1Departments of Biochemistry and Molecular Biology.
Int J Neurosci. 2014 Jan;124(1):42-8. doi: 10.3109/00207454.2013.817407. Epub 2013 Jul 19.
Recent studies found that progesterone (PROG) has a noticeable preventive effect on brain injuries. However, the underlying mechanisms of these effects, particularly on hypoxic ischemic brain damage (HIBD), remain unclear. This study observed the influence of PROG on the expression of cycloxygenase-2 (COX-2) and interleukin-1β (IL-1β) in HIBD neonatal rats, and explored the corresponding molecular mechanisms underlying the neuroprotective effect of PROG. Sixty 7-day-old neonatal Wistar rats were divided into sham operation (control), hypoxic ischemia (HI), and drug prophylaxis (PROG) groups, and HIBD animal models were routinely established. The PROG group was intraperitoneally injected with 0.5 g/L PROG at a dosage of 8 mg/kg 30 min before establishment of the model. All the animals were sacrificed 24 h after modeling. Changes in the COX-2 and IL-1β contents in the brain tissues were determined using enzyme-linked immunosorbent assay. Protein expression was observed using immunohistochemistry, and mRNA expression was determined using reverse transcription polymerase chain reaction. The expression and contents of COX-2 and IL-1β in the HI group were significantly higher than those in the control group (P < 0.01). Compared with the HI group, the PROG group showed noticeably lower expression and contents of COX-2 and IL-1β (P < 0.05). In conclusion, PROG can inhibit the expression of COX-2 and IL-1β in brain tissue, further reducing the level of COX-2 and IL-1β, which may be one of the mechanisms for protection from HIBD.
近期研究发现孕激素(PROG)对脑损伤具有显著的预防作用。然而,这些作用的潜在机制,特别是对缺氧缺血性脑损伤(HIBD)的作用机制尚不清楚。本研究观察了 PROG 对 HIBD 新生大鼠环氧化酶-2(COX-2)和白细胞介素-1β(IL-1β)表达的影响,并探讨了 PROG 神经保护作用的相应分子机制。将 60 只 7 日龄新生 Wistar 大鼠分为假手术(对照)、缺氧缺血(HI)和药物预防(PROG)组,常规建立 HIBD 动物模型。PROG 组于模型建立前 30 min 腹腔注射 0.5 g/L PROG 剂量为 8 mg/kg。所有动物均在建模后 24 h 处死。采用酶联免疫吸附试验检测脑组织中 COX-2 和 IL-1β含量的变化。采用免疫组织化学法观察蛋白表达,逆转录聚合酶链反应法检测 mRNA 表达。HI 组 COX-2 和 IL-1β的表达和含量明显高于对照组(P<0.01)。与 HI 组相比,PROG 组 COX-2 和 IL-1β的表达和含量明显降低(P<0.05)。综上所述,PROG 可抑制脑组织中 COX-2 和 IL-1β的表达,进一步降低 COX-2 和 IL-1β的水平,这可能是其对 HIBD 保护作用的机制之一。