二冬膏延缓胃癌发生的作用机制

Preventive Mechanism of Erdong Gao on Gastric Cancer

目的:通过分析大鼠胃组织细胞凋亡和血浆差异代谢产物,探讨二冬膏延缓胃癌发生的作用机制。方法:大鼠随机分为正常组、模型组、维甲酸(12×10^(-3)g·kg^(-1))组、二冬膏低、高剂量(6,12 g·kg^(-1))组,除正常组外,其余大鼠ig N-甲基-N'-硝基-N-亚硝基胍(MNNG)0.2 g·kg^(-1)建立模型,10 d/次,共9次。各组每天ig相应药物,正常组ig等体积生理盐水,治疗3个月后处理动物,苏木素伊红(HE)染色分析胃癌程度及病理变化的改善;实时荧光定量PCR(Real-time PCR)测定胃组织中凋亡抑制基因B淋巴细胞瘤-2(Bcl-2)mRNA表达;脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测胃组织细胞凋亡;血浆代谢组学寻找差异代谢产物。结果:与模型组比较,二冬膏低、高剂量组病变主要在良性的乳头状瘤和乳头状增生,说明二冬膏能够改善胃癌病变程度;低剂量组能明显降低胃组织Bcl-2 mRNA的表达(P<0.01),TUNEL显示二冬膏低、高剂量组胃组织细胞凋亡数比模型组高。二冬膏低剂量血浆代谢产物中发现的鞘氨醇-1-磷酸(Sphingosine-1-phosphate),20-羟基-二十烷四烯酸(20-HETE),甘氨胆酸(Glycocholic acid)等与细胞凋亡相关。结论:二冬膏能够促进胃癌变大鼠胃组织发生细胞凋亡,延缓胃癌发生。

Objective： To study of the effect and mechanism of Erdong Gao on gastric cancer rats through the analysis on cell apoptosis and bio-marker. Method： The rats was divided into normal group,model group,retinoic acid（ 12 × 10^-3g·kg^-1） group,and low-dose and high-dose Erdong Gao（ 6,12 g·kg^-1） groups.Except for normal group,the model was made through gavage with N-methy-N＇-nitro-N-nitrosoguanidine（ MNNG）0. 2 g·kg^-1,once every 10 days,for a total of 9 times. Each group was given corresponding drugs through gavage,and the normal group was given isopyknic NS. After 3 months,rats ware sacrificed,the pathological changes were observed by hematoxylin-eosin（ HE） staining,the mRNA expression of Bcl-2 was detected by Real-time PCR,the cell apoptosis was detected by Td T-mediated d UTP nick end labeling（ TUNEL）,and the plasma metabonomics was performed to find differentiated metabolites. Result： Different does of Erdong Gao can improve the pathological changes of gastric cancer,mainly by targeting at the benign papillary hyperplasia and papilloma; low-dose Erdong Gao can significantly suppress the mRNA expression of Bcl-2（ P〈0. 01）. According to TUNEL,high and lowdose Erdong Gao groups showed a higher rate of cell apoptosis than the model group. Plasma metabolites of lowdose Erdong Gao showed Sphingosine-1-phosphate,20-hydroxyeicosatetraenoic acid（ 20-HETE）,and glycocholic acid,which were correlated with cell apoptosis. Conclusion： Erdong Gao could promote cell apoptosis in gastric cancer rats.