高脂饮食及短链脂肪酸对小鼠胃黏膜的影响研究

Effects of high-fat diet and short-chain fatty acids on gastric mucosa in mice

目的为探究高脂饮食及短链脂肪酸对小鼠胃黏膜病变的影响。方法采用40只C57BL/6雄性小鼠,随机分配为5组:正常饮食组、高脂饮食组、高脂+乙酸饮食组、高脂+丙酸饮食组、高脂+丁酸饮食组,喂养16周后取胃黏膜进行免疫组化、荧光定量PCR及蛋白质印迹法检测Hippo-Yap通路核心蛋白(Lats1、Mst1、Yap1)、CDX2、CDK2、Ki-67的表达情况。结果正常饮食组、高脂+乙酸饮食组、高脂+丁酸组小鼠胃黏膜Lats1、Mst1表达较高脂饮食组、高脂+丙酸组小鼠高,且差异具有统计学意义(P <0. 05),而Yap1、CDX2、CDK2、Ki-67的表达情况正好相反且P <0. 05,余组间比较无统计学差异(P> 0. 05)。结论高脂饮食会导致小鼠胃黏膜Lats1、Mst1减少,Yap1表达增加,从而促进Hippo-Yap信号通路的失活,同时,高脂饮食还可促进小鼠胃黏膜CDX2、CDK2、Ki-67表达增加,提示高脂饮食可促进胃黏膜病变的发生、发展。在短链脂肪酸中乙酸、丁酸可干预高脂饮食对胃黏膜的损害,而丙酸则无明显干预效果,提示饮食中增加乙酸、丁酸含量对胃黏膜具有保护作用。

Objective To investigate the effects of high-fat diet and short-chain fatty acids on gastric mucosal lesions in mice.Methods Use C57 BL/6 male mice,randomly assigned to 5 groups: Normal diet group,high fat diet group,high fat + acetic acid diet group,high Lipid + propionic acid diet group,high fat + butyric acid diet group,after 16 weeks of feeding,gastric mucosa was taken for immunohistochemistry and Real-time PCR and Western Blot detection the expression of Hippo-Yap pathway core protein( Lats1,Mst1,Yap1),CDX2,CDK2,Ki-67. Results Lats1,Mst1 expression was higher in the normal diet group,high fat + acetic acid diet group,high fat + butyric acid diet group than fat diet group,high fat + propionate group,and the difference was statistically significant( P <0. 05). However,The expression of Yap1,CDX2,CDK2,and Ki-67 was reversed and P < 0. 05,There was no significant difference between the other groups( P > 0. 05). Conclusion High-fat diet can promote the inactivation of the hippo-Yap Signaling pathway and increase the expression of CDX2,CDK2 and Ki-67 in gastric mucosa of mice,suggesting that high-fat diet can promote the occurrence and development of gastric mucosal lesions. In short-chain fatty acids,acetic acid and butyric acid can interfere with the damage of gastric mucosa in high-fat diet,while propionic acid has no obvious intervention effect,suggesting that the increase of acetic acid and butyric acid content in diet can protect gastric mucosa.