Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Andrology. 2014 Jan;2(1):76-82. doi: 10.1111/j.2047-2927.2013.00154.x. Epub 2013 Nov 26.
Ischaemic post-conditioning (IPostC) might represent an innovative surgical approach to protect organs from ischaemia and reperfusion (I/R) injury. We investigated the molecular mechanisms underlying the contrasting effects of IPostC on the early and late damage induced by testicular I/R injury. Testis I/R was induced by occluding the right testicular vessels using a clip. Male rats were divided into the following groups: sham, I/R and I/R + IPostC. In the I/R group, the clip was removed after 60 min of ischaemia, and reperfusion was allowed for 30 min, 1 and 30 days. In the I/R + IPostC group, three cycles of 30-sec reperfusion and 30-sec ischaemia were performed after 60 min of ischaemia and then reperfusion followed up for 30 min, 1 and 30 days. Following 30-min reperfusion, there was an increase in mitogen-activated protein kinases (MAPKs) in I/R rats; after 1 day of reperfusion, interleukin-6, tumour necrosis factor-α and nuclear factor-κB (NF-κB) expression were significantly increased; IκB-α expression reduced; and a marked damage in both testes was observed. IPostC inhibited MAPKs, cytokines and NF-κB expression, augmented IκB-α expression and decreased histological damage in testes subjected to I/R. After 30 days of reperfusion, I/R injury activated the apoptosis machinery, caused severe histological damage and reduced spermatogenic activity. By contrast, IPostC did not modify the apoptotic markers, the histological alterations as well as spermatogenic activity following 30 days of reperfusion. Our data demonstrate that IPostC protects the testis from the early damage induced by I/R injury, but it does not protect against the late damage.
缺血后处理(IPostC)可能代表了一种保护器官免受缺血再灌注(I/R)损伤的创新手术方法。我们研究了 IPostC 对睾丸 I/R 损伤引起的早期和晚期损伤的分子机制。通过夹闭右侧睾丸血管来诱导睾丸 I/R。雄性大鼠分为以下几组:假手术组、I/R 组和 I/R+IPostC 组。在 I/R 组中,夹闭 60 分钟后去除夹子,允许再灌注 30 分钟、1 天和 30 天。在 I/R+IPostC 组中,在缺血 60 分钟后进行三次 30 秒的再灌注和 30 秒的缺血,然后再灌注 30 分钟、1 天和 30 天。再灌注 30 分钟后,I/R 大鼠的丝裂原活化蛋白激酶(MAPKs)增加;再灌注 1 天后,白细胞介素-6、肿瘤坏死因子-α和核因子-κB(NF-κB)表达显著增加;IκB-α表达减少;并且观察到睾丸明显损伤。IPostC 抑制了 MAPKs、细胞因子和 NF-κB 的表达,增加了 IκB-α 的表达,减轻了 I/R 睾丸的组织损伤。再灌注 30 天后,I/R 损伤激活了凋亡机制,导致严重的组织损伤和精子发生活性降低。相比之下,IPostC 并未改变再灌注 30 天后的凋亡标志物、组织改变以及精子发生活性。我们的数据表明,IPostC 可保护睾丸免受 I/R 损伤引起的早期损伤,但不能防止晚期损伤。