氧化苦参碱对N-甲基-N'-硝基-N-亚硝基胍诱导的大鼠胃肠道癌的化学预防作用：大鼠实验

[Chemopreventive effect of oxymatrine on N-methyl-N'-nitro-N-nitrosoguanidine induced gastrointestinal cancer: experiment with rats].

作者信息

Xu Qi, Jin Xi-feng, Ran Zhi-hua, Yang Chuan-hua, Xiao Shu-dong

机构信息

Department of Oncology, Renji Hospital, Jiaotong University, Shanghai 200001, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2007 Mar 27;87(12):855-8.

PMID:17565874

Abstract

OBJECTIVE

To investigate the chemopreventive effect of oxymatrine on the N-methyl-N-nitro-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 1 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 of the oxymatrine treated group [(25 +/- 24)%, P < 0.05]. The apoptotic rate of tumor cell in the MNNG treated group was (11 +/- 7)%, significantly lower than that in the oxymatrine treated group [(30 +/- 16)%, P = 0.002].

CONCLUSION

Inhibiting the development and inducing the apoptosis of gastrointestinal tumor induced by MNNG, oxymatrine can be used as a chemopreventive agent against gastrointestinal tumor.

摘要

目的

探讨氧化苦参碱对N-甲基-N-硝基-N-亚硝基胍（MNNG）诱导的胃肠道癌的化学预防作用。

方法

将99只雄性Wistar大鼠随机分为四组：MNNG处理组（36只大鼠，给予MNNG喂养28周以建立胃肠道癌大鼠模型）、氧化苦参碱干预组（n = 23，给予MNNG和氧化苦参碱）、阴性对照组（20只大鼠，给予混合饲料）和氧化苦参碱对照组（20只大鼠，给予正常食物和氧化苦参碱）。28周后所有大鼠开始给予正常食物喂养4周。在实验的第28、32和40周分别处死MNNG处理组的2只大鼠，观察胃肠道肿瘤生长情况。在第44周处死所有大鼠，评估胃肠道肿瘤的存在情况。采用免疫组织化学法检测与细胞核增殖相关的抗原Ki67的表达。采用TUNEL法检测肿瘤组织中的细胞凋亡率。

结果

92只大鼠（92.93%）完成实验。MNNG处理组胃肠道肿瘤发生率为58.62%（17/29），显著高于氧化苦参碱处理组（30.43%，7/23，P < 0.05）。阴性对照组有1只大鼠发现十二指肠肿瘤，氧化苦参碱对照组未发现肿瘤。MNNG处理组肿瘤平均体积为2.56（全距49.5）cm³，显著大于氧化苦参碱处理组[0.03（全距0.009）cm³]和阴性对照组（0.5 cm³）（均P < 0.05）。MNNG处理组胃肠道黏膜溃疡和发育异常的发生率高于氧化苦参碱处理组（均P < 0.05）。MNNG处理组肿瘤组织中Ki67的表达率为（48 ± 18）%，显著高于氧化苦参碱处理组[（25 ± 24）%，P < 0.05]。MNNG处理组肿瘤细胞凋亡率为（11 ± 7）%，显著低于氧化苦参碱处理组[（30 ± 16）%，P = 0.002]。