Minutoli Letteria, Antonuccio Pietro, Romeo Carmelo, Nicòtina Piero Antonio, Bitto Alessandra, Arena Salvatore, Polito Francesca, Altavilla Domenica, Turiaco Nunzio, Cutrupi Antonio, Zuccarello Biagio, Squadrito Francesco
Department of Experimental and Clinical Medicine and Pharmacology, University of Messina, Italy.
Biol Reprod. 2005 Oct;73(4):730-6. doi: 10.1095/biolreprod.105.040741. Epub 2005 Jun 8.
Mitogen-activated protein kinase (MAPK) 3/MAPK1 (also known as ERK1/ERK2) plays an important role in the signal transduction pathways. To our knowledge, however, its role in the development of testicular ischemia-reperfusion injury has not yet been investigated. Therefore, we studied the pattern of MAPK3/MAPK1 activation in a experimental model of testicular ischemia-reperfusion injury. We also investigated MAPK8 to understand whether an association exists between these two MAPKs. Adult male Sprague-Dawley rats were subjected to 1 h of testicular ischemia followed by 24 h of reperfusion or to a sham testicular ischemia-reperfusion. Animals were randomized to receive PD98059, which is an inhibitor of MAPK3/MAPK1 (10 mg/kg i.p. administered immediately after detorsion), or its vehicle. The time course of MAPK3/MAPK1, MAPK8, and tumor necrosis factor (TNF; also known as TNF alpha) expression and a histological examination in both the ischemic-reperfused testis and the contralateral one were performed. In both testes, MAPK3/MAPK1 and MAPK8 expression appeared following 10 min of reperfusion and reached their highest activation after 30 min. The MAPK levels slowly decreased, and no significant expression of either kinase was observed following 2 h of reperfusion. Expression of TNF was evident after 1 h of reperfusion and reached its maximum increase after 3 h. PD98059 blunted MAPK3/MAPK1 and MAPK8, reduced TNF expression, and improved the testicular damage caused by ischemia-reperfusion injury in both testes. These data emphasize that MAPK3/MAPK1 has a role in testicular damage and that its blockade might have a future therapeutic role for the management of patients with unilateral testicular torsion.
丝裂原活化蛋白激酶（MAPK）3/MAPK1（也称为ERK1/ERK2）在信号转导通路中起重要作用。然而，据我们所知，其在睾丸缺血再灌注损伤发展中的作用尚未得到研究。因此，我们在睾丸缺血再灌注损伤的实验模型中研究了MAPK3/MAPK1的激活模式。我们还研究了MAPK8，以了解这两种丝裂原活化蛋白激酶之间是否存在关联。成年雄性Sprague-Dawley大鼠经历1小时的睾丸缺血，随后进行24小时的再灌注，或进行假睾丸缺血再灌注。动物被随机分配接受PD98059，它是MAPK3/MAPK1的抑制剂（在解除扭转后立即腹腔注射10mg/kg）或其溶剂。对缺血再灌注睾丸和对侧睾丸进行了MAPK3/MAPK1、MAPK8和肿瘤坏死因子（TNF；也称为TNFα）表达的时间进程以及组织学检查。在两个睾丸中，再灌注10分钟后出现MAPK3/MAPK1和MAPK8表达，并在30分钟后达到最高激活水平。丝裂原活化蛋白激酶水平缓慢下降，再灌注2小时后未观察到两种激酶的显著表达。再灌注1小时后TNF表达明显，3小时后达到最大增加。PD98059抑制了MAPK3/MAPK1和MAPK8，降低了TNF表达，并改善了双侧睾丸缺血再灌注损伤引起的睾丸损伤。这些数据强调MAPK3/MAPK1在睾丸损伤中起作用，其阻断可能对单侧睾丸扭转患者的治疗具有未来的治疗作用。
