辽宁中医药大学学报2025,Vol.27Issue(1) :22-27.DOI:10.13194/j.issn.1673-842X.2025.01.004

消渴健脾方通过调控PEDF激活PI3K/Akt及AMPK信号通路对2型糖尿病胰岛素抵抗的影响及可能机制

Effect of Xiaoke Jianpi Decoction(消渴健脾方)on Insulin Resistance in Type 2 Diabetes Mellitus by Regulating PEDF and Activating PI3K/Akt and AMPK Signaling Pathways and Its Possible Mechanism

郝丛莉 肖艳 王迪 秋金玲
辽宁中医药大学学报2025,Vol.27Issue(1) :22-27.DOI:10.13194/j.issn.1673-842X.2025.01.004

消渴健脾方通过调控PEDF激活PI3K/Akt及AMPK信号通路对2型糖尿病胰岛素抵抗的影响及可能机制

Effect of Xiaoke Jianpi Decoction(消渴健脾方)on Insulin Resistance in Type 2 Diabetes Mellitus by Regulating PEDF and Activating PI3K/Akt and AMPK Signaling Pathways and Its Possible Mechanism

郝丛莉 1肖艳 1王迪 1秋金玲1
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作者信息

  • 1. 乌鲁木齐市中医医院,新疆乌鲁木齐 830000
  • 折叠

摘要

目的 探讨消渴健脾方通过调控色素上皮衍生因子(pigment epithelium-derived factor,PEDF)激活磷脂酰肌醇-3-激酶/蛋白激酶B(phosphoinositide-3-Kinase/Protein kinase B,PI3K/Akt)及腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)信号通路对2 型糖尿病(Type 2 Diabetes Mellitus,T2DM)胰岛素抵抗(Insulin Resistance,IR)的影响及可能机制.方法 36只实验大鼠按照随机数字法分为7组,对照组、2型糖尿病模型组、盐酸二甲双胍+T2DM大鼠组、消渴健脾方低剂量组、消渴健脾方中剂量组、消渴健脾方高剂量组,每组各6只.对比不同组大鼠体质量、全血血糖、空腹胰岛素(fasting Insulin,FINS)、肝功能、血脂四项、肝糖原的表达变化、p-PI3K、p-Akt、糖原合成酶激酶-3β(glycogen synthase kinase-3β,p-GSK-3β)、p-AMPK、脂肪甘油三酯水解酶(adipose Triglyceride Lipase,ATGL)的蛋白表达水平及β-actin实时荧光定量聚合酶链反应(Real-time Polyme rase Chain Reaction,RT-PCR)引物、观察组织病理变化.结果 药物干预后,盐酸二甲双胍+T2DM大鼠组、消渴健脾方中剂量组及消渴健脾方低剂量组的谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspertate aminotransferase,AST)、总胆固醇(total cholestrol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL)表达量较2型糖尿病模型组显著降低,高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)的表达量显著升高(P<0.05);盐酸二甲双胍+T2DM大鼠组、消渴健脾方中剂量组及消渴健脾方低剂量组的空腹血糖(fasting blood glucose,FBG)、FINS、糖化血红蛋白(glycosylated hemoglobin A1e,HbA1c)及IR值较2型糖尿病模型组显著降低(P<0.05);盐酸二甲双胍+T2DM大鼠组、消渴健脾方中剂量组及消渴健脾方低剂量组的肝糖原及肝脏组织中PEDF含量较2型糖尿病模型组显著升高,血清中的PEDF的含量显著降低(P<0.05);消渴健脾方高剂量组的肝糖原及肝脏组织中PEDF的含量较盐酸二甲双胍+T2DM大鼠组降低,血清中的PEDF的含量升高(P<0.05).苏木精-伊红染色法(hematoxylin-eosin staining,HE)病理结果表明:2型糖尿病模型组肝脏肝细胞排列紊乱、凝固性坏死、水肿、细胞核数量降低.消渴健脾方中剂量组的PI3K、Akt、GSK-3β、AMPK、ATGL的表达水平及β-actin荧光实时定量PCR引物水平较2型糖尿病模型组显著升高(P<0.05).结论 中剂量消渴健脾方存在通过增强T2DM大鼠对PEDF激活的PI3K/Akt及AMPK信号通路水平情况,降低肝糖原及肝脏组织中PEDF的含量增高血清中的PEDF的含量,从而减轻IR程度,推测这是降低血糖的可能机制.

