Effect of Astragaloside Ⅳ in Regulating PI3K/Akt/FoxO1 Pathway and Inhibiting Hepatic Gluconeogenesis in Diabetic Rats

Tian-jiao JI; Zhong-yuan WANG; Yun-feng ZHU; Yan-hua ZHANG; Jie ZHANG; Wei-zu LI; Wei-ping LI

doi:10.13422/j.cnki.syfjx.20192436

您当前的位置：

首页 >

文章列表页 >

Effect of Astragaloside Ⅳ in Regulating PI3K/Akt/FoxO1 Pathway and Inhibiting Hepatic Gluconeogenesis in Diabetic Rats

Pharmacology | 更新时间：2021-02-09

- Effect of Astragaloside Ⅳ in Regulating PI3K/Akt/FoxO1 Pathway and Inhibiting Hepatic Gluconeogenesis in Diabetic Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 1, Pages: 78-86(2020)
- 作者机构：
  
  1.安徽医科大学，合肥　 230032
  2.安庆医药高等专科学校，安徽安庆　 246052
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20192436
  CLC： R2-0; R285; R289
- Received：21 May 2019，
  
  Published Online：03 September 2019，
  
  Published：05 January 2020
- 稿件说明：
移动端阅览
Tian-jiao JI, Zhong-yuan WANG, Yun-feng ZHU, et al. Effect of Astragaloside Ⅳ in Regulating PI3K/Akt/FoxO1 Pathway and Inhibiting Hepatic Gluconeogenesis in Diabetic Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 78-86.
DOI：

Tian-jiao JI, Zhong-yuan WANG, Yun-feng ZHU, et al. Effect of Astragaloside Ⅳ in Regulating PI3K/Akt/FoxO1 Pathway and Inhibiting Hepatic Gluconeogenesis in Diabetic Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 78-86. DOI： 10.13422/j.cnki.syfjx.20192436.

摘要

目的：

探讨黄芪甲苷对2型糖尿病(T2DM)大鼠肝损伤保护潜在机制及肝组织磷酯酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/叉头框转录因子1(FoxO1)，磷酸烯醇式丙酮酸羧基酶(PEPCK)和葡萄糖6-磷酸酶(G6Pase)蛋白表达的影响。

方法：

6周高糖高脂饮食后，链脲佐菌素(STZ)一次性腹腔注射(0.035 g·kg

-1

)建立T2DM大鼠模型，随机分为正常组、模型组、黄芪甲苷低、中、高剂量组及二甲双胍组。黄芪甲苷低、中、高剂量组灌胃黄芪甲苷0.02，0.04，0.08 g·kg

-1

·d

-1

，二甲双胍组灌胃二甲双胍0.2 g·kg

-1

·d

-1

；给药8周后，于末次灌胃24 h禁食不禁水后处死，测血清肝生化指标，肝脏指数等；采用苏木素-伊红(HE)染色观察肝脏组织病理形态学变化；马松(Masson)染色观察纤维化程度；过碘酸希夫(PAS)染色反应观察细胞内糖原等变化；免疫组化及蛋白免疫印迹法(Western blot)检测各组肝中PI3K/Akt/FoxO1信号蛋白及PEPCK，G6Pase蛋白表达水平。

结果：

与正常组比较，模型组肝脏指数显著升高(

0.01)，肝功能指标丙氨酸氨基转移酶(ALT)，天门冬氨酸氨基转移酶(AST)，总胆固醇(TC)，甘油三酯(TG)的含量显著升高(

0.01)，高密度脂蛋白胆固醇(HDL-C)显著降低(

0.01)，大鼠体质量显著减轻(

0.01)，PI3K/Akt/FoxO1信号减弱(

0.01)，PEPCK，G6Pase蛋白表达水平显著增强(

0.01)；与模型组比较，黄芪甲苷中、高剂量组及二甲双胍组肝功能指标ALT，AST，TC，TG的含量明显降低(

0.05，

0.01)，大鼠体质量明显增加(

0.05，

0.01)，肝组织FoxO1，PEPCK及G6Pase蛋白水平明显降低(

0.05，

0.01)，FoxO1的磷酸化水平明显增强(

0.05，

0.01)。

结论：

黄芪甲苷可能通过调节PI3K/Akt/FoxO1信号通路抑制高脂高糖加小剂量STZ诱导T2DM肝糖异生，从而起到延缓T2DM大鼠肝脏损伤作用。

Abstract

Objective:

To investigate the potential mechanism of astragaloside Ⅳ in protecting liver injury and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkheadbox transcription factor 1 (FoxO1)

phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) protein expressions in type 2 diabetic (T2DM) rats.

Method:

After 6 weeks of high-sugar and high-fat diet

a model of type 2 diabetes was established through intraperitoneal injection of streptozotocin (STZ

0.035 g·kg

-1

). The rats were randomly divided into normal group

model group

low

medium and high-dose astragaloside Ⅳ groups and metformin group

0.02

0.04

0.08 g·kg

-1

·d

-1

astragaloside crude drug and 0.2 g·kg

-1

·d

-1

metformin were administered in the low

middle and high-dose astragaloside Ⅳ and metformin groups. After 8 weeks of continuous administration

and 24 hours later after the last gavage

the rats were executed. Serum and liver tissues were collected to detect serum liver biochemical indexes

liver index HDL-C. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue. Masson staining was used to observe the degree of liver fibrosis. The changes of glycogen

glycoprotein

or mucopolysaccharide in tissue cells were observed by periodic acid Schiff (PAS) reaction staining. Immunohistochemistry and Western blot analysis were used to detect the expression levels of PI3K/Akt/FoxO1 signaling protein and PEPCK and G6Pase in liver tissues of each group.

