帕瑞昔布钠预先给药联合右美托咪定对老年患者术后认知功能及吲哚胺2，3-双加氧酶mRNA表达的影响

Effect of parecoxib sodium pretreatment combined with dexmedetomidine on postoperative cognitive dysfunction and expression of indoleamine 2, 3 dioxygenase mRNA in the elderly patients

目的观察帕瑞昔布钠预先给药联合右美托咪定对老年患者术后认知功能及吲哚胺2，3-双加氧酶mRNA表达的影响。方法择期行股骨粗隆骨折切复内固定术和髋关节置换术患者128例，美国麻醉医师协会评分标准（ASA）Ⅱ或Ⅲ级，年龄65～80岁，体重50～76 kg，采用随机数字表法，将其分为4组（n＝32）：对照组（C组）、帕瑞昔布钠预先给药组（P组）、右美托咪定组（D组）和帕瑞昔布钠预先给药复合右美托咪定组（PD组）。PD组于麻醉诱导前15 min，静脉注射帕瑞昔布钠40 mg，同时经15 min静脉输注负荷量右美托咪定0.5 μg/kg，然后以0.5 μg/（kg·h）的速率静脉输注至术毕。于麻醉诱导前15 min（T1）、术毕（T2）、术后6 h（T3）和术后24 h（T4）时取外周静脉血样，采用酶联免疫吸附法测定血浆白细胞介素（IL）-1β和IL-6浓度，采用荧光定量聚合酶链反应法测定血浆中吲哚胺2，3-双加氧酶（IDO）mRNA的表达；采用高效液相色谱荧光法测定血浆中的色氨酸（TRP）、犬尿氨酸（KYN）浓度，计算IDO的比活性；记录术后3 d内认知功能障碍的发生情况。结果在T2～T4时，P组IL-1β浓度[（10.5±2.1）、（12.9±2.8）、（9.7±1.8） pg/ml]和IL-6浓度[（44.7±5.6）、（61.1±6.8）、（34.9±5.2） pg/ml]，D组IL-1β浓度[（11.5±2.3）、（14.6±3.2）、（10.4±2.2） pg/ml]和IL-6浓度[（46.2±6.3）、（60.8±7.3）、（36.3±4.8） pg/ml]，PD组IL-1β浓度[（8.1±1.4）、（9.5±2.1）、（7.2±1.6） pg/ml]和IL-6浓度[（32.5±5.4）、（42.4±6.5）、（25.7±5.2） pg/ml]低于C组IL-1β浓度[（16.4±3.7）、（20.2±4.8）、（15.6±3.5） pg/ml]和IL-6浓度[（63.2±7.8）、（81.5±8.2）、（50.4±6.5） pg/ml]（P＝0.000）；在T4时，P组IDO mRNA的表达[（2.011±0.612）×103]和IDO比活性[（82.75±9.32） μmol/mmol]，D组IDO mRNA的表达[（1.982±0.568）×103]和IDO比活性[（84.75±8.91） μmol/mmol]，PD组IDO mRNA的表达[（0.893±0.339）×103]和IDO比活性[（40.54±5.58） μmol/mmol]低于C组IDO mRNA的表达[（3.426±0.581）×103]和IDO比活性[（201.41±33.74） μmol/mmol]（P＝0.000）；与P和D组比较，PD组上述各指标降低明显（P＝0.000）；术后3 d内C、P、D和PD组的POCD发生率分别为59%、34%、31%和9%，与C组比较，P、D和PD组POCD发生率均降低，且PD组降低更明显（P＝0.000）；P和D组上述各指标的差异无统计学意义。结论帕瑞昔布钠预先给药联合右美托咪定可降低老年患者术后早期认知功能障碍的发生率，其机制可能与抑制炎性反应和IDO mRNA的表达及降低IDO比活性有关。

ObjectiveTo investigate the effect of parecoxib sodium pretreatment combined with dexmedetomidine on postoperative cognitive dysfunction and expression of indoleamine 2, 3 dioxygenase （IDO） mRNA in the elderly patients.MethodsSixty USA society of Anesthesiologists score standard （ASA） Ⅱ or Ⅲ patients, aged 65-80 yr, weighing 50-76 kg, undergoing elective operation on the intertrochanteric femoral fracture and hip joint, were randomly divided into 4 groups （n=32 each）using a random number table： control group （group C）, parecoxib sodium pretreatment group （group P）, dexmedetomidine group （group D）, parecoxib sodium pretreatment combined with dexmedetomidine group （group PD）. In group PD, At 15 min before induction of anaesthesia, Pareeoxib sodium 40 mg in 5 ml normal saline was injected iv, and at the same time a loading dose of dexmedetomidine 0.5 μg/kg was infused iv over 15 min, and then was infused at a rate of 0.5 μg/（kg·h） until the end of operation. In group P and D, pareeoxib sodium and dexmedetomidine were injected iv respectively, then received the equal volume of normal saline. Group C received the equal volume of normal saline. Venous blood samples were taken at 15 min before induction of anesthesia （T1）, the end of surgery （T2）, 6 h after operation （T3）and 24 h after operation （T4） for determination of plasma concentrations of interleukin （IL）-1β, IL-6 and expression of IDO mRNA and plasma concentrations of TRP and KYN, ratio activity of IDO was calculated. Early postoperative cognitive function was assessed by Montreal Cognitive Assessment.ResultsThe plasma concentrations of IL-1β [（10.5±2.1）, （12.9±2.8）, （9.7±1.8） pg/ml] and IL-6 [（44.7±5.6）, （61.1±6.8）, （34.9±5.2） pg/ml] in group P, IL-1β [（11.5±2.3）, （14.6±3.2）, （10.4±2.2） pg/ml] and IL-6 [（46.2±6.3）, （60.8±7.3）, （36.3±4.8） pg/ml] in group D, IL-1β [（8.1±1.4）, （9.5±2.1）, （7.2±1.6） pg/ml] and IL-6 [（32.5±5.4）, （42.4±6.5）, （25.7±5.2） pg/ml] in group PD were significantly lower at T2-4 than the plasma concentrations of IL-1β [（16.4±3.7）, （20.2±4.8）, （15.6±3.5） pg/ml] and IL-6 [（63.2±7.8）, （81.5±8.2）, （50.4±6.5） pg/ml] in group C （P=0.000）; expression of IDO mRNA [（2.011±0.612）×103] and ratio activity of IDO [（82.75±9.32） μmol/mmol] in group P, expression of IDO mRNA [（1.982±0.568）×103] and ratio activity of IDO [（84.75±8.91） μmol/mmol] in group D, expression of IDO mRNA [（0.893±0.339）×103] and ratio activity of IDO [（40.54±5.58） μmol/mmol] in group PD were significantly lower at T4 than expression of IDO mRNA [（3.426±0.581）×103] and ratio activity of IDO [（201.41±33.74） μmol/mmol] in group C （P=0.000）; Compared with group P and D, all the changes were decreased in group PD （P=0.000）; Incidence of early postoperative cognitive dysfunction in group C, P, D, PD respectively was 59%, 34%, 31% and 9%. Compared with group C, incidence of early postoperative cognitive dysfunction was lower in group P, D and PD. Compared with group P and D, incidence of early postoperative cognitive dysfunction was lower in group PD （P=0.000）. There were no significant difference between group P and D.ConclusionParecoxib sodium pretreatment combined with dexmedetomidine can reduce the incidence of early postoperative cognitive dysfunction in the elderly patients, the mechanism may be related to inhibiting the inflammatory reaction and expression of IDO mRNA and ratio activity of IDO.