高脂高果糖饮食影响大鼠衰老的机制探讨

Investigation on the mechanisms of effects of high fat and high fructose diet on rat aging

目的探讨高脂高果糖饮食对SD大鼠衰老的影响及其机制。方法成年雄性SD大鼠分为普通饮食(normal diet,ND)组和高脂高果糖(high fat and high fructose diet,HFHFD)组,干预48周后处死大鼠,取血、肝脏和脑组织。全自动生化分析仪测定血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)。酶联免疫吸附法检测血清与免疫衰老相关的细胞因子白细胞介素2(IL-2)、IL-6和晚期糖基化终末产物(AGEs)水平。采用实时荧光定量PCR和蛋白免疫印迹法检测肝和脑组织中衰老相关基因p16、p21和p53 mRNA和蛋白表达水平。结果经48周处理后,2组大鼠的体重和空腹血糖有统计学差异。HFHFD组大鼠血清TG、TC、LDL-C较ND组显著升高(P<0.05),HDL-C较ND组有增加趋势,但差异无统计学意义。与ND组相比,HFHFD组IL-2水平显著下降,IL-6和AGEs水平明显上升,差异均有统计学意义(均P<0.05)。与ND组相比,HFHFD组肝和脑组织中p16和p21 mRNA表达量均明显增加(P<0.05),p53和p21的蛋白表达量显著增加(P<0.05)。结论长期高脂高果糖饮食会加速大鼠的衰老进程,其机制可能通过损伤其免疫系统和影响肝脑组织中细胞衰老相关基因的表达有关。

Objective To investigate the mechanisms of effects of high fat and high fructose diet on rat aging.Methods Adult male SD rats were divided into normal diet(ND)group and high fat and high fructose diet(HFHFD)group.After treatment for 48 weeks,these rats were sacrificed and the blood,liver,and brain tissues were collected.Serum triglyceride(TG),total cholesterol(TC),low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C)levels were determined by automatic biochemical analyzer.The serum levels of interluekin-2(IL-2),IL-6,and advanced glycation end products(AGEs)were measured using enzyme linked immunosorbent assay.The expressions of p16,p21,and p53 genes in the liver and brain tissues were detected by real-time quantitative PCR and western blot.Results After 48 weeks treatment,there were significant differences in body weight and fasting plasma glucose between two groups.Serum TG,TC,and LDL-C in HFHFD group were significantly higher than those in the ND group(P<0.05),with an increase trend in HDL-C but without statistical difference.Compared with ND group,the level of IL-2 in HFHFD group was significantly decreased while the levels of IL-6 and AGEs were significantly increased(all P<0.05).The levels of p16 and p21 mRNA expressions as well as p53 and p21 protein expressions in liver and brain in HFHFD group were markedly increased compared with ND group(all P<0.05).Conclusion Long-term high fat and high fructose diets accelerate the aging process of rats,which may be related to the damage of the immune system and the changes of cell senescence related gene expressions in liver and brain tissues.