非甾体类抗炎药相关性胃黏膜损伤情况及替普瑞酮保护作用的随机对照观察

Side effects of non-steroidal anti-inflammatory drugs on gastric mucosa and preventive effects of teprenone

目的评价长期服用非甾体类抗炎药（NSAID）引发胃黏膜的损伤情况，并探讨替普瑞酮对患者胃黏膜的保护作用。方法收集长期服用NSAID且幽门螺杆菌（Hp）阴性患者108例，进行上消化道症状及胃镜评估。其中无溃疡患者92例，采用前瞻性随机对照研究，按是否服用替普瑞酮随机分为干预组（45例）与非干预组（47例），随访3个月后再次行上消化道症状及胃镜评估。在人选时及随访3个月后分别留取胃黏膜标本比较胃黏液层密度和环氧合酶（COX）表达水平。结果在108例患者中发现消化性溃疡16例（14．8％），48例（44．4％）患者在胃镜下可观察到3处及以上黏膜糜烂灶。随访3个月后，替普瑞酮干预组患者胃黏膜损伤明显轻于非干预组（Z=－4．96，P=0．000）；胃黏液合成与分泌多于非干预组[阳性率66．7％（30／45）比13．3％（6／45），P=0．000]；COX－1表达亦多于非干预组[31．1％（14／45）比6．7％（3／45），P=0．003]；而COX-2表达则无变化[28．9％（13／45）比31．1％（14／45），P＝0．82]。结论长期服用NSAID可致明显胃黏膜损伤；同时服用替普瑞酮可以降低胃黏膜损伤的发生，这可能与其促进黏液合成分泌和增加黏膜内COX－1表达有关。

Objective To evaluate the side effects of non-steroidal anti-inflammatory drugs （NSAID） on gastric mucosa and to study the preventive effects of teprenone in patients. Methods A total of 108 patients taking NSAID for more than 3 months with no infection of Helicobacter pylori （ Hp ） were recruited. All patients were screened by endoscopy and their upper gastrointestinal symptoms were evaluated. Then, after excluding 16 patients with ulcers, 92 patients were randomly divided into intervention group with teprenone and control group. After follow-up for 3 months, the patients were re-screened by endoscopy and their upper gastrointestinal symptoms re-evaluated. Specimens of gastric mucosa were studied by PAS staining, and eyclooxygenase （COX） level were evaluated by immunohistochemical technique. Results Among the patients taking NSAIDs, erosion occurred in 48 （44. 4% ） patients while 16 （ 14. 8% ） were found with peptic ulcer. The damages improved significantly （ Z = - 4. 96, P = 0. 000 ） in the intervention group with teprenone （n = 45 ） as compared with the control group （n = 47 ） after follow-up for 3 months. Both COX-1 level [31.1% （14/45） vs 6. 7% （3/45） ,P =0. 003] and mucous thickness [66. 7% （30/45） vs 13.3% （6/45） ,P = 0. 000 ] also increased in the intervention group as compared with the control group. No significant difference was found in COX-2 level between these two groups[28. 9% （13/45）vs 31.1% （ 14/45）, P = 0. 82 ]. Conclusion Long-term use of NSAID caused severe damages to gastroduodenal mucosa; teprenone improved NSAID-related gastric side effects and increased COX-1 level and mucous thickness.