Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi, India.
Apoptosis. 2012 Jun;17(6):551-65. doi: 10.1007/s10495-012-0703-8.
The present study was aimed to investigate the beneficial effects of N-acetyl-L: -cysteine (NAC, 150 mg/kg bw twice/week) against testicular germ cell apoptosis in rats induced by chronic hCG administration (100 IU/rat/day for 30 days). NAC co-treatment improved serum testosterone, prevented rise in lipid peroxidation, intracellular H(2)O(2) and the activities of antioxidant enzymes in germ cells. Replenishment of intracellular GSH and total antioxidant capacity was seen. There was a marked reduction in TUNEL positive germ cells and expression of caspase-3 (p < 0.01) and PARP cleavage. Pro-apoptotic markers Fas, FasL, caspase-8 were also significantly downregulated. While Bcl-2 was fully restored, rise in Bax, caspase-9, phospho-JNK/JNK and phospho-c-Jun/c-Jun expression was significantly arrested. Anti-apoptotic phospho-Akt/Akt and NF-κB were otherwise found upregulated. Taken together, the above findings demonstrate that NAC intervention rescued the testicular germ cells from demise following chronic hCG treatment through regulation of multiple signaling mechanisms of metazoan apoptosis.
本研究旨在探讨 N-乙酰-L: -半胱氨酸（NAC，150mg/kg bw 每周两次）对慢性 hCG 给药（100IU/大鼠/天，30 天）诱导的大鼠睾丸生殖细胞凋亡的有益作用。NAC 共同治疗可改善血清睾酮，防止脂质过氧化、细胞内 H2O2 和生殖细胞抗氧化酶活性升高。细胞内 GSH 和总抗氧化能力得到补充。TUNEL 阳性生殖细胞明显减少，caspase-3（p<0.01）和 PARP 裂解表达降低。促凋亡标志物 Fas、FasL、caspase-8 也显著下调。Bcl-2 完全恢复，而 Bax、caspase-9、磷酸化-JNK/JNK 和磷酸化-c-Jun/c-Jun 表达显著受到抑制。相反，抗凋亡磷酸化-Akt/Akt 和 NF-κB 被发现上调。综上所述，这些发现表明，NAC 干预通过调节多细胞凋亡的多种信号机制，挽救了慢性 hCG 治疗后睾丸生殖细胞的死亡。
