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1.
目的:探讨选择性COX-2抑制剂尼美舒利联合顺铂对肺癌A549细胞毒性的影响及其机制.方法:应用MTT法观察尼美舒利与顺铂联合对A549细胞生长的影响,荧光显微镜以及流式细胞仪观察对A549细胞诱导凋亡的作用,免疫细胞化学SP法检测对A549细胞增殖细胞核抗原(PCAN)基因蛋白表达的影响.结果:(1)尼美舒利与顺铂联合对A549细胞的抑制率,均高于单独顺铂的抑制率(P<0.01),用金正均法判断结果表明, 二者联合对A549细胞显示协同或相加抑制作用.(2)尼美舒利与顺铂联合能介导A549细胞凋亡,二者联合组凋亡率显著高于顺铂单独作用组(P﹤0.01).(3)尼美舒利与顺铂联合组PCNA阳性细胞表达率及光密度值,显著低于单用顺铂组(P<0.01).结论:(1) 尼美舒利能协同顺铂发挥对肺癌A549的细胞毒作用;其机制可能与尼美舒利协同顺铂介导A549细胞凋亡,以及增强顺铂下调A549细胞PCNA蛋白的表达有关.(2)推测选择性COX-2抑制剂有可能成为肺癌新型的化疗辅助因子,在肺癌的综合治疗中发挥重要作用.  相似文献   

2.
环氧化酶-2在肺癌血管生成中的作用及机制   总被引:3,自引:0,他引:3  
目的 探讨环氧化酶-2 (COX- 2) 在肺癌血管生成中的作用及可能机制。方法 应用免疫组织化学法研究79例人肺癌组织COX 2、血管内皮生长因子(VEGF) 的表达; 建立裸鼠肺癌细胞株A549 移植瘤模型, 观察选择性COX- 2抑制剂尼米舒利(NIM) 对肿瘤生长的影响, 并用RT-PCR及免疫组织化学法检测裸鼠移植瘤组织的VEGF基因及蛋白表达。结果 在人肺癌组织中COX -2表达的阳性率为65. 8%, VEGF阳性率为72 .2%, COX -2 与VEGF显著相关(P<0 .01)。在裸鼠移植瘤体内实验中, NIM可有效抑制肿瘤的生长; 与对照组相比, NIM处理组肿瘤组织中VEGF mRNA及蛋白的表达均明显下调(均P<0. 01)。结论 COX -2与肺癌血管生成密切相关, 其作用机制可能是上调促血管生成因子VEGF的表达。关键词 肺癌;  环氧化酶2;  血管内皮生长因子  相似文献   

3.
4.
目的研究三氧化二砷(As_2O_3)对人肺腺癌耐顺铂细胞A549/顺铂(DDP)裸鼠移植瘤的耐药逆转作用。方法建立人肺腺癌裸鼠移植瘤模型,观察As_2O_3、DDP及联合用药对体内移植瘤生长状况的影响;采用流式细胞术(FCM)测定不同用药对肿瘤细胞凋亡率变化和耐药细胞A549/DDP P-糖蛋白(P-gp)表达;采用RT-PCR检测不同用药对A549/DDP移植瘤组织MRP1-mRNA和LRP-mRNA表达的变化。结果体内裸鼠抑瘤实验显示As_2O_3有一定抑瘤作用,联合应用DDP可显著抑制肿瘤生长。FCM结果显示应用As_2O_3后肿瘤细胞平均凋亡率,明显高于对照组(P〈0.05)[(17.204±3.091)%vs(3.436±0.537)%],低浓度As_2O_3联合DDP后肿瘤细胞的凋亡率,明显高于DDP组(P〈0.05)[(14.472±3.891)%vs(5.612±1.167)%]。FCM对P-gp表达检测提示As_2O_3对移植瘤Pgp水平无影响。RT-PCR检测结果示含As_2O_3组MRP1表达明显低于不含As_2O_3组(P〈0.05),肺癌耐药相关蛋白(LRP)在转录水平呈现相对低表达,含As_2O_3组同不含As_2O_3组间比较差异无统计学意义(P〉0.05)。结论 As_2O_3能在体内逆转A549/DDP细胞的耐药性,其机制可能是As_2O_3可通过下调MRP1基因表达,提高A549/DDP细胞对DDP敏感性逆转其耐药,并可能通过诱导肿瘤细胞凋亡来起作用。  相似文献   

