Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2020-10-10 , DOI: 10.1016/j.jep.2020.113463 Ji-Sheng Wang 1 , Xiao Li 2 , Zi-Long Chen 1 , Jun-Long Feng 1 , Bing-Hao Bao 1 , Sheng Deng 1 , Heng-Heng Dai 1 , Fan-Chao Meng 1 , Bin Wang 3 , Hai-Song Li 3
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Ethnopharmacological relevance
Leeches (pinyin name Shui Zhi; Latin scientific name Hirudo;Hirudinea;Hirudinidae) and centipedes (pinyin name Wu Gong;Latin scientific name Scolopendridae;Chilopoda;Scolopendridae) are traditional Chinese medicines, and they belong to the family entomology. A combination of leech and centipede is used as an effective medicine to promote blood circulation and remove blood stasis in traditional Chinese medicine, and “leech-centipede” medicine has been used in many prescriptions to treat diabetic vascular disease, including diabetic erectile dysfunction(DIED). However, its specific mechanism remains unclear and requires in-depth study.
Aim of the study: This study aimed to investigate the mechanism of “leech-centipede” medicine to improve erectile dysfunction-associated diabetes by detecting PKC pathway-related molecules.
Materials and methods
The active ingredients of “leech-centipede” medicine were identified using high performance liquid chromatography (HPLC). Fifty male SPF rats were injected with streptozotocin to induce the DM model. Eight weeks later, the DMED model was validated with apomorphine. The DIED rats were divided into five groups—T,P,DD,DZ,and DG—and were separately treated with tadalafil,pathway inhibitor LY333531 and low-, medium-, and high-dose “leech-centipede” medicine for 8 weeks. After treatment, the blood glucose level was measured, erectile function with apomorphine was assessed, the LOX-1, sE-selectin, sICAM-1, SOD, and MDA in serum was evaluated by enzyme-linked immunosorbent assay, and flow cytometry was performed. After the collection of penile tissue, the related protein and mRNA expression was assessed by Western blotting and PCR, and the tissue and ultrastructure were analysed by HE staining, immunohistochemistry and scanning electron microscopy.
Results
After treatment, the erectile function of rats was significantly improved in the T,P,DD,DZ,and DG groups compared with that in the model group. Thus, “leech-centipede” medicine can significantly reduce the levels of LOX-1, sE-selectin, sICAM-1, EMPs and CD62P to protect vascular endothelial function and anti-platelet activation, improving DIED rat erectile function. Additionally, “leech-centipede” medicine can increase SOD expression and decrease MDA expression, reducing the possibility of oxidative stress injury in DIED rats and improving the antioxidant capacity. Moreover, “leech-centipede” therapy can dramatically reduce the protein and mRNA expression of DAG, PKCβ, NF-κB, and ICAM-1, improve vascular endothelial injury in DIED rats and inhibit abnormal platelet activation.
Conclusion
“leech-centipede” medicine can improve erectile dysfunction by inhibiting the expression of PKC pathway-related molecules in DIED rats and protects endothelial function and anti-platelet activation.
中文翻译：
水蛭蜈蚣药通过PKC信号通路相关分子改善死亡大鼠勃起功能的作用
民族药理学相关性
水蛭（拼音名Shuizhi；拉丁学名Hirudo；Hirudinea；Hirudinidae）和蜈蚣（拼音名WuGong；拉丁学名Scopenendridae；Chilopoda；Scolopendridae）均为传统中药，属于昆虫科。水蛭和蜈蚣的组合在中医中被用作活血化瘀的有效药物，“水蛭蜈蚣”药已被用于治疗糖尿病血管疾病的许多处方中，包括糖尿病勃起功能障碍（DIED） ）。但其具体机制尚不清楚，需要深入研究。
研究目的：本研究旨在通过检测PKC通路相关分子，探讨“水蛭蜈蚣”药物改善勃起功能障碍相关糖尿病的作用机制。
材料和方法
采用高效液相色谱法（HPLC）对“水蛭蜈蚣”药物的有效成分进行了鉴定。 50只雄性SPF大鼠注射链脲佐菌素诱导DM模型。八周后，DMED 模型用阿扑吗啡进行了验证。将死亡大鼠分为T、P、DD、DZ、DG 5组，分别给予他达拉非、通路抑制剂LY333531和低、中、高剂量“水蛭蜈蚣”药物治疗8周。 。治疗后测定血糖水平，用阿扑吗啡评估勃起功能，酶联免疫吸附法测定血清中LOX-1、sE-选择素、sICAM-1、SOD、MDA，并进行流式细胞仪检测。收集阴茎组织后，通过Western blotting和PCR评估相关蛋白和mRNA的表达，并通过HE染色、免疫组化和扫描电镜分析组织和超微结构。
结果
治疗后，T、P、DD、DZ、DG组大鼠勃起功能较模型组明显改善。由此可见，“水蛭蜈蚣”药可显着降低LOX-1、sE-选择素、sICAM-1、EMPs和CD62P的水平，保护血管内皮功能和抗血小板活化，改善DIED大鼠的勃起功能。此外，“水蛭-蜈蚣”药还能增加SOD表达，减少MDA表达，减少死亡大鼠氧化应激损伤的可能性，提高抗氧化能力。此外，“水蛭-蜈蚣”疗法可显着降低DAG、PKCβ、NF-κB、ICAM-1的蛋白和mRNA表达，改善DIED大鼠血管内皮损伤，抑制异常血小板活化。
结论
“水蛭蜈蚣”药可通过抑制DIED大鼠PKC通路相关分子的表达来改善勃起功能障碍，并保护内皮功能和抗血小板活化。
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