首页|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

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

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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。
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
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.

Xiaoke Jianpi Decoction(消渴健脾方)PEDFPI3K/AktAMPKtype 2 diabetesinsulin resistance

郝丛莉、肖艳、王迪、秋金玲

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乌鲁木齐市中医医院,新疆乌鲁木齐 830000

消渴健脾方 PEDF PI3K/Akt AMPK 2型糖尿病 胰岛素抵抗

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
年,卷(期):2025.27(1)