5.
目的:探讨选择性CoX-2抑制剂Nimesulide对肺腺癌体内、体外的影响及其机制。方法:(1)采用MrITr比色法观察Nimesulide对肺腺癌A549细胞生长的影响,免疫细胞化学法测定肺癌A549细胞中PCNA、bcl-2基因蛋白表达水平;(2)建立肺腺癌裸鼠移植瘤模型,绘制肿瘤生长曲线并计算肿瘤抑制率。结果:(1)Nimesulide呈时间、剂量依赖性抑制A549细胞增殖,抑制率最低22.73%,最高72.04%;Nimesulide可抑制A549细胞PCNA、bcl-2的蛋白表达;(2)尼关舒利处理组的裸鼠移植瘤瘤体的平均重量为0.76±0.4g,显著低于对照组的1.56±1.02g(P〈0.05);实验结束时尼美舒利对裸鼠移植瘤的体积抑制率为41.59%,重量抑制率为51.28%。结论:Nimesulide以时间、剂量依赖性方式抑制肺癌A549细胞增殖,其机制可能与下调A549细胞Pc—NA、bcl-2的蛋白表达有关。选择性COX-2抑制剂Nimesulide有可能在肺癌防治中发挥重要作用。  相似文献   

6.
目的观察选择性环氧合酶-2(cyclooxygenase-2,COX-2)抑制剂尼美舒利对食管癌Eca-109细胞裸鼠移植瘤的抑制作用及其毒副作用,以探讨其抗肿瘤效应及可能的机制。方法培养人食管癌Eca-109细胞,建立食管癌裸鼠移植瘤模型,灌胃给予尼美舒利,观察移植瘤的生长情况,逆转录-聚合酶链反应法检测COX-2 mRNA表达,免疫组织化学技术检测COX-2及Ki-67的表达变化。结果尼美舒利对裸鼠移植瘤的生长有明显的抑制作用。尼美舒利组,尼美舒利作用4周后,移植瘤体积及瘤质量分别为(807.68±217.76)mm3及(0.81±0.21)g,较对照组的(2 116.77±362.47)mm3及(1.45±0.39)g明显减小,两组间差异有显著性(P<0.05)。两组裸鼠的体质量增加无显著性差异(P>0.05)。尼美舒利组COX-2 mRNA、蛋白及Ki-67的表达均较对照组明显减弱。结论尼美舒利对食管癌Eca-109细胞移植瘤的生长有明显抑制作用,其机制可能与抑制COX-2及Ki-67表达、抑制肿瘤细胞的生长及增殖有关。  相似文献   

