Department of Urology, Tao-Yuan General Hospital, Department of Health, Taoyuan 330, Taiwan.
Toxicol Lett. 2011 Dec 15;207(3):242-50. doi: 10.1016/j.toxlet.2011.09.016. Epub 2011 Sep 24.
We evaluate the protective role of simvastatin-induced HO-1 in remote preconditioning against testis ischemia-reperfusion (IR) injury in vivo. Simvastatin was intraperitoneally (i.p.) injected 24 h before IR injury. Testis was occluded in the right testis for 40 min and followed by 30 min of reperfusion to induce IR injury. Tin protoporphyrin (Snpp), a competitive inhibitor of hemeoxygenase, was i.p. injected 1 h before the IR injury in separate groups of rats. The rat testes were harvested 24 h later. Induction of HO-1 expression by simvastatin was significantly increased at 24 and 48 h. Rats pre-treated with simvastatin showed higher expression of HO-1 protein by Western blotting and immunohistochemistry (IHC), and presented lower caspases-3 activity by caspase-3 activity assay. TUNEL staining analysis revealed simvastatin pretreatment significantly reduced IR induced cellular apoptosis. Contrarily, the simvastatin-induced cytoprotective effect was entirely abolished by administrations of Snpp. Further, lower caspase-3 activities were also noted in simvastatin plus Snpp (SS) group than the control plus Snpp (CS) group. After IR injury, eNOS immunoreactivity was markedly increased in the germ cell and Leydig cell of testicular tissues. Pretreatment of simvastatin significantly decreased eNOS immunoreactivity in the germ cell of the tubules in the rat testes. In conclusion, we suggest HO-1 plays a protective role in IR-induced injury in the testes of rats.
我们评估了辛伐他汀诱导的 HO-1 在体内对远隔预处理预防睾丸缺血再灌注 (IR) 损伤的保护作用。辛伐他汀在 IR 损伤前 24 小时腹腔内 (i.p.) 注射。右侧睾丸夹闭 40 分钟，然后再灌注 30 分钟以诱导 IR 损伤。锡原卟啉 (Snpp)，一种血红素加氧酶的竞争性抑制剂，在单独的大鼠组中于 IR 损伤前 1 小时腹腔内注射。24 小时后收获大鼠睾丸。辛伐他汀诱导的 HO-1 表达在 24 和 48 小时时显著增加。用辛伐他汀预处理的大鼠通过 Western blot 和免疫组织化学 (IHC) 显示出更高的 HO-1 蛋白表达，通过 caspase-3 活性测定显示出更低的 caspase-3 活性。TUNEL 染色分析表明，辛伐他汀预处理可显著减少 IR 诱导的细胞凋亡。相反，用 Snpp 给予辛伐他汀诱导的细胞保护作用完全被消除。此外，在辛伐他汀加 Snpp (SS) 组中也观察到比对照加 Snpp (CS) 组更低的 caspase-3 活性。IR 损伤后，睾丸组织中生殖细胞和间质细胞的 eNOS 免疫反应性明显增加。辛伐他汀预处理可显著降低大鼠睾丸小管生殖细胞中的 eNOS 免疫反应性。总之，我们认为 HO-1 在大鼠睾丸 IR 诱导损伤中发挥保护作用。
