Paeonol ameliorates diabetic erectile dysfunction by inhibiting HMGB1/RAGE/NF‐kB pathway
Paeonol ameliorates diabetic erectile dysfunction by inhibiting HMGB1/RAGE/NF‐kB pathway
复制标题
丹皮酚通过抑制 HMGB1/RAGE/NF-kB 通路改善糖尿病勃起功能障碍
DOI：
10.1111/andr.13203
复制
发表时间：
2022-06
期刊：
影响因子：
4.5
通讯作者：
Jihong Liu
中科院分区：
文献类型：
--
作者：
Taotao Sun;Wenchao Xu;Jiaxin Wang;Jingyu Song;Tao Wang;Shaogang Wang;Kang Liu;Jihong Liu
糖尿病性勃起功能障碍（DMED）的管理由于患者数量的激增和DMED中磷酸二酯酶5型抑制剂的效率低下而逐渐变得棘手。丹皮酚（Pae）作为一种传统中药，在糖尿病并发症的治疗中得到越来越广泛的应用。为探讨Pae治疗DMED的药理作用及其可能机制，采用链脲佐菌素腹腔注射和阿朴吗啡实验建立DMED模型。17只DMED大鼠分为DMED组（n = 8）和DMED+Pae组（Pae; 100 mg/kg/d;口服; n = 9）。另取10只正常同龄雄性大鼠作为对照组。4周后，进行海绵体神经电刺激以测量勃起反应。此外，阴茎海绵体平滑肌细胞（CCSMC）的主要分离和暴露于高葡萄糖（HG）刺激，Pae治疗和白藜芦醇（GL; HMGB 1的选择性抑制剂）。DMED组大鼠阴茎勃起功能明显受损，HMGB 1/NF-κB通路表达上调。DMED组NO和cGMP水平较低，炎症、纤维化和细胞凋亡水平较高。结果表明，Pae治疗能改善大鼠勃起功能，并能引起组织学及相关分子的改变。Pae通过下调HMGB 1/NF-κB通路调节高糖条件下CCSMCs的凋亡和炎症水平，减轻DMED大鼠的艾德，其机制可能与抑制HMGB 1/NF-κB通路、炎症、凋亡和纤维化活性，减轻内皮功能障碍有关。我们的研究为DMED的潜在新疗法提供了证据。
The management of diabetes mellitus-induced erectile dysfunction (DMED) is progressively becoming tricky due to the surge in the number of patients and the poor efficiency of phosphodiesterase type 5 inhibitors in DMED. Paeonol (Pae), as a traditional Chinese medicine, has been more and more widely used in the treatment of diabetic complications. However, whether Pae could be a potential therapeutic drug of DMED needs to be further evaluated.To investigate the pharmacological effect and possible mechanism of Pae in the treatment of DMED.Intraperitoneal streptozotocin injection and an apomorphine test were used to construct the model of DMED. Seventeen DMED rats were divided into two groups: DMED group (n = 8) and DMED+Pae group (Pae; 100 mg/kg/d; oral administration; n = 9). In addition, there were still 10 normal age-matched male rats as control group. Four weeks later, the cavernous nerve electric stimulation was carried out to measure the erectile response. Moreover, the corpus cavernosum smooth muscle cells (CCSMCs) were primarily isolated and exposed to high glucose (HG) stimulation, Pae treatment and glycyrrhizin (GL; the selective inhibitor of HMGB1). After an incubation for 1 week, the CCSMCs were harvested for detection.The impairment of erectile function was observed in DMED rats compared with control samples, accompanied by the upregulation of HMGB1/RAGE/NF-κB Pathway. The lower nitric oxide and cGMP level and the higher level of inflammation, fibrosis, and apoptosis were also observed in DMED rats. It showed contrast that Pae treatment could improve the erectile function, as well as histologic alteration and related molecular changes. In addition, Pae could downregulate the HMGB1/RAGE/NF-κB pathway to regulate the apoptosis and inflammation levels of CCSMCs in high-glucose conditions, which is similar to the results of GL treatment.Pae alleviated ED in DMED rats, likely by inhibiting HMGB1/RAGE/NF-κB Pathway, inflammatory, apoptosis, and fibrotic activity, and moderating endothelial dysfunction. Our study provide evidence for a potential new therapy for DMED.
登录
查看更多内容
影响因子：
5.8
作者：
Li, Haiyan;Zhu, Jie;Zhang, Jiwen
通讯作者：
Zhang, Jiwen
影响因子：
29
作者：
Lerner AG;Upton JP;Praveen PV;Ghosh R;Nakagawa Y;Igbaria A;Shen S;Nguyen V;Backes BJ;Heiman M;Heintz N;Greengard P;Hui S;Tang Q;Trusina A;Oakes SA;Papa FR
通讯作者：
Papa FR
影响因子：
2.1
作者：
K. Shen;Q. Mao;Xiaoqin Yin;Chunyan Zhang;Yi Jin;Aiqing Deng;Z. Gu;Bohua Chen
通讯作者：
K. Shen;Q. Mao;Xiaoqin Yin;Chunyan Zhang;Yi Jin;Aiqing Deng;Z. Gu;Bohua Chen
影响因子：
6
作者：
Hongjie Qiao;Yuanyuan Zhang;Wenwen Lin;Yu-Feng Wang;C. Furdui;Qiuling Jiang;Xiao Li;Ting Long;Yunguang Wang;D. Qin
通讯作者：
Hongjie Qiao;Yuanyuan Zhang;Wenwen Lin;Yu-Feng Wang;C. Furdui;Qiuling Jiang;Xiao Li;Ting Long;Yunguang Wang;D. Qin
影响因子：
3.6
作者：
Qiu, Chen;Yang, Liu-Di;Wang, Min
通讯作者：
Wang, Min