Zhu Bingbing, Niu Yangjiu, Niu Lipan, Zhang Xijia, Liu Fengxia
Department of Human Anatomy, School of Basic Medical Science, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830011, China.
Sex Med. 2023 Aug 25;11(4):qfad044. doi: 10.1093/sexmed/qfad044. eCollection 2023 Aug.
Inflammation is a key risk factor for heart disease and has also been linked to erectile dysfunction (ED). Sildenafil is a phosphodiesterase type 5 inhibitor with a strong antioxidant effect. Interleukin (IL)-18 is a proinflammatory factor. Excessive production and release of IL-18 disrupt the balance between IL-18 and IL-18 binding proteins in certain inflammatory diseases, leading to the occurrence of pathological inflammation.
We evaluated the effects of sildenafil on erectile function in a rat model of high-fat diet-induced ED.
Male Sprague Dawley rats (6 weeks old) were divided into 5 groups: control, ED, sildenafil, IL-18, and IL-18 + sildenafil. Subsequently, intracavernous pressure and mean arterial pressure were used to assess the erectile function of these rats. The expression of endothelial nitric oxide synthase, pyroptosis factors, and the ratio of smooth muscle cells and collagen fibers were evaluated in the serum and corpora tissue.
Exploring the role and mechanism of sildenafil in ED through NLRP3-mediated pyroptosis pathway.
In comparison to the ED and IL-18 groups, there were statistically significant increases in the ratio of intracavernous pressure to mean arterial pressure, endothelial nitric oxide synthase expression, and the ratio of smooth muscle cells to collagen fibers following sildenafil intervention ( < .05). The sildenafil group and IL-18 + sildenafil group also showed statistically significant decreases the expression of NLRP3, caspase-1, and gasdermin D ( < .05).
Sildenafil can improve erectile dysfunction by inhibiting inflammation.
Strengths are that the relationship between pyroptosis and ED has been verified through in vitro and in vivo experiments. The limitation is that the conclusions drawn from animal and cells experiments need to be confirmed in clinical research.
Sildenafil may reduce the effect of IL-18-induced inflammation in high-fat diet-induced ED rats through NLRP3/caspase-1 pyroptosis pathway.
炎症是心脏病的关键危险因素，也与勃起功能障碍（ED）有关。西地那非是一种具有强大抗氧化作用的5型磷酸二酯酶抑制剂。白细胞介素（IL）-18是一种促炎因子。在某些炎症性疾病中，IL-18的过度产生和释放会破坏IL-18与IL-18结合蛋白之间的平衡，导致病理性炎症的发生。
我们评估了西地那非对高脂饮食诱导的ED大鼠模型勃起功能的影响。
将6周龄雄性Sprague Dawley大鼠分为5组：对照组、ED组、西地那非组、IL-18组和IL-18+西地那非组。随后，采用海绵体内压和平均动脉压评估这些大鼠的勃起功能。评估血清和海绵体组织中内皮型一氧化氮合酶、焦亡因子的表达以及平滑肌细胞与胶原纤维的比例。
探索西地那非通过NLRP3介导的焦亡途径在ED中的作用和机制。
与ED组和IL-18组相比，西地那非干预后海绵体内压与平均动脉压的比值、内皮型一氧化氮合酶表达以及平滑肌细胞与胶原纤维的比例有统计学显著增加（P<0.05）。西地那非组和IL-18+西地那非组的NLRP3、半胱天冬酶-1和gasdermin D表达也有统计学显著降低（P<0.05）。
西地那非可通过抑制炎症改善勃起功能障碍。
优点是通过体外和体内实验验证了焦亡与ED之间的关系。局限性是动物和细胞实验得出的结论需要在临床研究中得到证实。
西地那非可能通过NLRP3/半胱天冬酶-1焦亡途径降低高脂饮食诱导的ED大鼠中IL-18诱导的炎症作用。
