Department of Anesthesiology, Gongli Hospital, Pudong, Shanghai, China.
Crit Care Med. 2010 Nov;38(11):2190-8. doi: 10.1097/CCM.0b013e3181f17bcb.
Elderly patients undergoing major surgery often develop cognitive dysfunction and the mechanism of this postoperative complication remains elusive. We sought to determine whether postoperative cognitive dysfunction in old mice is associated with the pathogenesis of Alzheimer's disease.
Prospective, randomized study.
University teaching hospital-based research laboratory.
One-hundred and twenty C57BL/6 14-mo-old male mice (weighing 30-40 g).
Mice received intraperitoneal injections of either vehicle or Celastrol (a potent anti-inflammatory compound) for 3 days before undergoing sham surgery or partial hepatectomy, on the surgery day, and for a further 4 days after surgery. Cognitive function, hippocampal neuroinflammation, and pathologic markers of Alzheimer's disease were assessed 1 day after surgery day 1, 3, or 7.
Cognitive impairment following surgery was associated with the appearance of certain pathologic hallmarks of Alzheimer's disease: microgliosis, astrogliosis, enhanced transcriptional and translational activity of β-amyloid precursor protein, β-amyloid production, and τ protein hyperphosphorylation in the hippocampus. Surgery-induced changes in cognitive dysfunction were prevented by the administration of Celastrol as were changes in β-amyloid and τ processing.
These data suggest that surgery can provoke astrogliosis, β-amyloid accumulation, and τ phosphorylation in old subjects, which is likely to be associated with the cognitive decline seen in postoperative cognitive dysfunction.
接受大手术的老年患者常发生认知功能障碍，其术后并发症的发病机制仍难以捉摸。我们试图确定老年小鼠术后认知功能障碍是否与阿尔茨海默病的发病机制有关。
前瞻性、随机研究。
大学教学医院的研究实验室。
120 只 C57BL/6 14 月龄雄性小鼠（体重 30-40g）。
在接受假手术或部分肝切除术之前，小鼠连续 3 天腹腔注射载体或 Celastrol（一种有效的抗炎化合物），在手术当天以及手术后的另外 4 天继续注射。在手术后第 1、3 或 7 天，评估认知功能、海马神经炎症和阿尔茨海默病的病理标志物。
手术后认知障碍与阿尔茨海默病的某些病理特征的出现有关：小胶质细胞增生、星形胶质细胞增生、β-淀粉样前体蛋白转录和翻译活性增强、β-淀粉样蛋白产生和τ蛋白过度磷酸化。Celastrol 的给药可预防手术引起的认知功能障碍变化，以及β-淀粉样蛋白和 τ 处理的变化。
这些数据表明，手术可以在老年患者中引发星形胶质细胞增生、β-淀粉样蛋白积累和 τ 磷酸化，这可能与术后认知功能障碍中观察到的认知下降有关。
