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肖颖馥,王能,盛文,刘露梅,孙天松,李波男,何清湖.莓茶提取物对2型糖尿病大鼠糖脂代谢及肝脏SIRT1、AMPK、PGC-1α蛋白表达的影响[J].湖南中医药大学学报英文版,2023,43(5):807-813.[Click to copy
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| 莓茶提取物对2型糖尿病大鼠糖脂代谢及肝脏SIRT1、AMPK、PGC-1α蛋白表达的影响 |
| 肖颖馥,王能,盛文,刘露梅,孙天松,李波男,何清湖 |
| (湖南中医药大学中医学院, 湖南 长沙 410208;湖南中医药大学男科实验室, 湖南 长沙 410208;湖南中医药大学中西医结合学院, 湖南 长沙 410208;湖南中医药大学中医学院, 湖南 长沙 410208;湖南医药学院, 湖南 怀化 418000) |
| 摘要: |
| 目的 探索莓茶提取物对2型糖尿病(type 2 diabetes mellitus, T2DM)大鼠糖脂代谢及肝脏沉默信息调节因子1(silence information regulator 1, SIRT1)、AMP活化蛋白激酶(AMP activated protein kinase, AMPK)、过氧化物酶体增殖物激活受体γ辅助活化因子1α(peroxisome proliferator-activated receptor-γ coactivator-1α, PGC-1α)蛋白表达的影响。方法 高脂高糖喂养联合链脲佐菌素(35 mg/kg)腹腔注射建立T2DM大鼠模型,建模成功后随机分为模型组、莓茶低剂量组(0.4 g/kg)、莓茶高剂量组(0.8 g/kg),另设普通饲料喂养大鼠为正常组,每组8只。各组灌胃给药6周后,行口服葡萄糖耐量试验计算血糖-时间曲线下面积(area under the curve, AUC),ELISA法检测空腹血胰岛素(fasting insulin, FINS)水平,计算稳态模型以评估胰岛素抵抗指数(homeostatic model assessment for insulin resistance, HOMA-IR),全自动生化分析仪测定血清总胆固醇(total cholesterol, TC)、甘油三酯(triglycerides, TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)、超氧化物歧化酶(superoxide dismutase, SOD)、丙二醇(malondialdehyde, MDA)水平,HE染色观察肝脏组织形态学变化,Western blot检测肝脏SIRT1、AMPK、PGC-1α蛋白表达。结果 与正常组比较,模型组FBG、AUC、FINS、HOMA-IR、TC、TG、LDL-C、MDA均明显升高(P<0.01),HDL-C、SOD和SIRT1、AMPK、PGC-1α蛋白表达均明显降低(P<0.01),肝脏组织肝索排列紊乱,肝细胞间隙不清晰,呈脂肪变性改变。与模型组比较,莓茶低剂量组、莓茶高剂量组FBG、FINS、HOMA-IR、TG、MDA均明显降低(P<0.05,P<0.01),SOD和SIRT1、AMPK、PGC-1α蛋白表达均明显升高(P<0.05,P<0.01),肝脏组织肝索排列相对整齐,脂肪变性得到改善;莓茶高剂量组AUC、TC均明显降低(P<0.05),HDL-C明显升高(P<0.05)。与莓茶低剂量组比较,莓茶高剂量组FBG、AUC、FINS、TC、MDA均明显降低(P<0.05),SIRT1、AMPK、PGC-1α蛋白表达均明显升高(P<0.05)。结论 莓茶提取物能在一定程度上改善T2DM大鼠糖脂代谢,减轻胰岛素抵抗,其机制可能与改善氧化应激,调节肝脏SIRT1、AMPK、PGC-1α蛋白表达有关。 |
| 关键词: 2型糖尿病 莓茶提取物 氧化应激 沉默信息调节因子1 AMP活化蛋白激酶 |
| DOI：10.3969/j.issn.1674-070X.2023.05.008 |
| Received:November 28, 2022 |
| 基金项目:全国中医药高等教育“十四五”规划教育科研课题（ZD-20-11）；湖南中医药大学研究生创新课题项目（2021CX07）；湖南中医药大学-湖南中和大汉健康产业运营管理有限公司联合基金项目（院发〔2022〕14号）。 |
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| Effects of ampelopsis grossedentata extract on glycolipid metabolism and SIRT1, AMPK and PGC-1α expressions of liver in type 2 diabetes mellitus rats |
| XIAO Yingfu,WANG Neng,SHENG Wen,LIU Lumei,SUN Tiansong,LI Bonan,HE Qinghu |
| (College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Laboratory of Andrology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan University of Medicine, Huaihua, Hunan 418000, China) |
| Abstract: |
| Objective To explore the effects of ampelopsis grossedentata extract on glycolipid metabolism and silence information regulator 1 (SIRT1), AMP activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) expressions of liver in type 2 diabetes mellitus (T2DM) rats. Methods T2DM rat model was established by high-fat/high-sugar diet combined with streptozotocin injection (STZ, 35 mg/kg) intraperitoneally. Then, T2DM rats were randomly divided into model group, low-dose ampelopsis grossedentata extract group (0.4 g/kg), and high-dose ampelopsis grossedentata extract group (0.8 g/kg), with 8 rats in each one. In addition, normal diet rats (n=8) were set as the normal group. After 6 weeks of gavage administration, oral glucose tolerance tests were performed to calculate the area under the curve (AUC) of glucose-time, fasting insulin (FINS) levels were measured by ELISA, and homeostatic model assessment for insulin resistance (HOMA-IR) was performed. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured by automated biochemical analyzer. The morphological changes of liver were observed by HE staining, and the protein expressions of SIRT1, AMPK and PGC-1α in liver tissues were measured by Western blot. Results Compared with normal group, fasting blood glucose (FBG), AUC, FINS, HOMA-IR, TC, TG, LDL-C and MDA levels dramatically increased in model group rats (P<0.01), the expressions of HDL-C, SOD, SIRT1, AMPK and PGC-1α decreased significantly (P<0.01), the arrangement of hepatic cord in liver tissue was disordered, the hepatic intercellular space was unclear and hepatic steatosis was exhibited. Compared with model group, FBG, FINS, HOMA-IR, TG and MDA significantly decreased in low- and high-dose ampelopsis grossedentata extract groups (P<0.05, P<0.01), while the expressions of SOD, SIRT1, AMPK and PGC-1α significantly increased (P<0.05, P<0.01), the hepatic cord arrangement was relatively neat, and hepatic steatosis was alleviated. AUC and TC in high-dose ampelopsis grossedentata extract group were significantly lower (P<0.05), while HDL-C was notably higher (P<0.05). Compared with low-dose ampelopsis grossedentata extract group, FBG, AUC, FINS, TC and MDA were significantly reduced, while the expressions of SIRT1, AMPK and PGC-1α significantly increased (P<0.05) in high-dose ampelopsis grossedentata extract group (P<0.05). Conclusion Ampelopsis grossedentata extract can improve glucolipid metabolism and alleviate insulin resistance in T2DM rats to a certain extent. The mechanism may be related to mitigating oxidative stress and regulating expressions of SIRT1, AMPK and PGC-1α in liver. |
| Key words: type 2 diabetes mellitus ampelopsis grossedentata extract oxidative stress silence information regulator 1 AMP activated protein kinase |
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