Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 450052, Henan, PR China.
Int Immunopharmacol. 2011 Nov;11(11):1925-31. doi: 10.1016/j.intimp.2011.08.001. Epub 2011 Aug 16.
Previous studies have demonstrated that progesterone (PROG) may be a pleiotropic neuroprotective agent. Although there have been reports about the neurotoxicity of activated microglia and cyclooxygenase-2 (COX-2) in animal models of ischemic stroke, the influence of PROG on the activation of microglia and the expression of COX-2 after stroke has not been examined in detail. In this investigation, we carried out research about the influence of PROG on cultured microglia by detection of the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in their supernatant fluid before and after induced with lipopolysaccharide (LPS) or influenced by PROG with Enzyme-Linked Immunosorbent Assay technique in vitro. Moreover, the expression of COX-2 and ionized calcium-binding adapter molecule 1 (Iba1) was also detected in the cortex of rats that underwent permanent middle cerebral artery occlusion and received PROG or vehicle treatment by immunohistochemistry and western blot technique. The results revealed that PROG significantly reduced the expression of TNF-α and IL-1β in cultured microglia after activated with LPS in vitro. In addition, PROG also valuably inhibited the expression of Iba1 and COX-2 after stroke in vivo. These observations raised the possibility that PROG can exert its neuroprotective effects by inhibiting the activation of microglia and the over expression of COX-2 after stroke.
先前的研究表明孕激素（PROG）可能是一种多效神经保护剂。尽管有报道称在缺血性中风的动物模型中，激活的小胶质细胞和环氧化酶-2（COX-2）具有神经毒性，但 PROG 对中风后小胶质细胞的激活和 COX-2 的表达的影响尚未被详细研究。在这项研究中，我们通过酶联免疫吸附试验（Enzyme-Linked Immunosorbent Assay technique）体外检测脂多糖（LPS）诱导前后培养的小胶质细胞上清液中肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达，研究了 PROG 对培养的小胶质细胞的影响。此外，还通过免疫组织化学和 Western blot 技术检测了接受 PROG 或载体治疗的永久性大脑中动脉闭塞大鼠皮质中 COX-2 和离子钙结合衔接分子 1（Iba1）的表达。结果表明，PROG 可显著降低 LPS 体外激活后培养的小胶质细胞中 TNF-α和 IL-1β的表达。此外，PROG 还可有效抑制体内中风后 Iba1 和 COX-2 的表达。这些观察结果表明，PROG 通过抑制中风后小胶质细胞的激活和 COX-2 的过度表达发挥其神经保护作用的可能性。
