Yao Xiaolin, Yuan Yufang, Jing Taile, Ye Sunyi, Wang Shuo, Xia Dan
Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Transl Androl Urol. 2022 Jul;11(7):982-995. doi: 10.21037/tau-22-428.
Diabetes mellitus-induced erectile dysfunction (DMED) is a frequent complication of diabetes mellitus (DM), with limited therapy at present. This study aimed to explore the role and mechanism of Ganoderma lucidum polysaccharide (GLP) on DMED.
DMED was induced in the experimental rats [male 12-week-old Sprague-Dawley (SD) rats] by treatment with streptozotocin (60 mg/kg) and apomorphine (APO). Next, rats in the GLP low dose (GLP-L)/GLP high dose (GLP-H) groups were treated with GLP (100 or 400 mg/kg/d, respectively) for 8 weeks. Subsequently, erectile function was assessed by APO and electrostimulation of the cavernous nerve (CN). Serum or penile testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cyclic guanosine monophosphate (cGMP) contents were evaluated by enzyme-linked immunosorbent assay (ELISA). The levels of oxidative stress indicators in the corpus cavernosum (CC) were measured by corresponding kits, and histological changes in the CC were observed by hematoxylin-eosin (HE) and Masson staining. Additionally, the apoptosis index, caspase-3, caspase-9, and eNOS expression, and mitochondrial membrane potential (MMP) were also detected. Furthermore, quantitative polymerase chain reaction (qPCR) and western blot assays were conducted to determine the , mRNA expression, ERK1/2, eNOS, JNK phosphorylation, and arginase II protein expression.
The erectile function test revealed that erectile dysfunction (ED) was alleviated in the DMED rats following treatment with GLP. Moreover, GLP upregulated the T and cGMP content, improved the oxidative stress and histological injuries of CC, and also inhibited the apoptosis and MMP loss of penile tissues in DMED rats. Furthermore, GLP treatment enhanced the mRNA expression of and and suppressed the phosphorylation of ERK1/2, eNOS, and JNK, as well as the protein expression of arginase II in DMED rats.
GLP ameliorated DMED by repairing the CC pathological damage and upregulating expression and ERK/JNK phosphorylation, indicating that GLP may be a candidate drug for DMED therapy.
糖尿病性勃起功能障碍（DMED）是糖尿病（DM）的常见并发症，目前治疗方法有限。本研究旨在探讨灵芝多糖（GLP）对DMED的作用及机制。
通过链脲佐菌素（60mg/kg）和阿扑吗啡（APO）处理诱导实验大鼠（12周龄雄性Sprague-Dawley大鼠，即SD大鼠）发生DMED。接下来，GLP低剂量（GLP-L）/GLP高剂量（GLP-H）组大鼠分别用GLP（100或400mg/kg/d）处理8周。随后，通过APO和海绵体神经（CN）电刺激评估勃起功能。采用酶联免疫吸附测定（ELISA）法评估血清或阴茎中的睾酮（T）、黄体生成素（LH）、卵泡刺激素（FSH）和环磷酸鸟苷（cGMP）含量。用相应试剂盒测定海绵体（CC）中氧化应激指标水平，通过苏木精-伊红（HE）染色和Masson染色观察CC的组织学变化。此外，还检测了凋亡指数、半胱天冬酶-3、半胱天冬酶-9和内皮型一氧化氮合酶（eNOS）表达以及线粒体膜电位（MMP）。此外，进行定量聚合酶链反应（qPCR）和蛋白质免疫印迹分析以确定 、 mRNA表达、细胞外信号调节激酶1/2（ERK1/2）、eNOS、应激活化蛋白激酶（JNK）磷酸化以及精氨酸酶II蛋白表达。
勃起功能测试显示，GLP处理后的DMED大鼠勃起功能障碍（ED）得到缓解。此外，GLP上调了T和cGMP含量，改善了CC的氧化应激和组织学损伤，还抑制了DMED大鼠阴茎组织的凋亡和MMP丧失。此外，GLP处理增强了DMED大鼠 和 的mRNA表达，并抑制了ERK1/2、eNOS和JNK的磷酸化以及精氨酸酶II的蛋白表达。
GLP通过修复CC病理损伤并上调 表达和ERK/JNK磷酸化改善了DMED，表明GLP可能是DMED治疗的候选药物。
