COX-2抑制剂对老年骨科手术患者术后谵妄的影响及其可能的作用机制

目的：观察环氧合酶-2（cyclooxygenase-2, COX-2）抑制剂对老年骨科手术患者血浆炎症因子、神经损伤相关因子和抗氧化因子水平的变化以及疼痛和谵妄评分的影响，明确COX-2抑制剂在术后谵妄（postoperative delirium, POD）防治中的作用并探究其可能的作用机制。方法：选取行择期髋关节置换手术的患者80例，随机分为帕瑞昔布钠组（P组，n=40）和对照组（C组，n=40）两组。P组患者分别于麻醉诱导前30 min和术毕各静注帕瑞昔布钠40 mg；C组相同时点静注同等容量的生理盐水。于术前1 d（T0）术前简易智能检测量表（mini-mental state examination, MMSE）评分筛查患者术前认知功能；术前1 d（T0）、术后1 d（T4）、术后3 d（T6）、术后5 d（T7）意识模糊评估法-中文修订版（CAM-CR）量表评分判断POD的发生；术前1 d（T0）、术后12 h（T3）、术后1 d（T4）、术后2 d（T5）视觉模拟评分量表（VAS）评分观测疼痛程度；于麻醉前30 min（T1）、术后1 h（T2）、术后1 d（T4）、术后3 d（T6）经颈内静脉采集中心静脉血，ELISA法测定血浆中炎症因子（IL-6和IL-10）、神经损伤相关因子（S-100β、NSE、BDNF）以及抗氧化因子（HO-1）的含量。结果：两组患者一般情况、MMSE评分及T1时点炎症因子、神经损伤相关因子、抗氧化因子均无统计学差异（P>0.05）；T2和T4时点，P组IL-6、S-100β、NSE均低于C组，IL-10、BDNF、HO-1高于C组（P<0.05）；T6时点，P组S-100β、NSE均低于C组，BDNF高于C组（P<0.05），两组IL-6、IL-10、HO-1无统计学差异（P>0.05）。两组T0时点VAS和CAM-CR评分无统计学差异（P>0.05）； T3、T4、T5时点，P组VAS评分低于C组（P<0.05）；T4、T6、T7时点，P组CAM-CR评分低于C组，P组POD发生率低于C组（P<0.05）。结论：COX-2抑制剂（帕瑞昔布钠）可减轻老年患者术后疼痛，降低术后血浆中炎症因子和神经损伤相关因子，上调抗氧化水平，降低POD发生率；其降低POD发生的机制可能与其抗炎、镇痛和抗氧化作用有关。

Effect of COX-2 inhibitors on postoperative delirium in elderly patients undergoing orthopedic surgery and its possible mechanism

AIM: To observe the effects of cyclooxygenase-2 (COX-2) inhibitors on the levels of inflammatory factors, nerve damage-related factors and antioxidant factors, as well as pain and delirium scores in the plasma of elderly patients with orthopaedic surgery, to clarify the role of COX-2 inhibitors in the prevention and treatment of POD and explore its possible mechanism. METHODS: Eighty patients undergoing elective hip arthroplasty were randomly divided into parecoxib sodium group (P group, n=40) and control group (C group, n=40). Group C was injected with the same volume of normal saline at the same time point, and the preoperative cognitive function was screened 1 d (T0) before surgery by MMSE scale. The occurrence of POD was determined by CAM-CR scale score 1 d before operation (T0), 1 d after operation (T4), 3 d after operation (T6), 5 d after operation (T7). 1 d before surgery (T0), 12 h after surgery (T3), 1 d after surgery (T4), 2 d after surgery (T5). VAS scale score was used to observe the pain degree 30 min before anesthesia (T1), 1 h after surgery (T2), 1 d after surgery (T4). Central venous blood was collected from internal jugular vein 3 days after operation (T6), and the contents of inflammatory factors (IL-6 and IL-10) nerve injury related factors (S-100β protein, NSE, BDNF) and antioxidant factors (HO-1) were determined by ELISA.RESULTS: There were no significant differences in general condition, MMSE score and inflammatory factors, nerve damage-related factors and antioxidant factors between 2 groups at T1 (P>0.05). At T2 and T4, IL-6, S-100β and NSE in group P were lower than those in group C, while IL-10, BDNF and HO-1 were higher than those in group C (P<0.05). At T6, s-100 β and NSE in group P were lower than those in group C, BDNF was higher than those in group C (P<0.05), and there were no significant differences in IL-6, IL-10 and HO-1 between the two groups (P>0.05). There were no significant differences in VAS and CAM-Cr scores between the two groups at T0 (P>0.05). VAS score of group P was lower than that of group C at T3, T4 and T5 (P<0.05). At T4, T6 and T7, the CAM-CR score of P group was lower than that of C group, and the POD incidence of P group was lower than that of C group (P<0.05). CONCLUSION: COX-2 inhibitor (Parecoxib) can relieve postoperative pain in elderly patients, reduce postoperative plasma inflammatory factors and nerve injury related factors, increase antioxidant level and reduce the incidence of POD. The mechanism of POD reduction may be related to its anti-inflammatory, analgesic and antioxidant effects.