Couplet medicines of leech and centipede granules improve erectile dysfunction via inactivation of the CaSR/PLC/PKC signaling in streptozotocin-induced diabetic rats
Couplet medicines of leech and centipede granules improve erectile dysfunction via inactivation of the CaSR/PLC/PKC signaling in streptozotocin-induced diabetic rats
复制标题
水蛭和蜈蚣颗粒联用通过灭活链脲佐菌素诱导的糖尿病大鼠的 CaSR/PLC/PKC 信号改善勃起功能障碍
DOI：
10.1042/bsr20193845
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发表时间：
2020-02-04
影响因子：
4
通讯作者：
Chen, Wang Qiang
中科院分区：
文献类型：
--
作者：
Ma, Jian Xiong;Wang, Bin;Chen, Wang Qiang
勃起功能障碍（ED）是糖尿病（DM）的重要并发症之一，CASR通过激活PKC在细胞抗凋亡和血管内皮NO生成中发挥重要作用。本研究旨在探讨水蛭蜈蚣颗粒（Leech and Centipede Granules， LCG）通过CaSR/PLC/PKC信号通路的作用。用链脲佐菌素诱导50只雄性sd大鼠DM模型。10周后，阿波吗啡试验证实DMED。DMED大鼠给予LCG和U73122灌胃4周。测量空腹血糖、体重、胰岛素和胰高血糖素水平。用阿波啡评价大鼠勃起功能。采用酶联免疫吸附法和流式细胞术检测血清，收集阴茎组织进行组织学和相关靶点表达分析。治疗后，LCG组的空腹血糖、体重、胰岛素、胰高血糖素水平和勃起功能均显著改善。LCG处理显著降低了LOX-1、NOX和EMPs浓度。LCG持续升高阴茎组织NO含量，降低ET-1含量。LCG和U73122也通过显著降低VCAM-1、ICAM-1和CD62P来改善阴茎纤维化。LCG还能降低阴茎细胞凋亡水平。此外，我们还观察到LCG对DMED大鼠CaSR/PLC/PKC通路的抑制作用。综上所述，LCG通过增加NO的生成，抑制内皮细胞凋亡和阴茎纤维化，显著改善DMED大鼠的勃起功能，这可能与抑制DMED大鼠的CaSR/PLC/PKC通路有关。
Abstract Erectile dysfunction (ED) is one of the significant complications of diabetes mellitus (DM), and CASR plays an important role in cellular antiapoptosis and NO production in the vascular endothelium by activating PKC. The present study was aimed to investigate the efficacy of Leech and Centipede Granules (LCG) through the CaSR/PLC/PKC signaling. Fifty male Sprague-Dawley rats were treated with streptozotocin to induce the DM model. After 10 weeks, an apomorphine test was used to confirm DMED. Rats with DMED were administrated with LCG and U73122 for 4 weeks. Fasting blood glucose, body weight, insulin and glucagon levels were measured. Erectile function in rats was assessed by apomorphine. Serums were measured using enzyme-linked immunosorbent assay and flow cytometry, and penile tissues were harvested for histologic and the expression of related targets analyses. After treatment, fasting blood glucose, body weight, insulin, glucagon levels, and erectile function were significantly ameliorated in the LCG groups. The LOX-1, NOX, and EMPs concentrations were significantly decreased with LCG treatment. LCG also continuously increased NO and decreased ET-1 content in penile tissues. LCG and U73122 administration also improved penile fibrosis by significantly decreasing VCAM-1, ICAM-1, and CD62P. The data also showed that LCG reduced the apoptosis level in the penis. Furthermore, the inhibited activation of the CaSR/PLC/PKC pathway was observed in DMED rats with LCG treatment. Collectively, LCG significantly ameliorated erectile function of DMED rats via increased NO generation, inhibiting endothelial cells apoptosis and penile fibrosis, which might benefit from the suppression of CaSR/PLC/PKC pathway in DMED rats.