[1]张萌,黄倩,周长静,等.基于PI3K/AKT/GLUT4通路探讨乌葛丹丸改善2型糖尿病胰岛素抵抗作用机制[J].陕西中医,2025,46(6):734-740.[doi:DOI:10.3969/j.issn.1000-7369.2025.06.003]
　ZHANG Meng,HUANG Qian,ZHOU Changjing,et al.Effect and mechanism of Wugedan pill on insulin resistance in type 2 diabetes mellitus based on PI3K/AKT/GLUT4 pathway[J].,2025,46(6):734-740.[doi:DOI:10.3969/j.issn.1000-7369.2025.06.003]
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基于PI3K/AKT/GLUT4通路探讨乌葛丹丸改善2型糖尿病胰岛素抵抗作用机制
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
46
期数:
2025年6期
页码:
734-740
栏目:
基础研究
出版日期:
2025-06-05

文章信息/Info

Title:
Effect and mechanism of Wugedan pill on insulin resistance in type 2 diabetes mellitus based on PI3K/AKT/GLUT4 pathway
作者:
张萌1; 黄倩2; 周长静3; 乔园4; 王高雷2; 肖洋2; 刘德亮5; 成路平3
（1.西安国际医学中心医院，陕西 西安 710100；2.陕西省中医医院，陕西 西安 710003； 3.安康市中医医院，陕西 安康 725000；4.陕西省中医药研究院，陕西 西安 710003；5.深圳市中医院，广东 深圳 518033）
Author(s):
ZHANG Meng1; HUANG Qian2; ZHOU Changjing3; QIAO Yuan4; WANG Gaolei2; XIAO Yang2; LIU Deliang5; CHENG Luping2
(1.Xi’an International Medical Center Hospital,Xi’an 710100,China;2.Shaanxi Provincial Hospital of Traditional Chinese Medicine,Xi’an 710003,China;3.Ankang Hospital of Traditional Chinese Medicine,Ankang 725000,China;4.Shaanxi Academy of Traditional Chinese Medicine,Xi’an 710003,China;5.Shenzhen Traditional Chinese Medicine Hospital，Shenzhen 518033，China)
关键词:
2型糖尿病; 乌葛丹丸; 消渴病; 信号通路; 胰岛素抵抗; 磷脂酰肌醇-3-羟激酶
Keywords:
Type 2 diabetes mellitus; Wugedan pill; Diabetes; Signaling pathway; Insulin resistance; Phosphatidylinositol 3-kinase
分类号:
R 587.1
DOI:
DOI:10.3969/j.issn.1000-7369.2025.06.003
文献标志码:
A
摘要:
目的：观察乌葛丹丸对2型糖尿病（T2DM）模型大鼠胰岛素抵抗（IR）的影响及其分子机制研究，为乌葛丹丸治疗T2DM提供理论与实验支持。方法：将SD大鼠随机分为空白对照组、模型组、乌葛丹丸高、低剂量组[2.85、0.95 g/（kg·d）]、盐酸二甲双胍组[0.16 g/（kg·d）]，空白对照组给予普通饲料喂养，其余各组予高糖高脂饮食喂养+链脲佐菌素（STZ）腹腔注射构建T2DM模型；各治疗组分别给予相应药物进行干预后，每周称量大鼠体重，测定空腹血糖（FPG）；酶联免疫吸附测定（ELISA）法检测各组大鼠血清中三酰甘油（TG）、总胆固醇（CHO）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平；苏木素-伊红（HE）染色法观察各组大鼠肝脏、胰腺组织病理变化；通过葡萄糖耐量试验测定各组大鼠血糖水平；逆转录荧光定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法(Western blot)检测大鼠肝脏组织中磷脂酰肌醇-3-激酶/蛋白激酶B/葡萄糖转运蛋白4（PI3K/AKT/GLUT4）通路相关基因和蛋白的表达。结果：与模型组相比，乌葛丹丸各剂量组大鼠体重均有降低，但差异无统计学意义；乌葛丹丸不同给药组FPG水平均明显降低，且乌葛丹丸高剂量组显著低于乌葛丹丸低剂量组（均P＜0.05）；葡萄糖耐量试验中各时间段血糖水平均降低，乌葛丹丸高、低剂量组曲线下面积（AUC）显著降低（均P＜0.05），其中乌葛丹丸高剂量组与乌葛丹丸低剂量组相比明显降低（P＜0.05）；乌葛丹丸高、低剂量组大鼠血清TG、CHO、LDL-C水平显著降低，乌葛丹丸高剂量组明显低于乌葛丹丸低剂量组（均P＜0.05），乌葛丹丸高剂量组HDL-C含量显著升高（均P＜0.01）。乌葛丹丸高剂量组肝脏组织中PI3K、AKT、GLUT4的mRNA表达显著增加（均P＜0.05），而乌葛丹丸低剂量组以上各因子mRNA的表达均有提高，但差异无统计学意义；乌葛丹丸高剂量组肝脏中PI3K、AKT及GLUT4蛋白的相对表达量明显增加（均P<0.05），乌葛丹丸低剂量组可促进AKT、GLUT4的表达（均P<0.05）。乌葛丹丸各剂量组大鼠胰岛细胞变性、坏死减轻，肝脏细胞脂质沉积、炎性细胞浸润减少。结论：乌葛丹丸可改善T2DM糖脂代谢紊乱，通过介导PI3K/AKT/GLUT4胰岛素信号传导途径，从而增强细胞转运葡萄糖的能力，改善胰岛素抵抗。
