly impaired as compared to controls. Apoptotic cell death and levels of MDA and AOPP increased significantly in MGO administered rats. eNOS and p-eNOS expressions decreased significantly in MGO group, while gp91phox expressions increased significantly. The diminished relaxation in response to ACh or EFS as well as the changes in expression of proteins in MGO groups were significantly improved by exendin-4 treatment. TUNEL-positive cells, and levels of MDA and AOPP in MGO group rats were also significantly reduced by exendin-4.
Exendin-4 treatment improves NO-mediated CC relaxations in MGO administered rats probably by inhibiting NADPH oxidase.
本研究旨在探讨慢性 exendin-4（Ex-4）治疗对甲基乙二醛（MGO）给药大鼠海绵体（CC）功能障碍的影响。
雄性大鼠分为对照组、MGO 组（75mg/kg/天饮用水，共 12 周）、MGO+低剂量 Ex-4 组（0.1μg/kg/天皮下注射，共 12 周与 MGO 同时给药）和 MGO+高剂量 Ex-4 组（1μg/kg/天皮下注射，共 12 周与 MGO 同时给药）。通过乙酰胆碱（ACh）和电刺激（EFS）分别评估一氧化氮（NO）介导的内皮依赖性和神经源性 CC 松弛。通过 TUNEL 确定细胞凋亡。通过免疫组化检测 CC 中的内皮型一氧化氮合酶（eNOS）、磷酸化 eNOS（p-eNOS）、NADPH 氧化酶亚单位 gp91phox（NOX2）和 Rho 激酶（ROCK2）表达。还测量丙二醛（MDA）和高级氧化蛋白产物（AOPP）的水平。
与对照组相比，MGO 给药大鼠的内皮依赖性和神经源性 CC 松弛均明显受损。MGO 给药大鼠的凋亡细胞死亡以及 MDA 和 AOPP 的水平显著增加。eNOS 和 p-eNOS 的表达在 MGO 组显著降低，而 gp91phox 的表达显著增加。MGO 组对 ACh 或 EFS 的反应性松弛以及蛋白质表达的变化均通过 exendin-4 治疗得到显著改善。TUNEL 阳性细胞以及 MGO 组大鼠 MDA 和 AOPP 的水平也通过 exendin-4 显著降低。
Exendin-4 治疗可改善 MGO 给药大鼠的 NO 介导的 CC 松弛，可能是通过抑制 NADPH 氧化酶。
