铁皮石斛提取物调节内源性代谢产物S1P及相关基因预防胃癌的机制研究

发布时间：2018-04-20 06:07

本文选题：铁皮石斛提取物 + 血浆代谢组学　；参考：《中华中医药杂志》2017年05期

【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(P0.05,P0.01),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。
[Abstract]:Aim: to elucidate the mechanism of DOEs in preventing precancerous lesions by regulating endogenous metabolites and related genes based on plasma metabonomics. Methods: rats were randomly divided into 4 groups: normal group, model group, 12 脳 10-3g/kg group with low DOE and high dose of 4. 8 ~ 9. 6 g / kg. The model was established by intragastric administration of N- methyl-N- nitro-N- nitro-N- nitrosoguanidine (MNNG-0.2g / kg) every 10 days (9 times). The rats in each group were treated with 0.9% sodium chloride solution of equal volume every day, and the endogenous metabolites were analyzed by plasma metabolomics. Real-time fluorescence quantitative PCR(Real-time PCR further confirmed the correlation of endogenous metabolites. Results: compared with the model group, DOE analysis showed that the normal group, the model group, the positive drug group and the high dose group of DOE were significantly separated. Five endogenous metabolites were obtained by plasma metabolomics analysis, which were Sphingosine-1-phosphateCortexoloneone 3R-hydroxy-butanoic acididine (Niacinamideus 1415-epoxyeicosatriosenoic). Among them, S 1 P significantly decreased after treatment, compared with the model group, the difference was statistically significant. Furthermore, RT-PCR was used to detect the expression of S1P-related gene SPHK2P1PR1. Compared with the model group, the high dose of Dendrobium candidum extract could significantly reduce the expression of VEGFN SPHK1S1PR1 mRNA, but the expression of SPHK2 mRNA was not regulated in each group. Conclusion the expression of S1P and the gene expression of S1PR1 in VEGFU SPHK1P1PR1 can be decreased by WDOE, and the angiogenesis can be inhibited, thus preventing the occurrence of gastric cancer.
【作者单位】：江西中医药大学中医基础理论分化发展研究中心江西省中医病因生物学重点实验室;
【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)~~
【分类号】：R285.5

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