温郁金对饮用MNNG大鼠胃黏膜血管内皮生长因子和环氧合酶-2表达的影响

Effects of Curcumae on Expressions of Vascular Endothelial Growth Factor and Cyclooxygenase-2 in Gastric Mucosa of Rats Fed with MNNG

背景:目前国内外还很少有确切疗效的胃癌化学预防药物。我们的前期研究发现温郁金可抑制胃癌细胞SGC-7901及其裸鼠移植瘤的生长。目的:通过检测温郁金水蒸气蒸馏提取液对饮用N-甲基-N’-硝基-N-亚硝基胍(MNNG)大鼠胃黏膜血管内皮生长因子(VEGF)和环氧合酶(COX)-2表达的影响,探讨其预防肿瘤的作用机制。方法:80只雄性Wistar大鼠随机分为A、B、C、D、E组,每组16只,分别为空白组、MNNG造模组、塞来昔布组、1g/ml温郁金组和2g/ml温郁金组。除空白组外,其余4组实验前6周予10%NaCl溶液1ml每周灌胃一次。然后开始40周的实验,实验期间死亡、经病理检查证实有或无胃肿瘤的大鼠均留取胃黏膜标本,计入诱癌情况统计。完成实验的大鼠于第41周处死,取胃黏膜(已致瘤者选取致瘤部位)检测VEGF和COX-2的表达。结果:VEGF和COX-2阳性表达产物主要见于细胞质内,C、D、E组大鼠VEGF和COX-2阳性表达等级积分均显著低于B组(P<0.05),D、E组与C组比较,VEGF和COX-2阳性表达差异无统计学意义(P>0.05)。结论:温郁金水蒸气蒸馏提取液可下调饮用MNNG大鼠胃黏膜VEGF和COX-2的表达,降低胃癌发生率,具有较好的胃癌化学预防潜力。

Background： Chemopreventive drugs for gastric cancer are very few. Our preliminary study showed that radix curcumae could inhibit the growth of gastric cancer cell line SGC-7901 both in vitro and in vivo. Aims： To observe the effects of distilled extract of radix curcumae on the expressions of vascular endothelial growth factor （VEGE） and cyclooxygenase （COX）-2 in gastric mucosa of rats fed with N-methyl-N＇-nitro-N-nitrosoguanidine （MNNG）. Methods： Eighty Wistar rats were randomly divided into 5 groups （A, B, C, D and E）, and 16 rats were allocated in each group. These groups were blank control group, model group, COX-2 inhibitor （celecoxib） group, 1 g/ml and 2 g/ml distilled extract of curcumae groups, respectively. In the 4 groups （except the blank control group）, 1 ml 10% NaCl was instilled into the stomach once every week in the initial 6 weeks prior to the experiment. The whole experimental period took 40 weeks. If the rats died in 40 weeks, all the stomach samples of the rats were taken whether there were gastric cancers or not, and the number of cancerous loci were counted. All the other survived rats were sacrificed at the 41st week and the expressions of VEGF and COX-2 in the gastric mucosa （including the cancerous tissue） were tested. Results： The expression products of VEGF and COX-2 were seen mainly in cell protoplasm, and were significantly weaker in Group C, D and E than in Group B （P〈0.05）, and no significant difference was found between Group D, E and C （P〉0.05）. Conclusions： The distilled extract of curcumae can down-regulate the expressions of VEGF and COX-2 in the gastric mucosa of rats fed with MNNG and can reduce the development of gastric caner, suggesting it has the potential as a chemopreventive agent for gastric cancer.