帕瑞昔布钠对老年大鼠术后中枢炎症反应、凋亡及认知功能的影响

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摘要目的研究选择性环氧合酶-2（COX-2）抑制剂帕瑞昔布钠对老年大鼠术后中枢炎症反应、凋亡与学习记忆功能的影响。方法选择40 只雄性老年SD 大鼠，随机分为四组（n=10）：对照组（等时间点腹腔注射给予等体积0.9% Nacl）、帕瑞昔布钠组（等时间点腹腔注射等剂量帕瑞昔布钠）、模型组（选取左肾切除术构建大鼠术后认知功能障碍模型）、治疗组[术前连续3 d 腹腔注射帕瑞昔布钠10 mg/（kg·d）+左肾切除术+术后连续3 d 给予腹腔注射帕瑞昔布钠2 mg/（kg·d），直至处死取材]。术后第3 天采用Morris 水迷宫实验评价大鼠空间学习记忆能力变化。采用Western Blot 和免疫荧光组织学方法，测定各组大鼠脑内COX-2 蛋白表达量、前列腺素E2（PGE2）含量、细胞凋亡蛋白及小胶质细胞激活状态离子钙接头蛋白分子1（Iba1）的表达量。结果术后第3 天，治疗组大鼠在目标象限停留时间[（19.06±1.45）s]长于模型组[（17.49±1.51）s]，差异有统计学意义（P＜0.05）；术后第3 天，治疗组大鼠在目标象限穿台次数[（2.45±0.82）次]多于模型组[（1.70±0.73）次]，差异有统计学意义（P＜0.05）；术后第3 天，治疗组大鼠在工作记忆测试实验中登台的潜伏期[（20.51±2.50）s]短于模型组[（22.65±2.77）s]，差异有统计学意义（P＜0.05）；术后第3 天，治疗组大鼠脑内小胶质细胞Iab1 蛋白标记阳性细胞数低于模型组，差异有统计学意义（P＜0.05）。术后第3 天，治疗组大鼠海马CA1 区COX-2/β-actin、cleaved caspase-3/caspase-3 水平及PGE2 含量低于模型组，差异有统计学意义（P＜0.05）。结论帕瑞昔布钠改善老年大鼠术后短暂性认知功能的下降，其机制与下调脑内COX-2 蛋白水平、PGE2 含量的增加以及减弱中枢神经系统炎症反应、凋亡反应等病理过程有关。

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	刘娜
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关键词 ：术后认知功能障碍, 帕瑞昔布钠, 凋亡反应, 炎症反应, 中枢神经系统

Abstract：Objective To investigate the effect of Parecoxib Sodium, a selective inhibitor of cycde-2 (COX-2), on postoperative neuroinflammation, apoptosis and cognitive function in the old rats. Methods Forty male elderly SD rats were selected and randomly divided into four groups (n=10): control group (equal volume 0.9% Nacl intraperitoneally injected at the same time point), Parecoxib Sodium group (equal dose of Parecoxib Sodium intraperitoneally injected at the same time point), model group (left nephrectomy was used to construct the model of postoperative cognitive dysfunction in rats), and treatment group, which selected Parecoxib Sodium intraperitoneally injected for 3 consecutive days preoperatively 10 mg/(kg·d) + left nephrectomy + intraperitoneal injection of Parecoxib Sodium 2 mg/(kg·d) for 3 consecutive days after the operation, until death for samples. Morris water maze test was used to evaluate the spatial learning and memory of rats on the third day after surgery. The expression levels of COX-2 protein, contents of prostaglandin E2(PGE2), expression levels of apoptosis protein and ionic calcium junction protein molecule 1 (Iba1) in activated microglia. Results On the third day after surgery, the stay time in the target quadrant of rats in the treatment group([19.06±1.45] s) was longer than that in the model group([17.49±1.51] s), and the difference was statistically significant (P ＜0.05). On the third day after surgery, the number of platform crossing in the target quadrant of rats in the treatment group ([2.45±0.82] times) was higher than that in the model group ([1.70±0.73] times), and the difference was statistically significant (P＜0.05). On the third day after surgery, the latency of stage staging in the working memory test of rats in the treatment group([20.51±2.50]s)was shorter than that in the model group([22.65±2.77]s),the difference was statistically significant (P＜0.05). On the third day after surgery, the number of Iab1 protein labeled positive cells in the brain of microglia in the treatment group was lower than that in the model group, and the difference was statistically significant (P＜0.05). On the third day after surgery, COX-2/β-actin, cleaved caspase-3/caspase-3 levels and PGE2 contents in the hippocampal CA1 region of rats in the treatment group were lower than those in the model group, and the differences were statistically significant (P＜0.05). Conclusions Treatment with Parecoxib Sodium can improve the transient cognitive function decline in elderly rats after operation, and the mechanism is related to the down-regulation of COX-2 protein level in brain, the increase of PGE2 content, and the decrease of inflammation and apoptosis in central nervous system.

Key words： Postoperative cognitive dysfunction Parecoxib Sodium Apoptosis Inflammation Central nervous system

基金资助:广东省深圳市福田区卫生公益性科研项目（FTW S2019081）。

通讯作者: 任从才（1965-），男，湖北武汉人，硕士，主任医师，麻醉科主任，主要从事临床麻醉和术后镇痛方面的研究。

作者简介: 刘娜（1979-），女，辽宁沈阳人，副主任医师，主要从事基础及临床麻醉方面的研究。

引用本文:

刘娜；徐悦利；武雅琦；彭俊旭；张欣；林嘉欣；任从才. 帕瑞昔布钠对老年大鼠术后中枢炎症反应、凋亡及认知功能的影响[J]. 中国当代医药, 2021, 28(30): 27-32.
LIU Na；XU Yue-li；WU Ya-qi； PENG Jun-xu；ZHANG Xin；LIN Jia-xin；REN Cong-cai. Effect of Parecoxib Sodium on postoperative neuroinflammation, apoptosis and cognitive function in the old rats. 中国当代医药, 2021, 28(30): 27-32.

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