7.
99mTc-MIBI检测肺癌耐药性的作用研究   总被引:3,自引:0,他引:3  
Hu S  Hu CP  Liang CH 《中华医学杂志》2005,85(21):1493-1498
目的拟探讨99mTc-MIBI能否检测肺腺癌A549DDP细胞的耐药性及人参单体Rh2作用后A549DDP细胞对顺铂耐药性的变化.方法用MTT法检测顺铂对敏感A549细胞和耐药A549DDP细胞的IC50、对A549DDP细胞的低效浓度(≤IC20),Rh2对A549DDP细胞的无毒浓度(≤IC5).以无毒浓度Rh2和低效浓度的顺铂联合作用于A549DDP细胞,检测Rh2对顺铂抑制A549DDP细胞的影响.以无毒浓度的Rh2单独作用于A549DDP细胞作为Rh2组,以低效浓度的顺铂单独作用于A549DDP细胞作为DDP组,以无毒浓度的Rh2和低效浓度的顺铂联合作用于A549DDP细胞作为Rh2+DDP组,以不加药物干预作为对照组,Hoechst33258染色荧光显微镜下观察细胞形态的变化,流式细胞仪检测细胞凋亡峰.γ计数器检测以上4组细胞及A549细胞的放射性活性.将以上细胞注入裸鼠皮下建模后,用99mTc-MIBI进行SPECT显像.结果順铂对A549细胞、A549DDP细胞的IC50分别为24、325 μmol/L,耐药指数为13.54.Rh2≤10 μmol/L时,对A549DDP细胞无明显毒性作用;100 μmol/L顺铂对A549DDP细胞的抑制率为12%.10 μmol/L Rh2与100 μmol/L顺铂联合作用,顺铂对A549DDP细胞的IC50降为94 μmol/L,与100 μmol/L顺铂单独作用于A549DDP细胞的IC50比,逆转3.5倍.荧光显微镜下,Rh2组和DDP组的大部分细胞核和对照组的一样,荧光分布均匀;Rh2+DDP组的荧光成团块分布,有凋亡小体形成.对照组、Rh2组和DDP组的细胞无明显凋亡峰,而Rh2+DDP组则出现了显著的凋亡峰.各组A549DDP细胞和A549细胞均能摄取99mTc-MIBI,Rh2组和DDP组与对照组之间细胞的放射性活性差异无统计学意义,而Rh2+DDP组则较对照组细胞的放射性活性显著性降低,P<0.05.A549细胞的放射性活性显著性高于A549DDP细胞的对照组,P<0.01.99mTc-MIBI 显像,A549组裸鼠可见瘤块的放射性浓聚影.A549DDP对照组和DDP组裸鼠亦可见瘤块的放射性浓聚影,其放射性浓度较A549组淡,这两组间的R或R′差异无统计学意义,但与A549组比较,P<0.05.DDP+Rh2组裸鼠无肿瘤生长,局部未见明显放射性浓聚影.结论 99mTc-MIBI能检测肺腺癌耐药的A549DDP细胞的耐药性;无毒浓度的Rh2能有效逆转A549DDP细胞对顺铂的耐药性,这种耐药性的变化亦能被99mTc-MIBI有效检测.  相似文献   

8.
染料木黄酮对卵巢癌HO-8910PM裸鼠移植瘤的抑制作用   总被引:3,自引:0,他引:3  
王心  辛晓燕  黄艳红 《医学争鸣》2006,27(6):536-539
目的:观察植物雌激素染料木黄酮(GEN)与顺铂(DDP)联合应用治疗人卵巢癌裸鼠移植瘤的效应及其机制.方法:建立20只人卵巢癌裸鼠移植瘤模型,随机分成4组,分别为对照组、GEN组、DDP组及GEN+DDP组.4wk后处死裸鼠,计算抑瘤率,用Ⅷ因子抗原多克隆抗体测定肿瘤内微血管密度(MVD),用细胞增殖指数(PI)反映细胞增殖状态,并进行形态学观察.结果:DDP组及GEN组均可有效抑制卵巢癌移植瘤生长,二者联合应用有协同作用.GEN+DDP组MVD和PI低于GEN组和DDP组(P〈0.01),3组均显著低于对照组(P〈0.01).形态学观察可见GEN组和GEN+DDP组细胞凋亡、凋亡小体及变性坏死增多,而对照组少见.结论:GEN对人卵巢癌HO-8910PM细胞裸鼠移植瘤有明显抑制作用,且与DDP有协同作用;GEN对肿瘤细胞的作用,与抑制肿瘤细胞的增殖和肿瘤区新生血管的生长、阻断肿瘤血供有关.  相似文献   

9.

