[非甾体抗炎药对大鼠COX - 1 - COX - 2的体内选择性及胃肠道溃疡]
[In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1-COX-2 and gastrointestinal ulcers, in rats].
作者信息
Laudanno O M, Cesolari J A, Esnarriaga J, Flaherty P, Vada J, Guastalli G, San Miguel P, Bedini O A
机构信息
Cátedras de Gastroenterología y de Histología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Argentina.
出版信息
Acta Gastroenterol Latinoam. 1998;28(3):249-55.
UNLABELLED
This work was aimed to study COX-1 and COX-2 selectivity in 16 non-steroidal anti-inflammatory drugs (NSAIDs), at ulcerogenic doses in 2 experimental models: 1) provided subcutaneously (sc), after solid food(SF), (antrum ulcers and intestinal erosions); and 2) orally (O) (fundic and intestinal erosions).
METHODS
17 groups of female Wistar rats (n = 7 each group), weighing 200 g, 36 h fasting with water ad libitum, were submitted to the following experiments: 1. SF (Cargill chow) during 1 h, and then sc: 1.1 ml saline; 2. diclofenac (Di); 3. indomethacine (Indo); 4. Ketorolac (Ke); 5. meloxicam (Mel); 6. Pyroxicam (P); 7. tenoxicam (T). The dose for the aforementioned drugs was 60 mg/kg; 8. aceclofenac (Ace); 9. 200 mg/kg nimesulide (Ni); 10. mefenamic acid (Mac); 11. aspirin (A); 12. etodolac (E); 13. ibuprophen (Ibu); 14. nabumetone (Na); 15. naproxene (Nap); 16. ketoprophen (Ket); 17. paracetamol (Pa), 500 mg/kg. II. The drugs where administered by orogastric tubing to the same groups of fasting animals. After 24 h the animals were killed by ether overdose. Laparotomy was performed and the stomach and the small intestine was removed. The percentage of antum ulcer, and fundic and intestinal erosion (mm2) was tabulated by planimetry. Blood and histological samples were obtained.
RESULTS
The NSAIDs Indo, Ibu, Ke, Ket, P and Te yielded an antrum ulcer area: 5-29% and intestinal erosion, 101-395 mm2, similar to Indo (p > 0.50). In contrast there were neither ulcers nor intestinal erosions with Mac, A, Di, E and Nap (p > 0.50). While there were absence of ulcers with Ace, Me, Na, Ni and Pa and slight intestinal erosion (0-23 mm2; p < 0.01). II. There were differences in the following oral (NAIDs: Ace, Me, NA, Ni and Pa, yielding 0-5% fundic erosion and 0-22 mm2 intestinal erosion (p < 0.001). The other NSADs yielded 33-90% fundic erosion and 116-550 mm2 intestinal erosion, similarly to Indo (p > 0.50).
HISTOLOGY
Leukocyte infiltrate in the gastrointestinal mucosa with all the NSADs, except Ibu and Pa. There was also neutrophilia (5000-20,000), but not with Ibu and Pa (700-1200).
CONCLUSIONS
COX-2-COX-1 selectivity was demonstrated "in vivo" in aceclofenac, meloxicam, nabumetone, nimesulide and paracetamol.
未标记
本研究旨在研究16种非甾体抗炎药（NSAIDs）在两种实验模型中致溃疡剂量下的COX - 1和COX - 2选择性：1）在固体食物（SF）后皮下注射（sc）（胃窦溃疡和肠道糜烂）；2）口服（O）（胃底和肠道糜烂）。
方法
17组雌性Wistar大鼠（每组n = 7），体重200 g，禁食36小时，自由饮水，进行以下实验：1. 1小时内给予SF（嘉吉饲料），然后皮下注射：1.1 ml生理盐水；2. 双氯芬酸（Di）；3. 吲哚美辛（Indo）；4. 酮咯酸（Ke）；5. 美洛昔康（Mel）；6. 吡罗昔康（P）；7. 替诺昔康（T）。上述药物剂量为60 mg/kg；8. 醋氯芬酸（Ace）；9. 200 mg/kg尼美舒利（Ni）；10. 甲芬那酸（Mac）；11. 阿司匹林（A）；12. 依托度酸（E）；13. 布洛芬（Ibu）；14. 萘丁美酮（Na）；15. 萘普生（Nap）；16. 酮洛芬（Ket）；17. 对乙酰氨基酚（Pa），500 mg/kg。二、通过灌胃法将药物给予同一组禁食动物。24小时后，通过过量乙醚处死动物。进行剖腹手术，取出胃和小肠。通过面积测量法将胃窦溃疡、胃底和肠道糜烂的百分比（mm²）制成表格。采集血液和组织学样本。
结果
NSAIDs中的吲哚美辛、布洛芬、酮咯酸、酮洛芬、吡罗昔康和替诺昔康产生的胃窦溃疡面积为5 - 29%，肠道糜烂面积为101 - 395 mm²，与吲哚美辛相似（p > 0.50）。相比之下，甲芬那酸、阿司匹林、双氯芬酸、依托度酸和萘普生既无溃疡也无肠道糜烂（p > 0.50）。而醋氯芬酸、美洛昔康、萘丁美酮、尼美舒利和对乙酰氨基酚无溃疡，有轻微肠道糜烂（0 - 2 mm²；p < 0.01）。二、以下口服NSAIDs存在差异：醋氯芬酸、美洛昔康、萘丁美酮、尼美舒利和对乙酰氨基酚，产生0 - 5%的胃底糜烂和0 - 22 mm²的肠道糜烂（p < 0.00）。其他NSAIDs产生33 - 90%的胃底糜烂和116 - 550 mm²的肠道糜烂，与吲哚美辛相似（p > 0.50）。
组织学
除布洛芬和对乙酰氨基酚外，所有NSAIDs均导致胃肠道黏膜白细胞浸润。也有中性粒细胞增多（5000 - 20000），但布洛芬和对乙酰氨基酚无此现象（700 - 1200）。
结论
在醋氯芬酸、美洛昔康、萘丁美酮、尼美舒利和对乙酰氨基酚中证实了“体内”COX - 2 - COX - 1选择性。
Zotero 插件