Abstract

Objective To explore the effect and possible mechanism of Xiaoke Jianpi Decoction(消渴健脾方)on insulin resistance(IR)in type 2 diabetes mellitus(T2DM)by regulating pigment epithelium-derived factor(PEDF)to activate phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)and adenosine monophosphate-activated protein kinase(AMPK)signaling pathways.Methods 36 experimental rats were randomly divided into 7 groups'control group,type 2 diabetes model group,metformin hydrochloride+T2DM rat group,low-dose Xiaoke Jianpi Decoction group,middle-dose Xiaoke Jianpi Decoction group and high-dose Xiaoke Jianpi Decoction group,with 6 rats in each group.The expression changes of body weight,whole blood glucose,fasting insulin(FINS),liver function,blood lipid,liver glycogen,protein expression levels of p-PI3K,p-Akt,p-GSK-3β,p-AMPK and adipose triglyceride lipase(ATGL),β-actin fluorescence real-time quantitative PCR primers and histopathological changes were compared in different groups.Results After drug intervention,the expressions of ALT,AST,TC,TG and LDL in metformin hydrochloride+T2DM rat group,middle-dose Xiaoke Jianpi Decoction group and low-dose Xiaoke Jianpi Decoction group were significantly lower than those in type 2 diabetes model group,while the expression of HDL-C was significantly higher(P<0.05).FBG,FINS,HbA1c and IR values in metformin hydrochloride+T2DM rat group,middle-dose Xiaoke Jianpi Decoction group and low-dose Xiaoke Jianpi Decoction group were significantly lower than those in type 2 diabetes model group(P<0.05).Compared with the model group of type 2 diabetes mellitus,the contents of hepatic glycogen and PEDF in the rat group of metformin hydrochloride+T2DM,middle-dose Xiaoke Jianpi Decoction group and low-dose Xiaoke Jianpi Decoction group were significantly higher,and the content of PEDF in serum was significantly lower(P<0.05).Compared with metformin hydrochloride+T2DM rat group,the content of hepatic glycogen and PEDF in the high-dose Xiaoke Jianpi Decoction group decreased,while the content of PEDF in serum increased(P<0.05).HE pathological results of he showed that the arrangement of liver hepatocytes in type 2 diabetes model group was disordered,coagulative necrosis,edema and the number of nuclei decreased.The expression levels of PI3K,Akt,GSK-3β,AMPK,ATGL and the level of β-actin fluorescent real-time quantitative PCR primers in the middle-dose Xiaoke Jianpi Decoction group were significantly higher than those in the model group of type 2 diabetes mellitus(P<0.05).Conclusion Middle-dose Xiaoke Jianpi Decoction can decrease the content of liver glycogen and PEDF in liver tissue and increase the content of PEDF in serum by enhancing PI3K/Akt and AMPK signal pathways activated by PEDF in T2DM rats,thus reducing the degree of IR.It is speculated that this is the possible mechanism of lowering blood sugar.

关键词

消渴健脾方/PEDF/PI3K/Akt/AMPK/2型糖尿病/胰岛素抵抗

Key words

Xiaoke Jianpi Decoction(消渴健脾方)/PEDF/PI3K/Akt/AMPK/type 2 diabetes/insulin resistance

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出版年

2025
辽宁中医药大学学报
辽宁中医药大学

辽宁中医药大学学报

影响因子:0.775
ISSN:1673-842X
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