Effect of Baihu Jia Renshen Tang on PI3K/Akt Signaling Pathway in Liver of MKR Diabetic Mice

CHEN Yutong; YU Rong; WU Yuqin; XIANG Qin; TAN Yan; ZHOU Cong

doi:10.13422/j.cnki.syfjx.20230594

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Effect of Baihu Jia Renshen Tang on PI3K/Akt Signaling Pathway in Liver of MKR Diabetic Mice

更新时间：2023-02-07

- Effect of Baihu Jia Renshen Tang on PI3K/Akt Signaling Pathway in Liver of MKR Diabetic Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 5, Pages: 114-121(2023)
- 作者机构：
  
  湖南中医药大学，长沙 410208
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230594
  CLC： R22;R242;R2-031;R285.5;R587.1;R255.4
- Published：05 March 2023，
  
  Published Online：16 August 2022，
  
  Received：27 April 2022，
- 稿件说明：
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陈昱彤,喻嵘,吴玉芩等.白虎加人参汤对MKR糖尿病鼠肝脏PI3K/Akt信号通路的影响[J].中国实验方剂学杂志,2023,29(05):114-121.

CHEN Yutong,YU Rong,WU Yuqin,et al.Effect of Baihu Jia Renshen Tang on PI3K/Akt Signaling Pathway in Liver of MKR Diabetic Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(05):114-121.
陈昱彤,喻嵘,吴玉芩等.白虎加人参汤对MKR糖尿病鼠肝脏PI3K/Akt信号通路的影响[J].中国实验方剂学杂志,2023,29(05):114-121. DOI： 10.13422/j.cnki.syfjx.20230594.

CHEN Yutong,YU Rong,WU Yuqin,et al.Effect of Baihu Jia Renshen Tang on PI3K/Akt Signaling Pathway in Liver of MKR Diabetic Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(05):114-121. DOI： 10.13422/j.cnki.syfjx.20230594.

摘要

目的

探究白虎加人参汤对MKR糖尿病模型小鼠肝脏磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路相关分子的作用。

方法

选取30只6周龄MKR小鼠，经高脂饲料喂养4周后予以腹腔注射链脲佐菌素（STZ）进行糖尿病造模，检测空腹血糖值≥11.1 mmol·L

-1

即造模成功，造模成功后随机分成模型组、白虎加人参汤组、二甲双胍组，每组各10只，同时设10只FVB鼠为空白组，各药物干预组分别持续给药28 d，药物剂量分别为白虎加人参汤组12.09 g·kg

-1

·d

-1

、二甲双胍组0.065 g·kg

-1

·d

-1

。给药结束后处死小鼠检测口服葡萄糖耐量实验（OGTT）及空腹血糖（FBG），半定量酶联免疫吸附测定法（ELISA）测定血清极低密度脂蛋白（VLDL）含量，血生化仪测定血脂4项；肝脏组织进行苏木素-伊红（HE）病理学检测；蛋白免疫印迹法（Western blot）检测小鼠肝脏组织PI3K、Akt、磷酸化PI3K（p-PI3K）、磷酸化Akt（p-Akt）、叉头框蛋白O1（FoxO1）、胰岛素受体（InsR）、胰岛素受体底物-2（IRS-2）蛋白表达；实时荧光定量聚合酶链式反应（Real-time PCR）检测小鼠肝脏组织PI3K、Akt、FoxO1、InsR、IRS-2 mRNA表达。

