Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China.
Hum Reprod. 2012 May;27(5):1300-13. doi: 10.1093/humrep/des063. Epub 2012 Mar 8.
Mounting evidence shows that nuclear factor-κB (NF-κB) plays an important role in endometriosis. We therefore evaluated the therapeutic potential of andrographolide, an NF-κB inhibitor.
Primary cell cultures were performed using ectopic endometrial tissue specimens and their homologous eutopic endometrial specimens from 16 women with endometriosis, as well as control samples from 4 women without endometriosis. Andrographolide was evaluated for an effect on cell proliferation and cell cycle, DNA-binding activity of NF-κB and expression of cyclooxygenase-2 (COX-2) and tissue factor (TF). In a rat model of endometriosis, andrographolide treatment was evaluated for an effect on lesion size, hotplate response latency and expression of phosphorylated p50 and p65, COX-2 and nerve growth factor (NGF) in ectopic endometrium.
Andrographolide dose dependently suppressed proliferation and cell cycle progression, attenuated DNA-binding activity of NF-κB in endometriotic stromal cells and inhibited COX-2 and TF expression. In the rat experiment, induced endometriosis resulted in reduced response latency. Andrographolide treatment significantly reduced lesion size in a dose-dependent manner and significantly increased response latency. Andrographolide treatment also significantly reduced immunoreactivity of COX-2, phosphorylated p50 and p65, and NGF in ectopic endometrium.
Treatment with andrographolide significantly suppresses the growth of ectopic endometrium in vitro and in vivo, and results in a significant improvement in generalized hyperalgesia in rats with induced endometriosis. Therefore, andrographolide may be cytoreductive and may relieve pain symptoms in women with endometriosis. With excellent safety and cost profiles, andrographolide could be a promising therapeutic agent for endometriosis.
越来越多的证据表明核因子-κB（NF-κB）在子宫内膜异位症中起着重要作用。因此，我们评估了 NF-κB 抑制剂穿心莲内酯的治疗潜力。
使用 16 名子宫内膜异位症患者的异位内膜组织标本及其同源的在位内膜标本以及 4 名无子宫内膜异位症患者的对照标本进行原代细胞培养。评估穿心莲内酯对细胞增殖和细胞周期、NF-κB 的 DNA 结合活性以及环氧化酶-2（COX-2）和组织因子（TF）的表达的影响。在子宫内膜异位症大鼠模型中，评估穿心莲内酯治疗对病变大小、热板反应潜伏期以及异位内膜中磷酸化 p50 和 p65、COX-2 和神经生长因子（NGF）表达的影响。
穿心莲内酯剂量依赖性地抑制增殖和细胞周期进程，减弱子宫内膜异位症基质细胞中 NF-κB 的 DNA 结合活性，并抑制 COX-2 和 TF 的表达。在大鼠实验中，诱导的子宫内膜异位症导致反应潜伏期缩短。穿心莲内酯治疗以剂量依赖性方式显著减小病变大小并显著增加反应潜伏期。穿心莲内酯治疗还显著降低异位内膜中 COX-2、磷酸化 p50 和 p65 以及 NGF 的免疫反应性。
穿心莲内酯治疗显著抑制体外和体内异位内膜的生长，并导致诱导子宫内膜异位症大鼠的全身痛觉过敏显著改善。因此，穿心莲内酯可能具有细胞毒性，并可缓解子宫内膜异位症妇女的疼痛症状。穿心莲内酯具有良好的安全性和成本效益，可能成为子宫内膜异位症有前途的治疗药物。
