| 汪雯,蓝天,郑芳,等.衢枳壳提取物改善2型糖尿病小鼠胰岛素抵抗的作用研究[J].浙江中医药大学学报,2022,46(9):936-944. |
| 衢枳壳提取物改善2型糖尿病小鼠胰岛素抵抗的作用研究 |
| Effect of Quzhou Aurantii Fructus Extract on Insulin Resistance in Type 2 Diabetic Mice |
| DOI：10.16466/j.issn1005-5509.2022.09.002 |
| 中文关键词: 衢枳壳 2型糖尿病 胰岛素抵抗 肝脏 脂质合成 血脂代谢 AMPK SREBP-1 |
| 英文关键词: Quzhou Aurantii Fructus type 2 diabetes mellitus insulin resistance liver lipid synthesis blood lipid metabolism AMPK SREBP-1 |
| 基金项目:国家自然科学基金项目(81903873)；衢州市科技计划竞争性分配项目(2019K34)；浙江省医药卫生科技计划项目(2020PY087) |
|
| 摘要点击次数: 1926 |
| 全文下载次数: 1059 |
| 中文摘要: |
| [目的] 研究衢枳壳(Quzhou Aurantii Fructus，QAF)提取物改善2型糖尿病(type 2 diabetes mellitus，T2DM)小鼠胰岛素抵抗的作用及其具体机制。 [方法] 以6只雄性db/m小鼠为对照组(以蒸馏水灌胃)，选取同性别T2DM db/db小鼠24只，随机均分至模型组(以蒸馏水灌胃)、二甲双胍组(以200 mg·kg-1二甲双胍灌胃)、QAF低剂量组(以100 mg·kg-1 QAF提取物灌胃)、QAF高剂量组(以300 mg·kg-1 QAF提取物灌胃)。连续灌胃10周，监测小鼠体质量、肝质量、附睾脂肪质量；检测空腹血糖(fasting blood glucose，FBG)、空腹血清胰岛素(fasting serum insulin，FINS)水平，以此计算胰岛素敏感指数(insulin sensitivity index，ISI)、胰岛素抵抗指数(insulin resistance index，HOMA-IR)；检测血清总胆固醇(total cholesterol，TC)、甘油三酯(triglyceride，TG)、游离脂肪酸(non-esterified fatty acid，NEFA)水平；检测肝组织超氧化物歧化酶(superoxide dismutase，SOD)、过氧化氢酶(catalase，CAT)、还原型谷胱甘肽(reduced glutathione，GSH)活性，检测肝脏TC、TG表达；苏木精-伊红(hematoxylin-eosin，HE)染色观察肝组织病理结构变化；实时荧光定量聚合酶链式反应(Real-time fluorescence quantitative polymerase chain reaction，Real-time qPCR)检测肝脏中脂肪合成基因固醇调节元件结合转录因子1(sterol regulatory element-binding transcription factor 1，Srebf1)、脂肪酸合酶(fatty acid synthase，Fasn)、硬酯酰辅酶A去饱和酶(stearyl-CoA desaturase 1，Scd1)、乙酰辅酶A羧化酶1(acetyl-CoA carboxylase 1，Acc1)表达；免疫印迹法检测腺苷酸活化蛋白激酶(adenosine monophosphate activated protein kinase，AMPK)、磷酸化腺苷酸活化蛋白激酶(phosphorylated adenosine monophosphate activated protein kinase，p-AMPK)、固醇调节元件结合蛋白-1(sterol regulatory element binding protein-1，SREBP-1)蛋白表达。[结果] 与模型组比较，不同剂量QAF提取物灌胃干预后，T2DM小鼠的肝质量明显下降(P＜0.05，P＜0.01)，但体质量和附睾脂肪质量变化不明显(P＞0.05)；FBG、FINS和HOMA-IR明显下降，ISI显著升高(P＜0.05，P＜0.01)；血清TC、TG、NEFA水平下降(P＜0.05，P＜0.01)；肝脏SOD、CAT、GSH活性升高(P＜0.05，P＜0.01)；肝组织脂质变性得到缓解，且TC、TG累积变少(P＜0.05，P＜0.01)。高剂量QAF提取物灌胃能使肝脏脂肪合成基因表达下降，并抑制p-AMPK和SREBP-1蛋白表达(P＜0.05，P＜0.01)。[结论] QAF提取物可以缓解T2DM小鼠胰岛素抵抗，其机制可能与抑制肝脏脂质累积密切相关。 |
| 英文摘要: |
| [Objective] To investigate the effects of Quzhou Aurantii Fructus(QAF) extract on improving insulin resistance(IR) in type 2 diabetes mellitus(T2DM) mice and its underlying mechanism. [Methods] Six male db/m mice were applied as control group (intragastric administration of distilled water)， and twenty-four T2DM db/db mice of the same sex were selected. They were randomly and equally divided into model group(intragastric administration of distilled water)， metformin group(intragastric administration of 200 mg·kg-1 metformin)， low-dose QAF group (intragastric administration of 100 mg·kg-1 QAF extract) and high-dose QAF group (intragastric administration of 300 mg·kg-1 QAF extract). After 10 weeks of intragastric administration， the body weight of mice and the weight of liver and epididymal fat were recorded; fasting blood glucose(FBG) and fasting serum insulin(FINS) were detected to calculate insulin sensitivity index(ISI) and insulin resistance index(HOMA-IR); the serum total cholesterol(TC)， triglyceride(TG) and non-esterified fatty acid(NEFA) were detected; the activities of hepatic superoxide dismutase(SOD)， catalase(CAT)， reduced glutathione(GSH) were observed and TC， TG levels in the liver tissue were detected; hematoxylin-eosin(HE) staining was utilized to observe the hepatic histopathological changes of mice; Real-time fluorescence quantitative polymerase chain reaction(Real-time qPCR) was applied to detect the mRNA expressions of fat synthesis genes sterol regulatory element-binding transcription factor 1(Srebf1)， fatty acid synthase(Fasn)， stearyl-CoA desaturase 1(Scd1)， and acetyl-CoA carboxylase 1(Acc1); Western blot was used to detect the protein expressions of adenosine monophosphate activated protein kinase(AMPK)， phosphorylated adenosine monophosphate activated protein kinase(p-AMPK) and sterol regulatory element binding protein-1(SREBP-1). [Results] Compared with model group， the liver weight of T2DM mice decreased significantly after gavage with different doses of QAF extract (P＜0.05， P＜0.01)， but the body weight and epididymal fat weight showed no obvious change; the FBG， FINS and HOMA-IR were significantly declined， and ISI was obviously elevated(P＜0.05， P＜0.01); the serum levels of TC， TG， and NEFA were lowered(P＜0.05， P＜0.01); the activities of hepatic SOD， CAT， GSH were elevated(P＜0.05， P＜0.01); the hepatic lipid degeneration was alleviated， and the accumulation of hepatic TC and TG was reduced(P＜0.05， P＜0.01). High-dose QAF extract can significantly inhibit the expressions of fat synthesis genes， and down-regulate the protein expressions of p-AMPK and SREBP-1(P＜0.05， P＜0.01). [Conclusion] QAF extract can alleviate the insulin resistance of T2DM mice， which may be closely related with its inhibition on hepatic lipid accumulation. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |