摘要目的 评价长期腹腔注射氟比洛芬酯对骨癌痛大鼠胃粘膜及肝功能的影响.方法 健康成年SD大鼠36只,体重200 ～ 250 g,采用随机数字表法分为6组(n=6):骨癌痛+生理盐水组(BCP组)、骨癌痛+氟比洛芬酯10 mg·kg-1 ·d-1组(BF10组)、骨癌痛+氟比洛芬酯25 mg·kg-1 ·d-1组(BF25组)、骨癌痛+氟比洛芬酯50 mg·kg-1 ·d-1组(BF50组)、氟比洛芬酯50 mg·kg-1 ·d-1组(F50组)和假手术+生理盐水组(S组).BCP组和S组接种肿瘤细胞前1 d(T0)、接种后3、5、7、10、14、17和21 d(T1-7)时测定机械缩足反应阈(MWT).于T7时各组腹腔注射相应剂量氟比洛芬酯或生理盐水,2次/d,间隔12 h,连续7d,随后采集腹主动脉血样,测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP)和白蛋白(ALB)水平,处死大鼠取胃及肝脏,计算胃溃疡指数(UI),光镜下观察胃组织和肝组织病理学结果.结果 与S组比较,BCP组T2-7时MWT降低(P＜0.05),其余各指标比较差异无统计学意义(P＞0.05),BF50组和F50组血清TP和ALB浓度降低,BF25组、BF50组和F50组胃组织UI升高(P＜0.05);与BCP组比较,BF50组和F50组血清TP和ALB浓度降低,BF25组、BF50组和F50组UI升高(P＜0.05);与F50组比较,BF50组各指标差异无统计学意义(P＞0.05).BF50组和F50组胃组织部分区域粘膜上皮层缺失,深部胃腺体受损并伴有炎性细胞浸润;BF25组胃粘膜完整性和连续性轻度受损;各组肝组织结构清晰,肝细胞排列整齐,未见明显异常.结论 长期腹腔注射氟比洛芬酯可呈剂量依赖性地损伤骨癌痛大鼠胃粘膜,对肝功能无明显影响.

abstractsObjective To evaluate the effects of long-term intraperitoneal flurbiprofen axetil on the gastric mucosa and liver function in rats with bone cancer pain (BCP).Methods Thirty-six healthy female Sprague Drawley rats,weighing 200-250 g,were randomly divided into 6 groups (n =6 each):BCP + normal saline group (group BCP),BCP + flurbiprofen axetil 10 mg·kg-1 ·d-1 group (group BF10),BCP + flurbiprofen axetil 25 mg· kg-1 · d-1 group (group BF25),BCP + flurbiprofen axetil 50 mg· kg-1 · d-1 group (group BF50),flurbiprofen axetil 50 mg·kg-1 ·d-1 group (group F50),and sham operation + normal saline group (group S).BCP was induced by injecting Walker 256 mammary gland cancer cells into the bone marrow of the left tibia.In BCP and S groups,paw withdrawal threshold to mechanical stimulation (MWT) was measured at 1 day before inoculation of cancer cells (T0) and 3,5,7,10,14,17 and 21 days after inoculation (T1-7).The corresponding doses of flurbiprofen axetil or normal saline were administered intraperitoneally twice a day at 12 h intervals starting from T7 for 7 consecutive days.Blood samples were obtained from the abdominal aorta to determine the levels of alanine transaminase (ALT),aspartate transaminase (AST),total protein (TP),and albumin (ALB) in serum.The rats were then sacrificed and stomach and livers were removed for microscopic examination of pathological changes.The ulcer index (UI) was calculated.Results Compared with group S,MWT was significantly decreased at T2-7,no significant changes were found in the other parameters mentioned above in BCP group,the serum levels of TP and ALB were decreased in BF50 and F50 groups,and UI was increased in BF25,BF50 and F50 groups.Compared with BCP group,the serum levels of TP and ALB were decreased in BF50 and F50 groups,and UI was increased in BF25,BF50 and F50 groups.No significant changes were found in each parameter between BF50 and F50 groups.Microscopic examination showed that the epithelium of gastric mucous membrane became defect in partial region of the stomach and showed damage to gastric glands in the deep part and massive inflammatory cell infiltration in BF50 and F50 groups.Microscopic examination showed mild damage to the integrity and continuity of gastric mucosa and did not show any abnormality in livers in BF25 group.Conclusion Long-term intraperitoneal flurbiprofen axetil can cause damage to the gastric mucosa dose-dependently and has no effect on liver function in rats with BCP.