摘要
目的:基于血浆代谢组学,阐释铁皮石斛提取物(DOE)通过调节内源性代谢产物以及相关基因,预防胃癌前病变的作用机制。方法:大鼠随机分正常组、模型组、维甲酸阳性药12×10-3g/kg组,DOE低、高剂量(4.8、9.6g/kg)组,除正常组外,其余大鼠灌胃N-甲基-N-硝基-N-亚硝基胍(MNNG)0.2g/kg建立模型,每10d 1次,共9次。各组每天灌胃相应药物,正常组给予等体积0.9%氯化钠溶液,治疗3个月后处理动物,血浆代谢组学分析内源性代谢产物,实时荧光定量PCR(Real-time PCR)进一步证实内源性代谢产物的相关作用。结果:与模型组比较,DOE能够预防胃癌发生,PCA分析显示正常组、模型组、阳性药组和DOE高剂量组明显分开,血浆代谢组学分析得到5种内源性代谢产物,分别是Niacinamide,14,15-epoxyeicosatrienoic acid,Sphingosine-1-phosphate,Cortexolone,3R-hydroxy-butanoic acid。其中S1P用药后显著降低,与模型组比较差异具有统计学意义。进一步用RT-PCR测定S1P相关的基因VEGF、SPHK1、SPHK2、S1PR1的表达,得出与模型组比较铁皮石斛提取物高剂量能够明显降低VEGF、SPHK1、S1PR1 mRNA的表达(P<0.05,P<0.01),但是各组对SPHK2 mRNA的表达无调控作用。结论:DOE能够降低S1P的表达,并能降低VEGF、SPHK1、S1PR1的基因表达,抑制血管生产,从而预防胃癌发生。
Objective: Based on metabolomics, to explain the regulation effect of dendrobium extracts on endogenous metabolites S1 P and related gene expression in prevention of gastric cancer. Methods: Rats were randomly divided into normal group, model group, retinoic acid(12×10-3g/kg) group, low and high dosage groups of dendrobium extracts(4.8, 9.6g/kg). To establish the rats model of gastric cancer, the rats except for in the normal group received gavage administration with 0.2 g/kg of MNNG, once per 10 days, total for 9 times. The rats in normal group received gavage administration with normal saline(NS), and the rest groups received corresponding drugs by gavage, totally for 3 months. The endogenous metabolites in plasma were analyzed by using metabonomics method, and the relative effect of endogenous metabolites was verified by using Real-time PCR.Results: Compared with model group, the low and high dosage of dendrobium extracts could prevent the occurrence of gastric cancer. The result of PCA analysis showed that the three groups were separated obviously. There were 5 endogenous metabolites obtained by using metabonomic analysis including Niacinamide, 14,15-epoxyeicosatrienoic acid, Sphingosine-1-phosphate, Cortexolone, and 3R-hydroxy-butanoic acid. The expression of S1 P was decreased after treatment, the result with statistical significance when compared with model group.The results of RT-PCR showed that the high dosage of dendrobium extracts could decrease the expression of S1P-related genes as VEGF, SPHK1, and S1PR1, the result with statistical significance when compared with model group(P<0.05, P<0.01, P<0.05), and there was no regulation effect on expression of SPHK2 mRNA among all the groups. Conclusion: Dendrobium extracts could decrease the expression of S1 P and the expression of S1P-related genes as VEGF, SPHK1, and S1PR1, and inhibit the production of vascular to prevent the occurrence of gastric cancer.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2017年第5期1910-1914,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
江西省自然科学基金重点课题(No.20152ACB20021)
江西省落地计划项目(No.KJLD12086)
江西省研究生创新基金项目(No.YC2015-B065)~~
