The effects of molsidomine on hypoxia inducible factor alpha and Sonic hedgehog in testicular ischemia/reperfusion injury in rats
The effects of molsidomine on hypoxia inducible factor alpha and Sonic hedgehog in testicular ischemia/reperfusion injury in rats
复制标题
DOI：
10.1007/s11255-008-9460-6
复制
发表时间：
2009-03-01
影响因子：
2
通讯作者：
Yilmaz, Fahri
中科院分区：
文献类型：
--
作者：
Dokucu, Ali Ihsan;Ozturk, Hulya;Yilmaz, Fahri
本研究旨在确定一氧化氮（NO）供体前体莫西多明（MO）对缺氧诱导因子α（HIF-1 α）和Sonic hedgehog（Shh）水平的影响，这些水平被认为与睾丸缺血/再灌注（I-R）损伤的发展有关。通过顺时针方向旋转同侧睾丸720 A度6 h和1 h进行睾丸复位来产生扭转。第1组（对照组，n = 7）进行假手术。在第2组（I-R/未处理，n = 7）中，单侧睾丸扭转6 h后，进行1 h睾丸复位。未给予药物。在第3组（I-R/MO）中，在进行与第2组相同的手术操作后，在再灌注开始时给予NO供体MO。第4组（I-R/L-NAME组），手术方法同第2组，在再灌注开始时给予L-NAME。测定睾丸丙二醛（MDA）水平，并进行睾丸组织学检查。与睾丸I-R组相比，MO治疗大鼠的MDA水平和组织病理学评分显著降低。与第1、2和4组相比，I-R/MO组中精子小管基底膜以及睾丸组织中支持细胞和生殖细胞中的Sonic hedgehog（Shh）表达显著增加。此外，I-R/MO组睾丸组织间质中HIF-1 α的表达显著增加。结果提示，MO对大鼠睾丸缺血再灌注损伤具有保护作用，并可能通过影响Shh和HIF-1 α信号通路发挥作用。
This study was designed to determine the effect of molsidomine (MO), a precursor of nitric oxide (NO) donor, on hypoxia inducible factor alpha (HIF-1 alpha) and Sonic hedgehog (Shh) levels considered to be involved in the development of testes ischemia/reperfusion (I-R) injury. Torsions were created by rotating ipsilateral testes 720A degrees in a clockwise direction for 6 h and 1-h detorsion of the testis was performed. A sham operation was performed in group 1 (control, n = 7). In group 2 (I-R/Untreated, n = 7), following 6 h of unilateral testicular torsion, 1-h detorsion of the testis was performed. No drug was given. In group 3 (I-R/MO), after performing the same surgical procedure as in group 2, a NO donor MO was given at the starting time of reperfusion. In group 4 (I-R/L-NAME), after performing the same surgical procedure as in group 2, L-NAME was given at the starting time of reperfusion. Testes malondialdehyde (MDA) levels were determined as well as examining the testes histologically. Treatment of rats with MO produced a significant reduction in the levels of MDA and histopathological score compared to testes I-R groups. The Sonic hedgehog (Shh) expression in the basement membrane of the tubuli seminiferi, and sertoli and germinal cells in testicular tissue, were greatly increased in the I-R/MO group compared to groups 1, 2 and 4. Additionally, the HIF-1 alpha expression in the interstitial spaces in testicular tissue were greatly increased in the I-R/MO group. The results suggest that MO has a protective effect against ischemia/reperfusion injury in rat testes and may affect Shh and HIF-1 alpha signaling pathway.