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...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。展开更多
The monitoring reports of most patients with type II diabetes mellitus (T2DM) revealed that monotherapy with metformin could not achieve long-term glycemic control. Thus, we designed this study aiming to investigate t...The monitoring reports of most patients with type II diabetes mellitus (T2DM) revealed that monotherapy with metformin could not achieve long-term glycemic control. Thus, we designed this study aiming to investigate the effect of telmisartan, a unique AT1 receptor antagonist and a partial agonist of peroxisome-proliferator activated receptor gamma (PPARγ), individually and as an adjunct to metformin, on a rat model that simulates the metabolic characteristics of human T2DM. Adult male Wistar rats were fed high-fat, high-fructose diet (HFFD) for 8 weeks followed by a single low dose of streptozotocin (STZ) (35 mg/kg/day, i.p.) rendering them diabetic and insulin resistant. The effectiveness of both drugs and their combination was tested by assessing the changes in the levels of serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid profile and adiponectin. In addition, the level of reduced glutathione (GSH) in the liver, was investigated. Results showed that the addition of telmisartan to metformin successfully restored serum glucose back to normal levels and corrected the altered serum total cholesterol (TC), triglycerides (TG) and adiponectin, emphasizing the potential role of telmisartan as an adjunct to metformin.展开更多
文摘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。
文摘The monitoring reports of most patients with type II diabetes mellitus (T2DM) revealed that monotherapy with metformin could not achieve long-term glycemic control. Thus, we designed this study aiming to investigate the effect of telmisartan, a unique AT1 receptor antagonist and a partial agonist of peroxisome-proliferator activated receptor gamma (PPARγ), individually and as an adjunct to metformin, on a rat model that simulates the metabolic characteristics of human T2DM. Adult male Wistar rats were fed high-fat, high-fructose diet (HFFD) for 8 weeks followed by a single low dose of streptozotocin (STZ) (35 mg/kg/day, i.p.) rendering them diabetic and insulin resistant. The effectiveness of both drugs and their combination was tested by assessing the changes in the levels of serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid profile and adiponectin. In addition, the level of reduced glutathione (GSH) in the liver, was investigated. Results showed that the addition of telmisartan to metformin successfully restored serum glucose back to normal levels and corrected the altered serum total cholesterol (TC), triglycerides (TG) and adiponectin, emphasizing the potential role of telmisartan as an adjunct to metformin.
