Leech-Centipede Granules Suppress EndMT to Improve Erectile Dysfunction in Rats with Diabetes Mellitus via TGF-β/Smad Pathway

作者：Zhang, Hui; Feng, Chu-hui; He, Shan; Deng, Ming-xia; Meng, Hao; Chen, Ming; Liu, Hong^*

来源：Chinese Journal of Integrative Medicine, 2023, 29(1): 28-36.

DOI：10.1007/s11655-022-3728-z

• Leech-Centipede Granules
• erectile function
• diabetes mellitus
• endothelial cell
• endothelial-to-mesenchymal transition
• tumor growth factor-beta
• Smad pathway

Objective: To investigate whether Leech-Centipede (LC) Granules can improve erectile function in rats with diabetes mellitus-associated erectile dysDMED) through endothelial-to-mesenchymal transition (EndMT) inhibition. Methods: Components of LC Granules were identified via ultra-high-performance liquid chromatography. Thirty male Sprague Dawley rats were injected with streptozotocin and fed continuously for 8 weeks to establish the DMED rat model. Rats with erectile dysfunction symptoms diagnosed using apomorphine were divided into DMED and low-, medium-, and high-doses LC groups (n =6 in each). The negative control (NC, n =6) and DMED groups were given 5 mL of deionized water via intragastric gavage, and the low-, medium and the high-doses LC groups were administered LC at 1.6, 3.2, and 6.4 g/kg, respectively, via intragastric gavage for 4 weeks. The intracavernous pressure (ICP), mean arterial pressure (MAP), and nitric oxide (NO) levels in cavernous tissue were measured for each group. Quantitative reverse transcription-polymerase chain reaction and Western blot were used to detect mRNA and protein expressions of endothelial and mesenchymal markers. Immunofluorescence staining was used to observe alpha-SMA, and Masson's trichrome staining was performed to determine the myofiber/collagen ratio. Results: A total of 474 active components were identified. After treatment, the ICP/MAP value and NO level were significantly higher in the medium-and high-dose LC groups than in the DMED group (P < 0.05). Compared with the DMED groups, the medium-and high-dose groups LC significantly increased and decreased endothelial and mesenchymal markers expression, respectively (P < 0.05). Tumor growth factor (TGF)beta RII, p-Smad2, and p-Smad3 levels were considerably higher following diabetes onset but reduced following LC intervention (P < 0.05), except for TGF beta 1 (P > 0.05). alpha-SMA expression was significantly higher in the DMED group and was reduced in all LC intervention groups (P > 0.05). The myofiber/collagen ratio in the LC groups was higher than that in the DMED group but lower than that in the NC group (all P < 0.05). Conclusions: LC Granules may improve the erectile function of DMED rats by suppressing TGF-beta/Smad pathway to reverse EndMT.

• 单位
  广州中医药大学; 1