Taidi Zhinoos, Zhou Tommy, Moore Kate H, Mansfield Kylie J, Liu Lu
School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia.
St George Hospital, UNSW Sydney, Kogarah, NSW, Australia.
Front Pharmacol. 2021 Aug 12;12:682520. doi: 10.3389/fphar.2021.682520. eCollection 2021.
Inflammatory conditions of the urinary bladder have been shown to be associated with urothelial damage and loss of function. The purinergic P2X7 receptor has been implicated in several inflammatory conditions. The aim of this study was to investigate the role of the P2X7 receptor in acrolein-induced inflammatory damage using the porcine urinary bladder. For this purpose, an model of porcine urothelial damage induced by direct instillation of acrolein into the whole bladder lumen was used. To determine the role of the P2X7 receptor, the bladders were pre-incubated with a selective P2X7 receptor antagonist, A804598 (10 μM), for 1 h. The effects of the acrolein-induced urothelial damage on the bladder's function were assessed by examining the bladder wall contractile response, structure changes, apoptosis, and oxidative stress in the bladder tissues. The acrolein treatment led to significant damage to the urothelium histology, tight junction expression, and contractile responses. Acrolein also induced apoptosis in the mucosa layer. All these acrolein-induced responses were attenuated by pre-treatment with the P2X7 receptor antagonist A804598. Acrolein also significantly induced DNA oxidation in the submucosal layer; however, the P2X7 receptor antagonism did not show any protective effect towards the acrolein-induced oxidative stress. These findings suggested that the P2X7 receptor is involved in the acrolein-induced damage to the urothelium; therefore, the P2X7 receptor antagonists may be a new therapeutic option for the treatment of bladder inflammation.
膀胱的炎症状态已被证明与尿路上皮损伤和功能丧失有关。嘌呤能P2X7受体与多种炎症状态有关。本研究的目的是利用猪膀胱研究P2X7受体在丙烯醛诱导的炎症损伤中的作用。为此，采用了将丙烯醛直接滴入整个膀胱腔诱导猪尿路上皮损伤的模型。为了确定P2X7受体的作用，将膀胱用选择性P2X7受体拮抗剂A804598（10 μM）预孵育1小时。通过检查膀胱壁的收缩反应、结构变化、细胞凋亡和膀胱组织中的氧化应激，评估丙烯醛诱导的尿路上皮损伤对膀胱功能的影响。丙烯醛处理导致尿路上皮组织学、紧密连接表达和收缩反应的显著损伤。丙烯醛还诱导黏膜层细胞凋亡。所有这些丙烯醛诱导的反应都被P2X7受体拮抗剂A804598预处理减弱。丙烯醛还显著诱导黏膜下层的DNA氧化；然而，P2X7受体拮抗作用对丙烯醛诱导的氧化应激没有显示出任何保护作用。这些发现表明，P2X7受体参与了丙烯醛诱导的尿路上皮损伤；因此，P2X7受体拮抗剂可能是治疗膀胱炎症的一种新的治疗选择。
