Increased expression of Leydig cell haem oxygenase-1 preserves spermatogenesis in varicocele.

Increased expression of Leydig cell haem oxygenase-1 preserves spermatogenesis in varicocele.
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DOI:
10.1093/humrep/dei063
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发表时间:
2005-09
期刊:
影响因子:
6.1
通讯作者:
Koji Shiraishi;K. Naito
Koji Shiraishi;K. Naito
中科院分区:
医学1区
文献类型:
--
作者:
Koji Shiraishi;K. Naito

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氧化应激参与睾丸疾病的发病机制。血红素氧合酶-1(HO-1)在抗氧化应激中起重要的细胞保护作用。我们研究了人类精索静脉曲张睾丸中氧化应激的存在,以4-羟基-2-壬烯醛(4-HNE)修饰蛋白的产生为代表,以及HO-1的表达。方法收集30例左侧精索静脉曲张患者和10例正常生精患者的睾丸活检标本。4-HNE修饰的蛋白质的产生被检查作为氧化应激的标志物。采用免疫印迹法和免疫组化法检测HO-1的表达。将其表达与临床病理参数进行比较。结果精索静脉曲张睾丸组织中4-HNE修饰蛋白的表达增加。HO-1表达与精索静脉曲张分级(2级和3级与对照组相比P <0.01)和4-HNE修饰蛋白表达显著相关(r = 0.508,P <0.01)。精索静脉曲张睾丸间质细胞免疫反应增强。HO-1:4-HNE修饰蛋白比值与年龄、活动精子总数、Johnsen评分均呈正相关(r分别为0.206、0.405和0.408,P分别为0.027、0.027和0.025)。结论:在精索静脉曲张的睾丸中,4-HNE修饰的蛋白质增加,表明存在氧化应激。HO-1主要在睾丸间质细胞中表达增加,被认为可以保护精索静脉曲张睾丸细胞免受氧化应激。
BACKGROUND Oxidative stress is involved in the pathogenesis of testicular disorders. Haem oxygenase-1 (HO-1) plays an important cytoprotective role against oxidative stress. We investigated the presence of oxidative stress, represented by generation of 4-hydroxy-2-nonenal (4-HNE)-modified proteins, and expression of HO-1 in varicocele testes of human. METHODS Thirty testicular biopsies from patients with left varicocele and 10 from patients with normal spermatogenesis were included. Generation of 4-HNE-modified proteins was examined as a marker of oxidative stress. Expression of HO-1 was assessed by western blotting and immunohistochemistry. The expression was compared with clinico-pathological parameters. RESULTS Increased generation of 4-HNE-modified proteins was observed in varicocele testes. HO-1 expression was significantly correlated with varicocele grade (P < 0.01 in grade 2 and 3 compared to control) and expression of 4-HNE-modified proteins (r = 0.508, P < 0.01). The immunoreactivity was increased in Leydig cells in varicocele testes. There were significant correlations between age, total motile sperm count, Johnsen's mean score and HO-1:4-HNE-modified protein ratio (r = 0.206, 0.405 and 0.408, P = 0.027, 0.027 and 0.025 respectively). CONCLUSIONS In testes with varicocele, there are increases in 4-HNE-modified proteins, suggesting that oxidative stress is present. Increased HO-1 expression, mainly in Leydig cells, is considered to protect the cells against oxidative stresses in varicocele testes.