Constantinescu Ioana M, Bolfa Pompei, Constantinescu Dan, Mironiuc Aurel I, Gherman Claudia D
Department of Surgery, Surgical Clinic II, "Iuliu Haţieganu" University of Medicine and Pharmacy Cluj-Napoca, 4-6 Clinicilor, 400006 Cluj-Napoca, Romania.
University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 3-5 Mănăştur, 400372 Cluj-Napoca, Romania.
Biomed Res Int. 2017;2017:9532381. doi: 10.1155/2017/9532381. Epub 2017 Jan 24.
. In this study, we aimed to demonstrate the role of sildenafil (an antagonist of phosphodiesterase type 5 (PDE-5)) and donepezil (a specific and reversible inhibitor of acetylcholinesterase (Ach)) in increasing ischemia-induced angiogenesis. . Critical limb ischemia was induced by ligation of the common femoral artery followed by ligation of the common iliac artery. The operated animals were divided into 3 groups: receiving sildenafil, receiving donepezil, and surgery alone; the contralateral lower limb was used as a negative control. The results were controlled based on clinical score and Doppler ultrasound. Gastrocnemius muscle samples were taken from all animals, both from the ischemic and nonischemic limb and were used for histopathological and immunohistochemical examination for the evaluation of the number of nuclei/field, endothelial cells (CD31), dividing cells (Ki-67), and vascular endothelial growth factor (VEGFR-3). . An increasing tendency of the number of nuclei/field with time was observed both in the case of sildenafil and donepezil treatment. The formation of new capillaries (the angiogenesis process) was more strongly influenced by donepezil treatment compared to sildenafil or no treatment. This treatment significantly influenced the capillary/fiber ratio, which was increased compared to untreated ligated animals. Sildenafil treatment led to a gradual increase in the number of dividing cells, which was significantly compared to the negative control group and compared to the ligation control group. The same effect (increase in the number of Ki-67 positive cells) was more obvious in the case of donepezil treatment. . Donepezil treatment has a better effect in ligation-induced ischemia compared to sildenafil, promoting angiogenesis in the first place, and also arteriogenesis.
在本研究中，我们旨在证明西地那非（一种磷酸二酯酶5型（PDE - 5）拮抗剂）和多奈哌齐（一种特异性且可逆的乙酰胆碱酯酶（Ach）抑制剂）在增加缺血诱导的血管生成中的作用。通过结扎股总动脉，随后结扎髂总动脉来诱导严重肢体缺血。将接受手术的动物分为3组：接受西地那非组、接受多奈哌齐组和单纯手术组；对侧下肢用作阴性对照。结果通过临床评分和多普勒超声进行对照。从所有动物的缺血和非缺血肢体采集腓肠肌样本，用于组织病理学和免疫组织化学检查，以评估细胞核/视野数量、内皮细胞（CD31）、分裂细胞（Ki - 67）和血管内皮生长因子（VEGFR - 3）。在西地那非和多奈哌齐治疗组中均观察到细胞核/视野数量随时间有增加趋势。与西地那非治疗或未治疗相比，多奈哌齐治疗对新毛细血管形成（血管生成过程）的影响更强。这种治疗显著影响毛细血管/纤维比率，与未治疗的结扎动物相比有所增加。西地那非治疗导致分裂细胞数量逐渐增加，与阴性对照组和结扎对照组相比有显著差异。在多奈哌齐治疗组中，相同的效果（Ki - 67阳性细胞数量增加）更为明显。与西地那非相比，多奈哌齐治疗在结扎诱导的缺血中效果更好，首先促进血管生成，还促进动脉生成。
