CAJ | 학술논문

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组):左侧后肢胫骨髓腔内注射10μl Hanks液.肿瘤组(T组):左侧后肢胫骨骨髓腔内注射10μl共4×105个Walker256大鼠乳腺癌细胞.氟比洛芬酯组(Fa组):肿瘤模型2周后从第15天开始连续腹腔注射氟比洛芬酯7d.术前1d,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±l.49)g比S组(10.92±1.04)g显著降低(P＜O.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比较明显升高,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).②S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.
목적 관찰중복주사불비락분지재골암통대서모형중진통효과급대대서간신、응혈공능적영향.방법 선택SD자성대서24지,안수궤수자표법수궤분위3조,매조8지.대조조(S조):좌측후지경골수강내주사10μl Hanks액.종류조(T조):좌측후지경골골수강내주사10μl공4×105개Walker256대서유선암세포.불비락분지조(Fa조):종류모형2주후종제15천개시련속복강주사불비락분지7d.술전1d,술후1、3、5、7、10、14、15、17、19、21、24 d검측대서족저궤계축족역치(paw withdrawal mechanical threshold,PWMT),우접충종류세포후제24천경복주동맥취혈측정간신공능、혈소판급출응혈시간,취간장、신장급종류측후지경골,HE염색관찰간신조직적형태결구급경골내종류적생장.결과 ①접충종류세포후제5천,T조대서PWMT(9.01±l.49)g비S조(10.92±1.04)g현저강저(P＜O.05;종류대서적통행위수시간축점가중,도제14천체고봉.접충후제17천개시,Fa조대서PWMT(6.64±1.70)g여T조(4.06±1.69)g비교명현승고,차이유통계학의의(P＜0.05).Fa조지속승고,지제21천시PWMT(8.04±0.81)g,단미능회복도가수술조수평(10.31±1.35) g(P＜0.05).②S조、T조급Fa조3조적응혈매원시간(prothrombin time,PT)、활화부분응혈활매시간(activated partial prothrombin time,APTT)、응혈매시간(thrombin time,TT)、섬유단백원(fibrinogen,FIB),혈소판(platelet,PLT)급간신공능검측지표,곡병전안매(glutamic-pyruvic transaminase,ALT)、곡초전안매(aspartate amino-transaminase,AST)、총단백질(total protein,TP)、뇨소(urea,UREA)、기안산항(creatinine,CREA)간차이무통계학의의.③간장、신장조직절편발현Fa조여T조병리개변무차이.T조화Fa조경골골수강내가견종류세포적생장.결론 복강주사불비락분지능현저개선골암통대서적통행위.대대서적간신공능급응혈공능무영향.
Objective To investigate the effects of repeated injection of flurbiprofen axetil on pain behaviors and side effects in a rat model of bone cancer pain.Methods 24 female SD rats were randomly divided into 3 groups(n=8) as follows.Sham group (S group): intra-tibial injection of 10 μl Hank's solution.Tumor group (T group): intra-tibial injection of 10 μl 4×105 Walker 256 mammary gland carcinoma cells.Flurbiprofen axetil group (Fa group): 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.