国际麻醉学与复苏杂志   2012, Issue (11): 8-8
    
重复注射氟比洛芬酯对骨癌痛的影响
吴刘萍, 孙晓凤, 胡正权, 周瑜, 倪坤, 崔昕龙, 马正良, 顾小萍1()
1.徐州医学院
Effects of repeated injection of flurbiprofen axetil on a model of bone cancer pain .
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摘要:

【摘要】 目的 观察重复注射氟比洛芬酯在骨癌痛大鼠模型中镇痛效果及对大鼠肝肾、凝血功能的影响。方法 选择SD雌性大鼠24只,按随机数字表法随机分为3组,每组8只。对照组(S):左侧后肢胫骨髓腔内注射10 µl Hanks液。肿瘤组(T):左侧后肢胫骨骨髓腔内注射10 µl共4×105个Walker256大鼠乳腺癌细胞。氟比洛芬酯组(Fa):肿瘤模型2周后从第15天开始连续腹腔注射氟比洛芬酯7 d。术前1 d,术后1、3、5、7、10、14、15、17、19、21、24 d检测大鼠足底机械缩足阈值(paw withdrawal mechanical threshold,PWMT),于接种肿瘤细胞后第24天经腹主动脉取血测定肝肾功能、血小板及出凝血时间,取肝脏、肾脏及肿瘤侧后肢胫骨,HE染色观察肝肾组织的形态结构及胫骨内肿瘤的生长。结果 ① 接种肿瘤细胞后第5天,T组大鼠PWMT(9.01±1.49) g比S组(10.92±1.04) g,显著降低(P<0.05﹚;肿瘤大鼠的痛行为随时间逐渐加重,到第14天达高峰。接种后第17天开始,Fa组大鼠PWMT(6.64±1.70) g与T组(4.06±1.69) g相比明显升高,差异有统计学意义(P<0.05)。Fa组持续升高,至第21天时PWMT(8.04±0.81) g,但未能恢复到假手术组水平(10.31±1.35) g(P<0.05)。② S组、T组及Fa组3组的凝血酶原时间(prothrombin time,PT)、活化部分凝血活酶时间(activated partial prothrombin time,APTT)、凝血酶时间(thrombin time,TT)、纤维蛋白原(fibrinogen,FIB),血小板(platelet,PLT)及肝肾功能检测指标,谷丙转氨酶(glutamic-pyruvic transaminase,ALT)、谷草转氨酶(aspartate amino-transaminase,AST)、总蛋白质(total protein,TP)、尿素(urea,UREA)、肌氨酸酐(creatinine,CREA)间差异无统计学意义。③ 肝脏、肾脏组织切片发现Fa组与T组病理改变无差异。T组和Fa组胫骨骨髓腔内可见肿瘤细胞的生长。结论 腹腔注射氟比洛芬酯能显著改善骨癌痛大鼠的痛行为。对大鼠的肝肾功能及凝血功能无影响。

关键词: 氟比洛芬酯;骨癌痛;机械痛敏;副作用
Abstract:

【Abstract】 Objective To investigate the effects of repeated injection of flurbiprofen axetil on bone cancer pain and its side effects on hepatic, renal and hemostatic functions in rat. Methods 24 female SD rats were randomly divided into 3 groups (n=8) as follows. Sham group (S): intra-tibial injection of 10 µl Hank’s solution.Tumor group (T): intra-tibial injection of 10 µl 4×105 Walker256 mammary gland carcinoma cells. Flurbiprofen axetil group (Fa): intraperitoneal injection of flurbiprofen axetil on day 15 to 21 after tumor model. Paw withdrawal mechanical threshold (PWMT) was tested on day 1 before surgery and days 1,3,5,7,10,14,15,17,19,21,24 after surgery. The blood, liver, kidney and ipsilateral tibial bone of all rats were obtained on day 24 to examine the pathological changes. Results ① Compared to S group, the PWMT in T group decreased significantly at day 5 after tumor surgery [(10.92±1.04) g vs (9.01±1.49) g, P<0.05 ], and peaked at day 14 after surgery . Compared to T group, the PWMT in Fa group increased obviously at day 17 [ (6.64±1.70) g vs (4.06±1.69) g, P<0.05]. at day 21, the PWMT in Fa group was lower than that in S group [(8.04±0.81) g vs (10.31±1.35) g, P<0.05 ]. ② The results of bleeding and clotting tests[prothrombin time(PT), activated partial prothrombin time(APTT), thrombin time(TT), fibrinogen(FIB), platelet(PLT)], hepatic and renal functional tests [glutamic-pyruvic transaminase(ALT), aspartate amino-transaminase(AST), total protein(TP), urea(UREA), creatinine(CREA)] had no significant difference among S group, T group and Fa group. ③ HE staining revealed that there were no significant pathological changes in liver and renal tissue after repeated intraperitoneal injection of flurbiprofen axetil. Live tumor cells were found in tibia marrow cavities in both T and Fa groups Conclusions Repeated intraperitoneal injection of flurbiprofen axetil could significantly attenuate bone cancer pain in rats while having no influence on hepatic and renal functions as well as hemostatic function.

Key words: Flurbiprofen axetil; Bone cancer pain; Mechanical allodynia; Side effects