结果

与空白组比较，模型组小鼠一般情况较差，糖耐量异常（

0.05），空腹血糖显著升高（

0.01），血脂代谢异常，血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、VLDL水平明显升高（

0.05），高密度脂蛋白胆固醇（HDL-C）水平明显降低（

0.05），肝脏细胞脂肪样变性，发生明显病理改变，肝脏组织PI3K、Akt、p-PI3K/PI3K、p-Akt/Akt、IRS-2、InsR蛋白含量明显降低（

0.05）；FoxO1蛋白含量明显增加（

0.05），肝脏组织PI3K、Akt、IRS-2、InsR mRNA表达量减少（

0.05），FoxO1 mRNA表达量增加（

0.05）。与模型组比较，白虎加人参汤组小鼠一般情况出现好转，糖脂代谢得到改善（

0.05），肝脏细胞病理状态好转，肝脏组织PI3K、Akt、p-PI3K/PI3K、p-Akt/Akt、IRS-2、InsR蛋白含量明显升高（

0.05）；FoxO1蛋白含量明显降低

（P

0.05），肝脏组织PI3K、Akt、IRS-2、InsR mRNA表达量增加

（P

0.05），FoxO1 mRNA表达量减少（

0.05）。

结论

白虎加人参汤能有效降低MKR糖尿病小鼠血糖、调节血脂代谢并改善其肝脏的病理状态，其作用机制可能是通过调控PI3K/Akt通路上信号分子的活性有关。

Abstract

Objective

To explore the effects of Baihu Jia Renshen Tang （BHRS） on the related molecules on the phosphatidylinositol-3-kinase/protein kinase B（PI3K/Akt）signaling pathway in the liver of MKR diabetic model mice.

Method

Thirty 6-week-old MKR mice were selected and fed on a high-fat diet for four weeks，followed by intraperitoneal injection of streptozotocin（STZ）for the diabetes model establishment. The model was properly induced in the case of the fasting blood glucose （FBG） of ≥11.1 mmol·L

-1

. After modeling，the mice were randomly divided into a model group，a BHRS group （12.09 g·kg

-1

·d

-1

），and a metformin group （0.065 g·kg

-1

·d

-1

），with 10 mice in each group. Ten FVB mice were assigned to the control group. The mice in the groups with drug intervention were continuously administered correspondingly for 28 days. After administration，the mice were sacrificed，followed by the oral glucose tolerance test （OGTT） and FBG detection. Serum very low-density lipoprotein（VLDL）content was determined by semi-quantitative enzyme-linked immunosorbent assay （ELISA）. Four indexes related to blood lipid were determined by the biochemistry analyzer. Liver tissues were subjected to pathological examination by hematoxylin-eosin（HE）staining. Western blot was used to detect the protein expression of PI3K，Akt，phosphorylated（p）-PI3K，p-Akt，forkhead box protein O1 （FoxO1），insulin receptor（InsR），and insulin receptor substrate-2（IRS-2） in liver tissues of mice. Real-time polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression of PI3K，Akt，FoxO1，InsR，and IRS-2 in liver tissues of mice.

Result

Compared with the control group，the model group showed poor general conditions，abnormal glucose tolerance （

0.05），increased FBG （

0.01），abnormal blood lipid metabolism，increased serum total cholesterol （TC），triglyceride（TG），low-density lipoprotein cholesterol（LDL-C），and VLDL （

0.05），decreased level of high-density lipoprotein cholesterol（HDL-C）（

0.05），fatty degeneration and obvious pathological changes of liver cells，reduced protein expression of PI3K，Akt，p-PI3K/PI3K，p-Akt/Akt，IRS-2，and InsR in liver tissues（

0.05），increased protein expression of FoxO1（

0.05），decreased mRNA expression of PI3K，Akt，IRS-2，and InsR in liver tissues （

0.05），and increased FoxO1 mRNA expression（

0.05）. Compared with the model group，the BHRS group showed improved general conditions and glucose and lipid metabolism （

0.05），improved pathological state of liver cells，increased protein expression of PI3K，Akt，p-PI3K/PI3K，p-Akt/Akt，IRS-2，and InsR in liver tissues（

0.05），decreased protein expression of FoxO1（

0.05），increased mRNA expression of PI3K，Akt，IRS-2，and InsR in liver tissues （

0.05），and reduced FoxO1 mRNA expression（

0.05）.

Conclusion

BHRS can effectively reduce blood glucose，regulate blood lipid metabolism，and improve the pathological state of the liver in MKR diabetic mice，and its mechanism of action may be related to the regulation of the activity of molecules on the PI3K/Akt signaling pathway.

关键词

白虎加人参汤磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路2型糖尿病糖脂代谢

Keywords

Baihu Jia Renshen Tangphosphatidylinositol-3-kinase/protein kinase B（PI3K/Akt）signaling pathwaytype 2 diabetesglucose and lipid metabolism

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