Cao Mengya, Fang Jiakai, Wang Xueqin, Wang Yi, Duan Kaiming, Ye Feng, Ouyang Wen, Tong Jianbin
Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
Brain Res. 2018 Apr 1;1684:21-29. doi: 10.1016/j.brainres.2018.01.027. Epub 2018 Feb 3.
The upstream signal molecule modulating neuro-inflammation and synaptic changes during the pathogenesis of postoperative cognitive dysfunction (POCD) is still elusive. Here, we examined the effects and mechanisms of energy sensor AMP-activated protein kinase (AMPK) in the pathogenesis of POCD. Our data showed that surgery significantly increased the expression of p-AMPK in aged rats (p < 0.05), but not in adult rats (p > 0.05). Moreover, inhibiting AMPK activation via compound C during operation significantly improved surgery-induced impairment of the learning and memory of aged rats in water maze (p < 0.05). Further mechanism studies showed that corresponding to the impairment of learning and memory after surgery, surgery significantly increased the activation of microglia, decreased the expressions of NR2B and p-NR2B, and increased the expressions of Tau and p-Tau, which also were obviously restored by inhibiting AMPK during operation. In contrast, Inhibiting AMPK activation during operation didn't change ATP level in the hippocampus of aged rats after surgery. These data suggest that surgery induced activation of AMPK in hippocampus in an age-dependent manner. AMPK plays important roles in POCD of aged rats via multiple mechanisms, and is a possible molecular target for the prevention and treatment of POCD.
在术后认知功能障碍（POCD）发病过程中调节神经炎症和突触变化的上游信号分子仍不清楚。在此，我们研究了能量传感器AMP激活蛋白激酶（AMPK）在POCD发病机制中的作用及机制。我们的数据显示，手术显著增加了老年大鼠p-AMPK的表达（p<0.05），但对成年大鼠无显著影响（p>0.05）。此外，在手术过程中通过化合物C抑制AMPK激活可显著改善手术诱导的老年大鼠在水迷宫中学习记忆能力的损伤（p<0.05）。进一步的机制研究表明，与手术后学习记忆能力的损伤相对应，手术显著增加了小胶质细胞的激活，降低了NR2B和p-NR2B的表达，并增加了Tau和p-Tau的表达，而在手术过程中抑制AMPK可明显恢复这些变化。相比之下，手术过程中抑制AMPK激活并未改变老年大鼠术后海马体中的ATP水平。这些数据表明，手术以年龄依赖的方式诱导海马体中AMPK的激活。AMPK通过多种机制在老年大鼠的POCD中起重要作用，是预防和治疗POCD的一个可能的分子靶点。
