【摘要】 目的 探讨格尔德霉素在大鼠脑缺血/再灌注神经损伤保护中的分子机制。方法 清洁级SD大鼠，建立四动脉结扎法大鼠脑缺血模型。SD大鼠随机分组，每组6只：(1) Sham组，仅手术，不进行缺血/再灌注；(2)脑缺血/再灌注6 h组(I/R组);(3)溶剂对照组(D+I/R组),缺血前20 min溶剂20μl/kg脑室注射；(4)格尔德霉素组(G+I/R组),缺血前20 min格尔德霉素20μl/kg脑室注射。采用免疫组化和免疫印迹技术检测格尔德霉素对脑缺血/再灌注后HSP90的表达和P38蛋白激酶的磷酸化水平。结果 再灌注6 h的格尔德霉素组HSP90的蛋白表达量和P38的磷酸化水平与I/R组相比较显著降低(P<0.05)。结论 格尔德霉素通过抑制HSP90的表达及P38蛋白激酶的磷酸化发挥缺血/再灌注脑损伤保护作用。更多还原

【Abstract】 Objective To investigate the molecular mechanism of geldanamycin to prevent rat nerve injury after cerebral ischemia/reperfusion. Methods Adult male Sprague-Dawley rats weighing 250-300 g were adopted to establish a cerebral ischemia model through occlusions of bilateral common carotid and vertebral arteries. These animals were randomly divided into the following groups(n=6): a sham operation group, an I/R group, a solvent group which was injected with 20 μl/kg solvent 20 min before ischemia, and a geldanamycin group which was injected with 20 μl/kg geldanamycin 20 min before ischemia. Then, the levels of HSP90 and phosphorylated P38 kinase in the hippocampus were measured by immunohistochemistry and western blotting. Results After reperfusion for 6 h, the geldanamycin group produced obviously decreased levels of HSP90 and phosphorylated P38 kinase than the I/R group(P<0.05). Conclusion Geldanamycin can exert neuroprotective effects through inhibiting the amount of HSP90 and blocking the phosphorylation of P38 kinase.更多还原