Abstract:
Objective:To observe the therapeutic effect of Wugedan pill on insulin resistance of Type 2 diabetes rat model,and reveal some the mechanisms,providing theoretical and experimental support for the treatment of type 2 diabetes mellitus with Wugedan pill.Methods:SD rats were randomly divided into blank control group,model group,Wugedan pill high-dose group [2.85 g/（kg·d）],Wugedan pill low-dose group [0.95 g/（kg·d）] and metformin hydrochloride group [0.16 g/（kg·d）].The blank control group was fed standard diet.The other groups were given high-carbohydrate and high-fat diet plus STZ solution to establish T2DM model.Results:Compared with the model group,the body weight of the Wugedan rats decreased,but the difference was not statistically significant.FPG level was significantly decreased in different Wugedan pill groups,and the high dose Wugedan pill group was significantly lower than the low dose Wugedan pill group (all P<0.05).The AUC in the high-dose group and the low-dose group was significantly lower than that in the low-dose group (all P<0.05),and the high-dose group was significantly lower than that in the low-dose group (P<0.05).The serum levels of TG,CHO and LDL-C were significantly decreased,and the high dose group was significantly lower than the low dose group (all P<0.05),and the high dose group was significantly higher than the high dose group (P<0.01).The mRNA expression of PI3K,AKT and GLUT4 in the liver tissue of the high-dose group was significantly increased (all P<0.05),while the mRNA expression of the above factors in the low-dose group was increased,but the difference was not statistically significant.The relative expression levels of PI3K,AKT and GLUT4 proteins in the liver of the high-dose group were significantly increased (all P<0.05).The low dose group could promote the expression of AKT and GLUT4 (all P<0.05).The degeneration and necrosis of islet cells,lipid deposition and inflammatory cell infiltration in liver cells were reduced in the Urgedan treatment group.Conclusion:Wugedan pills can improve glucose and lipid metabolism disorders in T2DM by mediating the PI3K/AKT/GLUT4 insulin signal transduction pathway,thereby enhancing the ability of cell to transport glucose,and finally improving insulin resistance.

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备注/Memo

备注/Memo:
国家自然科学基金资助面上项目（82274419）；陕西省重点研发计划项目（2024SF-YBXM-522）；陕西省高水平中医药重点学科建设项目（SXZYYZDXK-2024006）；西安市科学技术局项目（21YXYJ0096）；重庆市教育委员会科学技术研究项目（KJQN202102713）
更新日期/Last Update: 2025-06-09