目的  探讨西妥昔单抗联合铂类化疗对人喉鳞癌Hep-2细胞裸鼠移植瘤环氧化酶-2(COX-2)及基质金属蛋白酶-7(MMP-7)的影响。方法  选择BALB/c裸鼠24只为研究对象,均复制人喉鳞癌Hep-2细胞裸鼠移植瘤模型,随机分为西妥昔单抗组、顺铂组、西妥昔单抗联合顺铂组及对照组,各6只。对照组腹腔注射0.9%氯化钠溶液0.2 ml,西妥昔单抗组腹腔注射1 036 μg/ml西妥昔单抗注射液,顺铂组腹腔注射3μg/ml顺铂注射液,西妥昔单抗联合顺铂组腹腔注射1 036 μg/ml西妥昔单抗注射液和3 μg/ml顺铂注射液,连续4周后,脱颈处理裸鼠。比较瘤体生长情况、COX-2与MMP-7表达及信使核糖核酸(mRNA)表达。结果  西妥昔单抗组、顺铂组、西妥昔单抗联合顺铂组瘤体体积及瘤重均低于对照组(P <0.05),西妥昔单抗联合顺铂组瘤体体积、瘤重低于西妥昔单抗组与顺铂组,抑瘤率高于西妥昔单抗组及顺铂组(P <0.05);西妥昔单抗组、顺铂组、西妥昔单抗联合顺铂组裸鼠肿瘤组织COX-2、MMP-7及mRNA表达均低于对照组(P <0.05),西妥昔单抗联合顺铂组裸鼠肿瘤组织COX-2、MMP-7表达及mRNA表达低于西妥昔单抗组、顺铂组(P <0.05)。结论  西妥昔单抗联合铂类化疗有助于抑制喉鳞癌Hep-2细胞裸鼠移植瘤增殖生长,可能与抑制肿瘤组织COX-2与MMP-7表达有关。

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10.
目的 探讨贝伐单抗联合或不联合顺铂对耐顺铂肺腺癌A549/DDP移植瘤生长的抑制作用.方法 建立裸鼠移植瘤模型,随机分成空白对照组(A组)、单药贝伐单抗组(B组)、单药顺铂组(C组)、联合用药组(D组)和联合半剂量组(E组)5组,连续用药4周.观察肿瘤生长情况,计算抑瘤率;免疫组化法检测肿瘤组织微血管密度(MVD);RT-PCR分析各组经治疗后凋亡基因bcl-2及耐药基因(LRP、GST-Π)mRNA表达情况.结果 与空白对照组比较,经贝伐单抗治疗组(B、D、E组)抑瘤率分别为20.96%、51.67%、50.95%,联合用药组(D、E组)效果最佳.经贝伐单抗治疗组微血管密度分别为18.6±1.14、13.6±1.14、14.4±0.55,联合用药组最为显著,而单药顺铂组与对照组在抑瘤率和微血管密度表达上均无差异(P=0.632).经贝伐单抗治疗组bcl-2 mRNA表达较对照组有显著差异(P<0.001),但三组之间无差异(P>0.05);五组之间在LRP、GST-Π mRNA表达上无明显差异(P>0.05).结论 贝伐单抗对荷A549/DDP裸鼠移植瘤有抑制作用,联合顺铂用药有显著协同作用,同时提高A549/DDP耐药细胞对顺铂的敏感性,其作用机制可能与抑制肿瘤微血管形成、诱导细胞凋亡增加有关.  相似文献   

11.
Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

12.
Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

13.
Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P< 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P< 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.  相似文献   

14.
FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…  相似文献   

15.
目的:评价使用安心颗粒对急诊经皮冠状动脉介入术(PPCI)术后生活质量的影响.方法:将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组(术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次)和对照组(仅接受基础药物治疗).所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表(MIDAS)、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果:入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异(P>0.05);出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低(P<0.05);组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低(P<0.05).两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血(P>0.05).两组发生轻度血小板减少症的患者数比较无差异(P>0.05).结论:PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.  相似文献   

16.
Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P<0.01);the MAP decreased(P<0.01)and the HR increased drastically(P<0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.  相似文献   

17.
Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.  相似文献   

18.
Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.  相似文献   

19.
Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.  相似文献   

20.
A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care(~'4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.  相似文献   

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