目的 考察铁皮石斛提取物(DOE)对胃癌癌变的抑制作用及相关机制。方法 动物随机分为对照组,模型组,阳性药组,DOE高、低剂量组。采用大鼠ig给予甲基硝基亚硝基胍(MNNG)200 mg/kg,每10天ig 1次,持续3个月诱导胃癌癌变模型,造模同时给予DOE,对照组给予生理盐水;实验结束后HE染色分析胃组织癌变程度,计算癌变率;RT-PCR测定胃组织中表皮生长因子(EGF)、表皮生长因子受体(EGFR)、Bax、Bcl-2 mRNA表达情况;TUNEL法测定胃组织中细胞凋亡;ELISA测定血浆中EGF、EGFR的量。结果 DOE高剂量能够明显抑制胃癌癌变,与模型组比较差异显著(P<0.01);DOE能显著降低胃组织中EGF、EGFR mRNA以及血浆中EGF、EGFR的表达,与模型组比较差异显著(P<0.05、0.01);并能够明显升高Bax mRNA表达、降低Bcl-2 mRNA的表达,与模型组比较差异显著(P<0.05、0.01),TUNEL法显示其具有诱导细胞凋亡的作用。结论 DOE能够抑制大鼠胃癌癌变,其机制可能与降低组织中EGF、EGFR mRNA表达与血浆中EGF、EGFR的量有关,同时降低Bcl-2 mRNA、升高Bax mRNA表达,诱导细胞发生凋亡。

Objective To explore the inhibitory effects of Dendrobium officinale extract (DOE) on gastric carcinogenesis and its related molecular mechanism. Methods The rats were randomly divided into normal group, model group, positive drug group, low-dose and high-dose DOE groups. The gastric carcinogenesis model was induced by ig giving 200 mg/kg N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at doses of 200 mg/kg every 10 days for 3 months. Meanwhile, the rats in the treatment groups were given the corresponding doses of drug while the rats in the control group were given normal saline. At the end of the experiment, the degree of gastric tissue carcinogenesis was calculated by HE staining analysis. The expression levels of EGF, EGFR, Bax, and Bcl-2 mRNA were detected by RT-PCR test in gastric tissue. The levels of EGF and EGFR in plasma were detected by ELISA. Apoptosis was detected by TUNEL assay. Results Compared with the model group, the high-dose DOE could inhibit the degree of carcinogenesis significantly (P < 0.01). Both high-dose and low-dose DOE could significantly reduce the levels of EGF, EGFR mRNA, and Bcl-2 mRNA, and increase the levels of Bax mRNA in gastric tissue, with statistical significance compared with the model group (P < 0.05, 0.01). In addition, they also reduced the levels of EGF and EGFR in plasma significantly and induced apoptosis. Conclusion DOE could inhibit the gastric carcinogenesis, which might be related to effects of decreasing the expression of EGF and EGFR mRNA in gastric tissue and EGF and EGFR in plasma and inducing the apoptosis through reducing the expression of Bcl-2 mRNA and increasing Bax mRNA.

国家自然科学基金资助项目(81260523);江西省落地计划项目(KJLD12086);江西省自然基金项目(20152ACB20021);江西中医药大学校级课题(2014ZR001,2014ZR042)