木瓜乙酸乙酯萃取部位对急性胃溃疡小鼠胃黏膜中miR-423-5p、TFF1和p53表达的影响

Effect of ethyl acetate extract from Chaenomeles speciosa( sweet) Nakaion on the expression of miR-423-5p,TFF1 and p53 in acute gastric ulcer mice

目的:观察木瓜乙酸乙酯萃取部位对急性胃溃疡实验小鼠胃黏膜miR-423-5p、TFF1和p53表达的影响,在此基础上探讨其可能的机制。方法:实验小鼠随机分为正常组、模型组、木瓜乙酸乙酯萃取部位(100、200mg/kg)和奥美拉唑组(20mg/kg)组,每天给药1次,连续给药5天,处理前24小时禁食不禁水,第5日给药后1小时,胃溃疡模型组和给药组分别灌胃给予80%乙醇10ml/kg和15mg/kg阿司匹林,4小时小鼠颈椎脱臼处死,取胃,用实时定量PCR检测胃黏膜中miR-423-5p、TFF1和p53基因表达,Western blot检测胃黏膜组织中TFF1和p53蛋白表达。结果:胃溃疡模型组胃黏膜组织中miR-423-5p基因和p53基因和蛋白表达水平明显升高,TFF1基因和蛋白表达水平略有升高,但与正常组比较无显著性差异;用木瓜乙酸乙酯萃取部位(100、200mg/kg)治疗后,miR-423-5p基因和p53基因和蛋白表达水平明显降低,TFF1基因和蛋白表达水平显著升高,与胃溃疡模型组比较具有显著性差异,奥美拉唑组作用效果不明显。结论:木瓜乙酸乙酯萃取部位(100、200mg/kg)对急性胃溃疡实验小鼠胃粘膜损伤有较好的保护作用,调节miR-423-5p、TFF1及p53表达水平,抑制miR-423-5p/TFF1/p53信号通路异常激活可能是其对酒精和阿司匹林致胃溃疡损伤保护作用的重要机制之一。

Objective： To investigate the effect of ethyl acetate extract from Chaenomeles speciosa （sweet） Nakaion on the expression of miR-423- 5 p, TFF1 and p53 in acute gastric ulcer mice, and to explore its possible mechanism. Methods： the experimental mice were randomly divid- ed into control, model, ethyl acetate extract of Chaenomeles speciosa （sweet） Nakaion （100 and 200mg/kg） and omeprazole groups （20rag/ kg）. Acute gastric ulcers were generated in mice by administration of 80% ethanol containing 15mg/mL aspirin （ 10 ml/kg, i. g. ） at the 4 hour after drugs on 5th day. The mice were killed by cervical dislocation after four hours, and remove the stomach. Real-time PCR was ap- plied to detect the mRNA expressions of miPt-423-Sp, TFF1 and p53, protein expression of TFF1 and p53 in gastric mucosa were detected by western blotting. Results： the miR-423-Sp mRNA expression, p53 mRNA and protein expressions of model group significantly increased compared with the normal group （ P 〈 0.01 ）, TFF1 mRNA and protein expression levels weakly increased （ P 〉 0.05） ; After treatment with ethyl acetate extract of Chaenomeles speciosa （sweet） Nakaion （ 100 and 200mg/kg）, the miR-423-Sp mRNA expression, p53 mRNA and protein expressions significantly decreased, the expression level of TFFI mRNA and protein were significantly increased compared with the model group （P 〈 0.05 or P 〈 0.01 ）, omeprazole group had no obvious effects. Conclusion： Ethyl acetate extract of Chaenomeles speciosa （sweet） Nakaion （ 100 and 200mg/kg） had a good protective effect on gastric mucosa of acute gastric ulcer in mice, regulating miR-423-5p, TFF1 and p53 expression, inhibiting abnormal activation of the miR-423-Sp/TFF1/p53 signaling pathway might be an important mechanism of gastric ulcer induced alcohol and aspirin.