Testicular damage contributes to cyclosporine A (CsA) induced male infertility. However, the exact underlying molecular mediators involved in CsA-induced testis disorder remains unclear. The present study aimed to characterize the role of mir-34a/sirt-1 in CsA induced testicular injury alone or in combination with curcumin. A total of twenty-eight male Wistar rats were subdivided into four groups: control (Con), sham, cyclosporine A (CsA), cyclosporineA + curcumin (CsA + cur). The animals received cyclosporine A (30 mg/kg) and curcumin (40 mg/kg) for 28 days by oral gavage. At the end of the experiment, CsA administration significantly resulted in a decrease in testis weight and testis coefficient. The molecular analysis demonstrated that CsA exposure increased 8-OHdg and Nox4 protein contents in the testis tissue. TUNEL staining indicated that CsA caused the number of apoptotic cells to increase in the testes of male rats. In addition, exposure to CsA resulted in an increased expression of Bax, and a decreased expresion in that of Bcl-2, with a concomitant up-regulation of the Bax/Bcl-2, c-Caspase-3/p-Caspase-3 ratio and cytochrome c level. Meanwhile, exposure to CsA increased the expression of mir-34a and decreased sirt-1 protein level in the testis tissue samples compared to the control group. Taken together, our findings suggested that CsA can cause damage to testicular germ cells via oxidative stress and mitochondrial apoptotic pathway, and probably mir-34a/sirt-1 play a crucial role in this process. It also demonstrates that these negative effects of CsA can be reduced by using curcumin as an antioxidant and anti-inflammatory agent.

睾丸损伤会导致环孢素A（CsA）引起的男性不育。然而，尚不清楚参与CsA诱导的睾丸疾病的确切潜在分子介导物。本研究旨在表征mir-34a / sirt-1在单独或与姜黄素联用的CsA诱导的睾丸损伤中的作用。将总共​​二十八只雄性Wistar大鼠分为四组：对照组（Con），假手术，环孢菌素A（CsA），环孢菌素A +姜黄素（CsA + cur）。通过口服管饲法，动物接受环孢霉素A（30mg / kg）和姜黄素（40mg / kg）28天。实验结束时，CsA给药显着降低了睾丸重量和睾丸系数。分子分析表明，CsA暴露会增加睾丸组织中的8-OHdg和Nox4蛋白含量。TUNEL染色表明，CsA引起雄性大鼠睾丸中凋亡细胞的数量增加。此外，暴露于CsA导致Bax表达增加，而Bcl-2表达减少，同时Bax / Bcl-2，c-Caspase-3 / p-Caspase-3上调比和细胞色素c级。同时，与对照组相比，暴露于CsA可以增加睾丸组织样品中mir-34a的表达并降低sirt-1蛋白水平。两者合计，我们的发现表明，CsA可以通过氧化应激和线粒体凋亡途径对睾丸生殖细胞造成损害，而mir-34a / sirt-1可能在这一过程中起着至关重要的作用。它也证明了通过使用姜黄素作为抗氧化剂和抗炎药可以减少CsA的这些负面影响。