[关键词]
[摘要]
【目的】观察芪丹颗粒改善2型糖尿病 (T2DM) 大鼠糖脂代谢紊乱的治疗作用及机制。 【方法】将实验大鼠随机分为正常 组,模型组,芪丹低、高剂量组和芪丹高剂量+磷脂酰肌醇3-激酶 (PI3K) 抑制剂组。正常组常规喂养,其他各组大鼠采用高 糖高脂饮食喂养联合链脲佐菌素 (STZ) 注射法构建T2DM模型。将造模成功的大鼠给予对应药物干预,观察干预前后大鼠一 般情况,记录大鼠的体质量,检测空腹血糖,血脂谱[总胆固醇 (TC) 、甘油三酯 (TG) 、低密度脂蛋白胆固醇 (LDL-C) 及高密 度脂蛋白胆固醇 (HDL-C) ]及空腹胰岛素值,计算稳态模型评估的胰岛素抵抗指数 (HOMA-IR) ,采用实时定量聚合酶链反应 (qRT-PCR) 法检测肝脏组织中PI3K、蛋白激酶B (AKT) 、糖原合酶激酶3β (GSK3β) 的mRNA表达水平,采用Western Blot法 检测肝脏组织中PI3K、AKT、GSK3β的蛋白表达水平。 【结果】与模型组比较,芪丹颗粒高剂量组大鼠体质量降低,空腹血 糖值降低,TC、TG、LDL-C水平降低,HDL-C升高,HOMA-IR值降低,肝脏组织PI3K、AKT、GSK3β mRNA表达量升高, 肝脏组织p-PI3K、p-AKT、p-GSK3β的相对表达量升高,差异均有统计学意义 (P<0.05) ;芪丹颗粒低剂量组和芪丹颗粒高剂 量+PI3K抑制剂组对上述指标的改善程度较芪丹颗粒高剂量组均有所下降。 【结论】芪丹颗粒可减轻T2DM大鼠的体质量,改 善糖脂代谢及胰岛素抵抗水平,其作用机制可能与激活PI3K/AKT/GSK3β信号通路有关。
[Key word]
[Abstract]
Objective To investigate the therapeutic effects and mechanism of Qidan Granules (QDG) on glucose and lipid metabolism disorders in type 2 diabetes mellitus (T2DM) . Methods Rats were randomly divided into normal group, model group, QDG low-dose group, QDG high-dose group, and QDG high-dose + PI3K inhibitor group. The normal group received standard chow,while other groups were fed a high-fat/high-sugar diet and injected with streptozotocin (STZ) to establish T2DM. After modeling,rats received corresponding treatments. General conditions were monitored,with body mass,fasting blood glucose (FBG) ,lipid profiles [total cholesterol (TC),triglycerides (TG),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C) ],and fasting insulin levels recorded. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Hepatic mRNA expression of PI3K,AKT,and GSK3β was quantified via qRT-PCR,while protein levels of PI3K,AKT,GSK3β were measured by Western Blot. Results Compared with the model group, the QDG high-dose group showed reduced body mass (P<0.05) ,reduced FBG (P<0.05) ,decreased TC,TG, and LDL-C,elevated HDL-C,and lower HOMA-IR;mRNA levels of hepatic PI3K,AKT,and GSK3β and protein expression of p-PI3K, p-AKT, p-GSK3β were significantly upregulated, the differences being statistically significant (P<0.05) . The QDG low-dose and QDG high-dose + PI3K inhibitor groups exhibited attenuated improvements in these parameters versus the QDG high-dose group. Conclusion QDG ameliorates body mass loss,glucose/lipid metabolism,and insulin resistance in T2DM rats,likely by activating the PI3K/AKT/ GSK3β pathway.
[中图分类号]
R285.5
[基金项目]
广东省中医药局科研项目 (编号:20241272) ;深圳市宝安区科技创新局项目 (编号:2024JD308)