氟比洛芬酯用于大鼠肠道术后镇痛与肠道安全性的研究  

STUDY OF FLURBIPROFEN AXETIL ON PAIN RELIEF AND INTESTINAL SAFETY AFTER COLON SURGERY IN RATS

作　　者：孙晓晨[1] 马晓冉[1] 鞠辉[1] 冯艺[1] SUN Xiao-Chen MA Xiao-Ran JU Hui FENG Yi(Department of Anesthesiology, Peking University People＇s Hospital, Beijing 100044, China)

机构地区：[1]北京大学人民医院麻醉科,北京100044

出　　处：《中国疼痛医学杂志》2017年第9期656-661,共6页Chinese Journal of Pain Medicine

基　　金：吴阶平医学基金会临床科研专项基金(2119000296)

摘　　要：目的:探究氟比洛芬酯对结肠切除吻合术后大鼠的肠功能、疼痛及吻合口愈合的影响。方法:48只6~8周龄雄性SD大鼠随机分为四组(n=12),行肠切除吻合术。从术毕起连续3日分别给予各组以下药物:脂肪乳(Z组,0.4 ml/d)、低剂量氟比洛芬酯[F1组,12.5 mg·(kg·d)^(-1)]、中剂量氟比洛芬酯[F2组,25 mg·(kg·d)^(-1)]、高剂量氟比洛芬酯[F3组,37.5 mg·(kg·d)^(-1)]。于术后12 h、24 h、36 h、48 h、60 h定时观察是否出现新鲜粪便;在术毕当日至术后第3日测定手术切口疼痛行为学变化。分别在术后第3天、第7天每组各处死6只动物,测定吻合口爆破压力,吻合部位COX-2表达(免疫组化法)及羟脯氨酸含量(碱水解法)。结果:各组术后排便恢复时间无明显差异;术毕当日至术后第3日,F1、F2、F3组大鼠对10 g von Frey纤毛刺激手术切口的阳性反应率均较脂肪乳组下降(P<0.01)。F3组大鼠在术后3天、7天的吻合口爆破压力、COX-2表达情况和羟脯氨酸含量均较Z组明显降低(P<0.05),F2组大鼠术后第7天吻合口的爆破压力较Z组明显降低、术后3天吻合组织COX-2表达较Z组明显降低(P<0.05)。结论:氟比洛芬酯可以改善大鼠肠道术后疼痛,对肠功能恢复无明显影响。高剂量的氟比洛芬酯可能增加吻合口愈合不良的风险。Objectives：To investigate the influence of flurbiprofen axetil on bowel function, pain behaviorand anastomotic healing after colon surgery. Methods： Forty-eight male SD rats （6-8 weeks） were randomlydivided into 4 groups （n =12）, and all rats underwent colon resection and anastomosis. They received intralipid （Zgroup, 0.4 ml/d）, low dose of flurbiprofen axetil （F1 group, 12.5 mg/kg/d）, moderate dose of flurbiprofen axetil（F2 group, 25 mg/kg/d）, and high dose of flurbiprofen axetil （F3 group, 37.5 mg/kg/d）, respectively, after surgeryuntil postoperative day 3 （POD 3）. Feces was observed at 12, 24, 36, 48 and 60 h after surgery. Pain behavior wasmeasured from postoperative day 0 to day 3. Six rats in each group were sacrificed on postoperative day 3 and day7, respectively. Bursting pressure, COX-2 expression （immunohistochemistry） and hydroxyproline levels （alkalinehydrolysis） of the perianastomotic tissues were measured. Results： No significant difference in postoperativerecovery of defecation were observed among groups. F1, F2, F3 groups showed a lower response frequencyto stimulation of von Frey filament （10 g） （P〈 0.01）. Compared with Z group, the bursting pressure, COX-2expression and hydroxyproline levels were lower in F3 group both on POD 3 and POD 7 （P〈 0.05）; the burstingpressure on POD 7 and COX-2 expression on POD 3 were lower in F2 （P〈 0.05）. Conclusion： Flurbiprofenaxetil relieves postoperative pain after colon surgery with no remarkable influence on bowel function. High doseflurbiprofen axetil may increase the risk of anastomotic leakage after colon surgery.

关 键 词：氟比洛芬酯 肠吻合术 肠功能 疼痛行为学 吻合口愈合 

分 类 号：R614[医药卫生—麻醉学]