Rho Jeong Ho, Ko Il-Gyu, Jin Jun-Jang, Hwang Lakkyong, Kim Sang-Hoon, Chung Jun-Young, Hwang Tae-Jun, Han Jin Hee
Department of Anesthesiology and Pain Medicine, Okcheon St. Mary's Hospital, Okcheon, Korea.
Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
Int Neurourol J. 2020 Nov;24(Suppl 2):79-87. doi: 10.5213/inj.2040428.214. Epub 2020 Nov 23.
Adenosine A2A receptor agonist polydeoxyribonucleotide (PDRN) possesses an anti-inflammatory effect and suppress apoptotic cell death in several disorders. In this current study, the effect of PDRN on inflammation and apoptosis in rats with Achilles tendon injury was investigated.
von Frey filament test and plantar test were conducted for the determination of pain threshold. Analysis of histological alterations was conducted by hematoxylin and eosin staining. Immunohistochemistry for cleaved caspase-3-positive cells and cleaved caspase-9-positive cells was done. Enzyme-linked immunoassay was used to detect the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and cyclic adenosine-3',5'-monophosphate (cAMP). Western blot was conducted to detect the protein levels of cAMP response element-binding protein (CREB), protein kinase A (PKA), Bcl-2-associated X (Bax), and B-cell lymphoma 2 (Bcl-2).
PDRN treatment relieved mechanical allodynia and alleviated thermal hyperalgesia after Achilles tendon injury. TNF-α and IL-6 concentrations were decreased by PDRN application. PDRN injection significantly enhanced cAMP concentration and phosphorylated CREB versus CREB ratio, showing cAMP-PKA-CREB pathway was activated by PDRN application. PDRN treatment inhibited percentages of cleaved caspase-3-positive cells and caspase-9-posiive cells and the suppressed Bax versus Bcl-2 ratio in Achilles tendon injury rats.
PDRN is probably believed to have a good effect on pain and inflammation in the urogenital organs. PDRN may be used as a new treatment for Achilles tendon injury.
腺苷A2A受体激动剂聚脱氧核糖核苷酸(PDRN)在多种疾病中具有抗炎作用并抑制凋亡性细胞死亡。在本研究中,探究了PDRN对跟腱损伤大鼠炎症和凋亡的影响。
采用von Frey细丝试验和足底试验测定疼痛阈值。通过苏木精和伊红染色进行组织学改变分析。对裂解的半胱天冬酶-3阳性细胞和裂解的半胱天冬酶-9阳性细胞进行免疫组织化学检测。采用酶联免疫吸附测定法检测肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和环磷酸腺苷(cAMP)的浓度。进行蛋白质免疫印迹法检测cAMP反应元件结合蛋白(CREB)、蛋白激酶A(PKA)、Bcl-2相关X蛋白(Bax)和B细胞淋巴瘤-2(Bcl-2)的蛋白水平。
PDRN治疗可缓解跟腱损伤后的机械性异常性疼痛并减轻热痛觉过敏。应用PDRN可降低TNF-α和IL-6的浓度。与对照组相比,PDRN注射显著提高了cAMP浓度和磷酸化CREB与CREB的比值,表明PDRN激活了cAMP-PKA-CREB信号通路。PDRN治疗可抑制跟腱损伤大鼠中裂解的半胱天冬酶-3阳性细胞和半胱天冬酶-9阳性细胞的百分比,并降低Bax与Bcl-2的比值。
PDRN可能对泌尿生殖器官的疼痛和炎症有良好作用。PDRN可作为跟腱损伤的一种新的治疗方法。