Parecoxib improves the cognitive function of POCD rats via attenuating COX-2

Y.-B. Wang, Z. Chen, J. Li, J. Shi

Department of Anesthesiology, Ningbo Sixth Hospital Zhejiang, Ningbo, China. lanyux@163.com

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• Pharmacology

OBJECTIVE: This study aims to explore the role of parecoxib in improving postoperative cognitive dysfunction (POCD) in rats, and to investigate the possible underlying mechanism.
MATERIALS AND METHODS: 60 Sprague Dawley (SD) rats were randomly divided into the control group (n=20), the model group (n=20), and the para group (n=20). The Morris water maze test was conducted to detect the postoperative cognitive ability of rats. The hematoxylin-eosin (HE) staining was applied to observe the neuronal density in the hippocampus of rats. The TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect the hippocampal apoptosis in rats. Meanwhile, relative levels of inflammatory factors in rat hippocampus were detected by enzyme-linked immunosorbent assay (ELISA), including interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2). Furthermore, Western blot was conducted to detect the protein levels of cyclooxygenase-2 (COX-2), PGE2, EP1, and p-Akt in rat hippocampus.
RESULTS: Behavioral test results showed that the escape latency of rats in the para group was significantly shorter than that of the model group (p<0.05). Compared with the model group, rats in para group showed significantly longer time in target quadrant and more times across the platform, as well as higher Tn/Tn+Tf (p<0.05). In the control group, pathological changes of hippocampal neurons were slighter with rare apoptotic cells. Rats in model group showed great pathological lesions with abundant apoptotic neurons, which were markedly alleviated in the para group (p<0.05). Meanwhile, ELISA showed that the levels of IL-1β, IL-6, TNF-α, and PGE2 in the para group were remarkably lower than those of the model group (p<0.05). Expression levels of COX-2, PGE2, and EP1 in the para group were significantly lower than those of the model group (p<0.05). However, the expression level of p-Akt was significantly higher than the model group (p<0.05).
CONCLUSIONS: Parecoxib improves the cognitive function of POCD rats via inhibiting COX-2 overexpression in rat brain.

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