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| Effect of Parecoxib Sodium on postoperative neuroinflammation, apoptosis and cognitive function in the old rats |
| LIU Na1 XU Yue-li2 WU Ya-qi1 PENG Jun-xu1 ZHANG Xin1 LIN Jia-xin1 REN Cong-cai1▲ |
1. Department of Anesthesiology, the Eighth Affilated Hospital， Sun Yat-Sen University
2. Department of Anesthesiology, Affiliated Shenzhen Maternal and Child Healthcare Hospital
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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.
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