食源性晚期糖基化终末产物对小鼠非酒精性脂肪肝病的影响

Effect of foodborne advanced glycation end products on nonalcoholic fatty liver disease in mice

目的研究食源性晚期糖基化终产物(AGEs)对C57BL/6小鼠非酒精性脂肪肝病(NAFLD)的影响。方法选取40只12周龄雄性C57BL/6小鼠,随机分为食源性AGEs组(n=15)、外源性AGEs组(n=15)和普通饲养组(n=10)。经过24周不同饮食干预,测量小鼠体质量。采用HE染色法、油红染色法和天狼星红染色法检测小鼠肝脏的脂肪沉积和病理形态改变,采用免疫组化法检测肝脏AGEs、晚期糖基化终产物受体(RAGE)表达水平及炎症细胞因子表达水平。结果干预24周后,HE染色检测结果显示,与普通饲养组比较,外源性AGEs组和食源性AGEs组小鼠肝脏均出现了“空泡样改变”;油红染色检测结果显示,与普通饲养组比较,外源性AGEs组和食源性AGEs组小鼠肝脏脂滴明显增加(P<0.05);天狼星红色检测结果显示,与普通饲养组比较,外源性AGEs组和食源性AGEs组小鼠肝脏纤维化明显增多(P<0.05);免疫组化检测结果显示,外源性AGEs组和食源性AGEs组小鼠肝脏组织的AGEs、RAGE、白细胞介素1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)蛋白表达水平明显高于普通饲养组(P<0.05)。结论食源性AGEs能导致小鼠肝脏脂肪变性,增加小鼠肝脏RAGE的表达和炎症细胞因子的表达水平,提示食源性AGEs可能通过增加RAGE的表达并诱导炎症反应的发生,导致肝脏脂肪变性的发生与发展。

Objective To investigate the effects of foodborne AGEs on nonalcoholic fatty liver disease(NAFLD)in C57BL/6 mice.Methods 40 cases 12-week-old male C57BL/6 mice were randomly divided into foodborne AGEs group(n=15),exogenous AGEs group(n=15)and ordinary diet group(n=10).After 24 weeks of different dietary interventions,the body mass of mice was measured.HE staining,oil red staining and Sirius red staining were used to detect the lipid deposition and pathological changes of mouse liver.The expression levels of AGEs,receptor for advanced glucation end products(RAGE)and inflammatory cytokines in liver were detected by immunohistochemical method.Results After 24 weeks of intervention,HE staining showed"vacuole-like changes"in liver of mice in the exogenous AGEs group and foodborne AGEs group compared with the normal diet group.The results of oil red staining showed that liver lipid droplets in the exogenous AGEs group and foodborne AGEs group were significantly higher than those in the ordinary diet group(P<0.05).The results of Sirius red detection showed that the liver fibrosis of mice in the exogenous AGEs group and the food-derived AGEs group was significantly higher than that in the ordinary diet group.Immunohistochemical results showed that the levels of AGEs,RAGE,interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in liver tissue of mice in the exogenous AGEs group and foodborne AGEs group were significantly higher than those in the rdinary diet group(P<0.05).Conclusion Foodborne AGEs may lead to hepatic steatosis and increase the levels of inflammatory cytokines as well as the expression of RAGE in mice liver,these results suggest that dietary AGEs are involved in the pathogenesis of NAFLD possibly by activating RAGE and triggering inflammation.