特异性环氧合酶-2抑制剂西乐葆胃黏膜安全性实验研究

Experiment study on the safety of selective COX-2 inhibitor-celecoxib on gastric mucosa

目的 比较特异性环氧合酶 2 (COX 2 )抑制剂西乐葆与传统非甾体抗炎药 (NSAIDs)对胃黏膜的损害。方法 分别以西乐葆、吲哚美辛复制大鼠NSAIDs性胃黏膜损伤模型 (n =8) ;以无水乙醇复制胃黏膜急性损伤模型 ,再以西乐葆灌胃 (n =8)。观察各组胃黏膜 6 酮 前列腺素F1α(6 keto PGF1α)、血栓素B2 (TXB2 )水平、损伤指数 (LI)及光镜、扫描电镜下的变化。结果 吲哚美辛组胃黏膜损害明显 (LI :13.38± 2 .0 6 ) ,6 keto PGF1α、TXB2 明显下降 (P <0 .0 1) ,抑制率分别为 81.6 %,81.8%,LI与 6 keto PGF1α、TXB2 水平呈负相关。西乐葆组 6 keto PGF1α、TXB2 无明显抑制 (P >0 .0 5 ) ,对健康胃黏膜无损害 (LI :0 ) ,但可加重乙醇诱导的胃损伤 (LI :37.19± 3.34比 19.90± 2 .2 8,P <0 .0 1)。结论 COX 1活性抑制是NSAIDs胃病的主要机制 ;特异性COX 2抑制剂西乐葆不造成健康鼠胃黏膜损伤 ,有较高的胃肠道安全性 ,但可加重原有胃损伤。

Objective To compare the gastric mucosa damage induced by celecoxib and conventional NSAIDs——indomethacin. Methods NSAIDs induced gastric mucosal damage model in rats was obtained by pouring indomethacin, celecoxib respectively (n=8); After gastric damage induced by means of 100% ethanol, celecoxib were administered by gastric gavage (n=8). Gastric mucosal 6-keto-PGF 1α ,TXB 2 level and lesion index (LI) were measured. Morphological changes of gastric mucosa were assessed under light and scanning electronic microscopy. Results Indomethacin caused obvious gastric damage (LI:13.38±2.06) and a marked reduction of 6-keto-PGF 1α ,TXB 2 level was observed (P<0.01). Celecoxib did not produce necrotic injuries in healthy gastric mucosa (LI:0), but the injuries previously induced by ethanol worsened (LI:37.19±3.34 vs 19.90±2.28,P<0.01). Conclusions Inhibition of COX-1 is the major mechanism of NSAIDs associated gastric mucosa damage. As a selective COX-2 inhibitor, celecoxib did not produce toxic injuries on healthy gastric mucosa, thus it is safer on gastric mucosa than conventional NSAIDs. However, when administered in presence of altered gastric mucosa, it worsened gastric injuries.