宋宇龙,王亚亚,张世平,朱利娟,王 臻.从干预SIRT1表达探究急性应激影响糖尿病小鼠葡萄糖代谢和脂肪代谢的机制[J].,2021,(24):4623-4627 |
从干预SIRT1表达探究急性应激影响糖尿病小鼠葡萄糖代谢和脂肪代谢的机制 |
Exploring the Mechanism of Acute Stress Affecting Glucose and Fat Metabolism in Diabetic Mice from the Intervention of SIRT1 Expression |
投稿时间:2021-04-22 修订日期:2021-05-18 |
DOI:10.13241/j.cnki.pmb.2021.24.004 |
中文关键词: SIRT1 急性应激 葡萄糖代谢 脂肪分解 糖尿病 |
英文关键词: SIRT1 Acute stress Glucose metabolism Lipolysis Diabetes |
基金项目:陕西省自然科学研究基础计划项目(2014JM4181);陕西省自然科学基础研究计划(2018JM7121) |
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中文摘要: |
摘要 目的:从干预组蛋白去乙酰化酶(Sirtuin1, SIRT1)表达探究急性应激影响糖尿病小鼠葡萄糖代谢和脂肪代谢的机制。方法:以30只C57BL/6小鼠为研究对象,通过高脂饮食和链脲佐菌素腹腔注射诱导的T2DM 模型小鼠,然后随机分为对照组(正常小鼠+柠檬酸盐缓冲液灌胃)、糖尿病组(糖尿病小鼠+柠檬酸盐缓冲液注射)和SIRT1干预组(糖尿病小鼠+SRT1720的载体缓冲液灌胃)。通过血糖仪和胰岛素ELISA试剂盒分别检测小鼠空腹血糖、胰岛素水平。使用血液化学自动分析仪检测小鼠血清甘油三酯、总胆固醇、低密度脂蛋白(LDL)-胆固醇和高密度脂蛋白(HDL)-胆固醇水平。收集小鼠白色脂肪组织冲洗并称重比较。通过RT-PCR分析脂肪生成转录因子PPARγ和SREBP-1c、脂肪酸合成因子Fas和Ap2、脂肪酸分解因子Hsl的mRNA表达。通过蛋白印迹分析AMPK-SIRT1-PGC-1通路蛋白的表达。结果:糖尿病组较对照组空腹血糖、胰岛素水平升高(P<0.05),SIRT1干预组较糖尿病组空腹血糖、胰岛素水平降低(P<0.05)。糖尿病组较对照组血清甘油三酯、总胆固醇、HDL-胆固醇和LDL-胆固醇升高(P<0.05)。糖尿病组较对照组附睾、腹膜后、肠系膜和腹股沟脂肪的重量升高(P<0.05),SIRT1干预组较糖尿病组的白色脂肪重量降低(P<0.05)。SIRT1干预组较糖尿病组降低(P<0.05)。糖尿病组较对照组的血糖水平在30、60和120分钟时升高(P<0.05),SIRT1干预组较糖尿病组各时间点血糖水平降低(P<0.05)。糖尿病组较对照组PPARγ、SREBP-1c、Fas、Ap2的mRNA表达升高(P<0.05),HslmRNA降低(P<0.05),SIRT1干预组较糖尿病PPARγ、SREBP-1c、Fas、Ap2的mRNA表达升高,HslmRNA降低(P<0.05)。糖尿病组较对照磷酸化AMPK、SIRT1和PGC-1的表达降低(P<0.05),SIRT1干预组较糖尿病组磷酸化AMPK、SIRT1和PGC-1的表达升高(P<0.05)。结论:调控SIRT1高表达可激活糖尿病小鼠AMPK/PGC-1α 信号通路,同时促进脂肪分解和抑制脂肪合成而表现出抗肥胖作用。 |
英文摘要: |
ABSTRACT Objective: To explore the mechanism of acute stress affecting glucose and fat metabolism in diabetic mice from the intervention of histone deacetylase (Sirtuin1, SIRT1) expression. Methods: Thirty C57BL/6 mice were used as research objects. T2DM model mice were induced by high-fat diet and intraperitoneal injection of streptozotocin. Then they were randomly divided into control group (normal mice + citrate buffer solution gavage), diabetes group (diabetic mice + citrate buffer injection) and SIRT1 intervention group (diabetic mice + SRT1720 carrier buffer gavage). The fasting blood glucose and insulin levels of mice were detected by blood glucose meter and insulin ELISA kit respectively. An automatic blood chemistry analyzer was used to detect serum triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol levels. Collect mouse white adipose tissue for washing and weighing for comparison. The mRNA expression of lipogenic transcription factors PPARγ and SREBP-1c, fatty acid synthesis factors Fas and Ap2, fatty acid decomposition factor Hsl was analyzed by RT-PCR. The expression of AMPK-SIRT1-PGC-1 pathway protein was analyzed by Western blot. Results: Compared with the control group, the diabetes group had higher fasting blood glucose and insulin levels(P<0.05), and the SIRT1 intervention group had lower fasting blood glucose and insulin levels than the diabetes group(P<0.05). Compared with the control group, the diabetes group had higher serum triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol(P<0.05). The weight of epididymis, retroperitoneum, mesenteric and inguinal fat in the diabetic group was higher than that in the control group(P<0.05), and the weight of white fat in the SIRT1 intervention group was lower than that in the diabetic group (P<0.05). The SIRT1 intervention group was lower than the diabetes group (P<0.05). The blood glucose level of the diabetes group was higher than that of the control group at 30, 60 and 120 minutes (P<0.05), and the blood glucose level of the SIRT1 intervention group was lower than that of the diabetes group at each time point(P<0.05). Compared with the control group, the mRNA expression of PPARγ, SREBP-1c, Fas, and Ap2 in the diabetes group was increased(P<0.05), and HslmRNA was decreased (P<0.05). Compared with the control group, the mRNA expression of PPARγ, SREBP-1c, Fas, and Ap2 in the SIRT1 intervention group was higher Increased, HslmRNA decreased (P<0.05). Compared with the control group, the expression of phosphorylated AMPK, SIRT1 and PGC-1 was lower in the diabetes group(P<0.05), and the expression of phosphorylated AMPK, SIRT1 and PGC-1 in the SIRT1 intervention group was higher than that in the diabetes group(P<0.05). Conclusion: Regulating the high expression of SIRT1 can activate AMPK/PGC-1α signaling pathway in diabetic mice, and at the same time promote lipolysis and inhibit fat synthesis, thus exhibiting anti-obesity effects. |
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