| Abjective: Observing the changes of learning and memory func -tions of rats after surgery, detecting the hippocapal pathology and ultrastructur- al changes and observing the apoptosis of hippocampal cells. To explore the protective effect of the new anti-inflammatory drugs of cyclooxygenase-2 (Cyclooxygenase-2,COX-2) inhibitor on postoperative cognitive dysfunction (POCD) of rats, and establish experimental basis for further studys of the pathogenesis and treatment of POCD. Methods: 40 aged healthy male SD rats (21-23months) were randomly divided into 4 groups: simple anesthesia group (M group,n=10), anesthesia+surgery group(MS group,n=10), anesthesia+COX -2 inhibitor treatment group (MZ group, n=10), anesthesia+surgery+COX-2 inhibitor treatment group (MSZ group, n=10). MZ group and MSZ group inject the same dose of COX-2 inhibitor (Amount 0.13mg/100g) in abdominal by 1 day and 1 hour before surgery. Inject 1﹪sodium pentobarbital (Amount 0.3ml/100g) in abdominal to anesthesia rats, then below the lower the edge of left rib 0.3cm cut a 1.5cm long oblique incision to the depth of the abdominal cavity. Distract the abdominal wall muscle tissue with clamp, then raised to about 5cm long small intestine in vitro with a thumb and index finger, twist small intestine with force, then put it back the abdominal cavity, suture the peritoneum, abdominal muscles and skin at last. 6 hours, 2nd and 3rd days after surgery, to give the same dose COX-2inhibitor (Amount 0.3ml/100g) repeatly, 2 times/day. At the same time, M group、MS group give the same dose NS. The Morris water maze test for learning and memory function tests, 5 days before surgery measured by escape latency navigation test, measured by probe trial target quadrant and total swim distance away as the memory performance ratio. After 1 day, 3 days, 7 days repeat the experiment. Remove the brain of rats after 7 days, fixed-dehydration-embeded-sections. Histopathological changes were observed by both hematoxylin-eosin (HE) staining under optical microscopy. Hippocampus cell apoptosis was detected with TdT-mediated dUTP nick end labeling (TUNEL). The ultrastructure changes of the hippocampus tissue were observed by means of transmission electron microscope(TEM). Results: 1. Morris water maze tests show that T1 M group escape latency extension, compare with T0 is statistically significant (P<0.05), learning and memory ability appears decrease; T1、T2、T3 MS group escape latency extension, compare with T0 are statistically significant (P<0.05), learning and memory ability appears decrease; T2、T3 M group compare with MS group are statistically significant (P<0.05); T1 MZ group compare with M group is statistically significant (P<0.05); T1、T2、T3 MSZ group escape latency extension, compare with T0 are statistically significant (P<0.05); MZ group compare with MS group escape latency are statistically significant (P<0.05). 2. HE staining observ by light microscopy show that the hippocampal pyramidal cells dead, and the MS group is the hardest. 3. TUNEL shows that TUNEL-posi -tive nuclei observed by ligh microscopy show brown staining, nuclear condens -ation,irregular shaped or round.To calculate the number of apoptotic cells use high magnification view from each group:M group(3.2±1.0), MS group (6.1±1.1),MZ group(3.2±1.2),MSZ group (4.0±1.2).M group compare with MS grou- p the difference is statistically significant (P<0.05); MS group and MSZ group, the difference is statistically significant (P<0.05). 4. Electron microscopic show that the cell swelling, and the MS group is the hardest. To calculate the number of mitochondria: M group (22±5), MZ group (22±5), MS group (21±6), MSZ group (22±6), the number of mitochondria in each group the difference is not statist-ically significant (P> 0.05). Conclusion: 1. Water maze experiment show that MZ group compare with M group the escape latency and the distance of rats in each group to swim away from the former platform quadrant are short. MSZ group compare with MS group the escape latency and the distance of rats in each group to swim away from the former platform quadrant are short. Prompt that COX-2 inhibitor on rat learning and memory ability of POCD have therapeutic effects. 2. Light microscopy show that MZ group and MSZ group compare with M group and MS group have a smaller amount of shrinkage and dead pyramidal cells. Electronic microscopy show that MZ group and MSZ group compare with M group and MS group have a smaller amount of swelling mitochondrial. Prompt that COX-2 inhibitor controls the brain inflammation effectivly, to reduce death of hippocampal cells, improve learning and memory of POCD of rats.3. Apoptosis of the hippocampal cells show that MS group compare with M group increase significantly, MSZ group compare with MS group decrease significantly. Prompt that anesthesia and apoptosis surgery lead to apoptosis of the hippocampal cells, and apoptosis of surgery is harder, COX-2 inhibitor reduces the apoptosis of hippocampal cells, and protect learning and memory functions of POCD rats. |
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