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目的 评价新型非甾体抗炎药塞来昔布对胃肠道的安全性。方法 40只SD大鼠随机平均分为4组,分别以生理盐水、2%塞来昔布、0.1%消炎痛、10%西米替丁各5 ml/kg灌胃,以光镜和扫描电镜观察胃黏膜形态学改变,计算损伤指数(lesion index,LI);同时测定胃黏膜血流(gastric mucosal blood flow,GMBF),胃黏膜组织6-酮-前列腺素F1(6-keto-Prostaglandin F1α,6-keto-PGF1α)、血栓素B2(thromboxane B2,TXB2)水平。其中西咪替丁组1 h后复以0.1%消炎痛5 ml/kg灌胃,同样观察上述指标。结果消炎痛引起明显胃黏膜损害,塞来昔布则轻微。消炎痛组及西咪替丁组胃黏膜组织GMBF、6-keto-PGF1α、TXB2水平较塞来昔布组明显下降(P<0.01,P<0.05);塞来昔布组胃黏膜组织GMBF较生理盐水对照组显著下降(P<0.01),但对6-keto-PGF1α、TXB2水平无明显抑制(P>0.05)。结论 COX-2抑制剂塞来昔布对胃黏膜损伤性较小,与传统非甾体类抗炎药相比,有着较高的胃肠道安全性。
Objective To evaluate the safety of celecoxib, a new non-steroidal anti-inflammatory drug, in the gastrointestinal tract. Methods Forty Sprague-Dawley rats were randomly divided into 4 groups: normal saline, 2% celecoxib, 0.1% indomethacin and 10% cimetidine respectively. The rats were sacrificed by light microscopy and scanning electron microscopy The gastric mucosal morphology was observed and the lesion index (LI) was calculated. The gastric mucosal blood flow (GMBF) and 6-keto-prostaglandin F1α 6-keto-PGF1α) and thromboxane B2 (TXB2). Cimetidine group after 1 h with 0.1% indomethacin 5 ml / kg gavage, the same indicators were observed. Indomethacin caused significant gastric mucosal damage, while celecoxib was mild. The levels of GMBF, 6-keto-PGF1α and TXB2 in indomethacin group and cimetidine group were significantly lower than those in celecoxib group (P <0.01, P <0.05). GMBF in celecoxib group was higher than that in celecoxib group The saline control group decreased significantly (P <0.01), but had no significant inhibition on the level of 6-keto-PGF1α and TXB2 (P> 0.05). Conclusions COX-2 inhibitor celecoxib has less damage to gastric mucosa and higher gastrointestinal tract safety than traditional non-steroidal anti-inflammatory drugs.