论文部分内容阅读
目的 研究复方苦参注射液对乳腺癌模型大鼠生存素、血清雌二醇(E2)、细胞增殖核抗原Ki-67、抑癌基因P53及程序细胞死亡因子4(PDCD4)影响.方法 除了正常组外,其余大鼠单次腹腔注射50 mg·kg-甲基亚硝基脲诱导乳腺癌发生,建立乳腺癌大鼠模型.造模成功大鼠按照体重随机分为5组,每组15只:对照组,模型组和高、中、低3个剂量实验组;从造模成功第2天开始,3个剂量实验组分别腹腔注射复方苦参注射液20,40,60 mL·kg-1;对照组灌胃三苯氧胺混悬液40mL· kg-1;模型组和正常组大鼠灌胃0.9％ NaCl 4 mL·kg-1.均1天1次,干预9周.干预后,用放射免疫测定法测定血清E2;酶联免疫吸附法法测定大鼠乳腺组织内增殖核抗原Ki-67、抑癌基因P53、磷酸化Akt、PDCD4及生存素和血清PDCD4水平.结果 给药后,正常组、模型组和低、中、高3个剂量实验组和对照组的E2水平(ng· L-1)分别为37.54±5.54,69.52±8.58,65.33±7.21,41.08±5.87,42.94±6.06和49.27±6.73;生存素水平(ng· L-1)分别为6.13±0.84,62.18±8.42,29.68±3.39,16.76±2.73,16.17±1.27和59.85±7.48;这6组的增殖核抗原Ki-67水平(ng· L-1)分别为16.20±2.14,71.28±10.87,68.88±8.62,21.54±3.17,23.75±3.17和38.63 ±5.72这6组的P53水平(ng·L-1)分别为10.86±1.13,49.17±6.48,45.13±5.17,12.18±1.75,13.17±1.36和27.44±3.52这6组的磷酸化Akt水平(ng·L-1)分别为17.12 ±4.12,37.53±5.71,23.21 ±1.86,21.56±5.21,19.32±3.21和23.21±1.86.这6组的PDCD4水平(ng·L-1)分别为22.85 ±0.31,7.72±1.18,8.83±1.18,19.29±2.74,20.06±2.25和14.83 ±6.28.与模型组比较,中、高2个剂量实验组与对照组的上述指标差异均有统计学意义(均P ＜0.05);与对照组相比,中、高2个剂量实验组的上述指标差异均有统计学意义(均P＜0.05).结论 中、高2个剂量复方苦参注射液能够明显降低乳腺癌模型大鼠Ki-67、生存率、E2、抑癌基因P53及PDCD4水平.“,”Objective To investigate the effect of Compound Matrine Injection(CMI) on the levels of nuclcar-associated antigen Ki-67,survivin,serum estradiol (E2),P53 tumor suppressor gene and programmed cell death 4 (PDCD4) in model rats of breast cancer.Methods Ninety male SD rats were selected,of them 15 rats were randomly selected as normal group.The rest of the 75 rats were used for breast cancer model construction by methyl-nitroso-urea intraperitoneal injection.Model rats that successfully established were randomly divided into five groups,15 rats in each group:control group (tamoxifen mixture 40 mL· kg-1 by gavage),the model group,high,middle and low dose experimental groups (20,40,60 mL · kg-1 CMI by intraperitoneal injection,respectively).After 9 weeks of drug interference,the serum level of E2 was determined by radioimmunoassay.The levels of Ki-67,P53,phosphorylation AKT and PDCD4,survivin in serum were determined by ELISA.Results After administration,levels of E2 (ng · L-1) were 37.54 ±5.54,69.52 ±8.58,65.33 ±7.21,41.08 ±5.87,42.94 ±6.06 and 49.27 ±6.73 in normal,model,three dose experimental and control groups,respectively.The levels of survivin (ng · L-1) in each groups were 6.13 ±0.84,62.18 ±8.42,29.68 ±3.39,16.76 ±2.73,16.17 ± 1.27 and 59.85 ±7.48,respectively.The levels of Ki-67 (ng · L-1) in above six groups were 16.20±2.14,71.28 ± 10.87,68.88 ± 8.62,21.54 ± 3.17,23.75 ±3.17 and 38.63 ±5.72,respectively.The levels of P53 (ng · L-1) in above six groups were 10.86 ± 1.13,49.17 ± 6.48,45.13 ± 5.17,12.18 ± 1.75,13.17 ± 1.36 and 27.44 ± 3.52,respectively;phosphorylation AKT (ng· L-1) in above six groups were 17.12 ±4.12,37.53 ±5.71,23.21 ± 1.86,21.56 ±5.21,19.32 ±3.21,23.21 ±1.86,respectively.The levels of serum PDCD4 (ng · L-1) in above six groups were 22.85 ± 0.31,7.72 ± 1.18,8.83 ± 1.18,19.29 ± 2.74,20.06 ± 2.25 and 14.83 ± 6.28,respectively;compared with model group,the levels of the indecators in normal,model,high,middle dose experimental and control groups had significantly(all P ＜ 0.05);compared with control group,high and middle dose experimental groups significantly (all P ＜ 0.05).Conclusion Middle and high dose of CMI could obviously decrease the levels of Ki-67,surviving,E2,P53 and PD-CD4 in the model rats of breast cancer.