摘要
目的了解氧化苦参碱对于对甲基硝基亚硝基胍(MNNG)诱导的大鼠消化道肿瘤的化学预防作用及其作用机制。方法 99只雄性 Wistar 大鼠分成4组分别服用不同的约物:阴性对照组(20只)、肿瘤模型组(36只)、氧化苦参碱干预组(23只)、氧化苦参碱对照组(20只)。给药28周后停药,正常饲料喂养至44周后观察各组大鼠的胃肠黏膜病变。并用免疫组化方法检测肿瘤模型组及氧化苦参碱干预组肿瘤组织中 Ki67的表达,用脱氧核糖核苷酸末端转移酶介导的原位缺口末端标记法(TUNEL)检测两组肿瘤组织细胞的凋亡。结果 92只(92.93%)大鼠完成实验。氧化苦参碱干预组肿瘤发生率为30.43%(7/23),明显低于肿瘤模型组[58.62%(17/29),P<0.05];阴性对照组肿瘤发生率为5%(1/20);氧化苦参碱对照组无肿瘤发生。肿瘤模型组发生肿瘤的中位体积为2.56(全距49.5)cm^3,大于氧化苦参碱干预组0.03(全距0.009)cm^3及对照组(0.5 cm^3,P<0.05)。肿瘤模型组大鼠消化道黏膜溃疡及异型增生的发生率也显著高于氧化苦参碱干预组(P<0.05)。肿瘤模型组肿瘤组织中 Ki67的表达阳性率(48±18)%显著高于氧化苦参碱干预组的肿瘤组织(25±24)%(P<0.05)。肿瘤模型组肿瘤组织细胞的凋亡率(11±7)%显著低于氧化苦参碱干预组的肿瘤组织[(30±16)%,P<0.05]。结论氧化苦参碱能通过抑制肿瘤细胞增殖,诱导其凋亡从而有效地抑制MNNG 诱导的大鼠消化道肿瘤发生。
Objective To investigate the chemopreventive effect of oxymatrine on the N-methyl-Nnitro-N-nitrosoguanidine （MNNG） -induced gastrointestinal cancer. Methods Ninety-nine male Wistar rats were randomly allocated into four groups： MNNG treated group （36 rats, fed with MNNG for 28 weeks so as to establish rat model of gastrointestinal cancer）, oxymatrine intervention group （ n = 23, fed with MNNG and oxymatrine）, negative control group （20 rats, fed with mixed feed）, and oxymatrine control group （20 rats. fed with normal food and oxymatrine）, 28 weeks later all the rats began to be fed with normal food for 4 weeks, two rats in the MNNG treated group were killed at the 28 th, 32 nd, and 40 th weeks of the experiment respectively to observe the tumor growth in the gastrointestinal tract. At the 44 th week all the rats were sacrificed and assessed for the presence of gastrointestinal tumor. Immunohistochemistry was used to detect the expression of Ki67, an antigen associated to the proliferation of nucleus. The cell apoptosis rate in the tumor tissue was detected by TUNEL method. Results Experiment was completed in 92 rats （92. 93% ）. The incidence of gastrointestinal tumor in the MNNG treated group was 58.62% （ 17/29）, significantly higher than that in the oxymatrine treated group （30.43%, 7/23, P 〈0.05 ）. Duodenum tumor was found in l rat of the negative control group and no tumor was found in the oxymatrine control group. The average volume of tumor in the MNNG treated group was 2.56（ full range 49.5 ） cm^3, significantly larger than those of the oxymatrine treated group [ 0.03 （ full range 0.009 ） cm^3 ] , and negative control group （ 0.5 cm^3 ） （both P 〈0.05 ）. The incidence rates of gastrointestinal mucosal ulceration and dysplasia of the MNNG treated group were higher than those of the oxymatrine treated group （ both P 〈 0.05 ）. The expression rate of Ki67 in the tumor tissue of the MNNG treated group was （48 ± 18）%, significantly higher than that o
出处
《中华医学杂志》
CAS
CSCD
北大核心
2007年第12期855-858,共4页
National Medical Journal of China