Result:

Compared with normal group

the liver index of the model group increased significantly (

0.01)

the levels of liver function indicators alanine aminotransferase(ALT)

aspartate aminotransferase(AST)

TC and TG were significantly increased (

0.01)

while HDL-C and body weight were significantly reduced (

0.01). The results of immunohistochemistry and Western blot showed that the signal of PI3K/Akt/FoxO1 was weakened (

0.01)

and PEPCK and G6Pase were increased (

0.01) in model group. Compared with model group

the contents of ALT

AST

TC and TG in middle and high-dose astragaloside Ⅳ groups were significantly decreased (

0.05

0.01)

while the body weight was significantly increased (

0.05

0.01)

the middle and high dose of astragaloside Ⅳ significantly inhibited the levels of FoxO1

PEPCK and G6Pase in liver tissue (

0.05

0.01)

and enhanced the phosphorylation of FoxO1 (

0.05

0.01).

Conclusion:

Astragaloside Ⅳ may inhibit T2DM hepatic gluconeogenesis by regulating PI3K/Akt/FoxO1 signaling pathway

and inhibiting high-fat

high-sugar and low-dose STZ

thereby protecting liver damage in T2DM rats.

关键词

Keywords

references

S Sancheti ， S Sancheti ， M Bafna ， et al . Antihyperglycemic，antihyperlipidemic，and antioxidant effects of Chaenomelessinensis fruit extract in streptozotocin-induced diabetic rats [J]． Eur Food Res Technol ， 2010 ， 231 ( 3 )： 415 - 421 .

J M M Evans ， R W Newton ， D A Ruta ， et al . Socio-economic status，obesity and prevalence of Type 1 and Type 2 diabetes mellitus [J]． Diabet Med ， 2000 ， 17 ( 6 )： 478 - 480 .

N Holman ， B Young ， R Gadsby ． Current prevalence of Type 1 and Type 2 diabetes in adults and children in the UK [J]． Diabetic Med ， 2015 ， 32 ( 9 )： 1119 - 1120 .

史文丽，李鹤玲．不同饮食方法治疗2型糖尿病的效果观察 [J]．卫生职业教育， 2011 ， 29 ( 10 )： 139 - 140 .

P J Klover ， R A Mooney ． Hepatocytes: critical for glucose homeostasis [J]． Int J Biochem Cell B ， 2004 ， 36 ( 5 )： 753 - 758 .

T LIU ， C SHI ， R GAO ， et al . Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes [J]． Clin Sci ， 2015 ， 129 ( 10 )： 839 - 850 .

曹玉冰．黄芪甲苷的药理作用及其机制的研究进展 [J]．现代药物与临床， 2017 ， 32 ( 5 )： 954 - 960 .

张蔷，高文远，满淑丽．黄芪中有效成分药理活性的研究进展 [J]．中国中药杂志， 2012 ， 37 ( 21 )： 3203 - 3207 .

L LIN ， S WU ， G WANG ， et al . Effect of astragaloside Ⅳ on hepatic glucose-regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin [J]． Phytother Res ， 2010 ， 24 ( 2 )： 219 - 224 .

B JIANG ， Y YANG ， H JIN ， et al . Astragaloside Ⅳ attenuates lipolysis and improves insulin resistance induced by TNF α in 3T3-L1 adipocytes [J]． Phytother Res ， 2008 ， 22 ( 11 )： 1434 - 1439 .

X MAO ， Y WU ， K WU ， et al . Astragaluspolysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model [J]. Acta Pharmacol Sin ， 2010 ， 28 ( 12 )： 1947 - 1956 .

徐源，黄存东，李竹青，等．黄芪甲苷对糖尿病大鼠肝损伤保护作用及其机制研究 [J]．安徽医科大学学报， 2017 ， 52 ( 12 )： 81 - 87 .

张婷，郭建友．地骨皮煎煮液对多囊卵巢大鼠胰岛素信号传导途径中PI3K/PKB分子表达的影响 [J]．中国中药杂志， 2015 ， 40 ( 10 )： 2004 - 2008 .

邓娟娟，张丹，韩晴，等．活性维生素D对2型糖尿病大鼠肾组织胰岛素信号通路PI3K/Akt的影响 [J]．山西医科大学学报， 2015 ， 46 ( 7 )： 617 - 620 .

许金榜，王小云，纪峰，等．痰脂消汤调控PCOS-IR模型大鼠卵巢PI3K/Akt途径探讨 [J]．中国实验方剂学杂志， 2016 ， 22 ( 24 )： 156 - 160 .

冯琳晶，于洋，杜红伟． FoxO1在胰岛 β 细胞代谢灵活性受损及失代偿进程中的作用 [J]．中国生物工程杂志， 2018 ， 38 ( 6 )： 70 - 76 .

黄宁，李文佳，安利国，等． FoxO1的功能及其与人类疾病的关系 [J]．生命科学， 2012 ， 24 ( 4 )： 334 - 339 .

马可可，鞠营辉，陈清青，等．黄芪甲苷对2型糖尿病肾病大鼠肾组织PI3K/Akt/FoxO1信号调控的影响 [J]．中国实验方剂学杂志， 2019 ， 25 ( 2 )： 74 - 81 .

黄文凡，文秀英，余杰． FoxO1转录因子在肝脏糖脂代谢中的作用 [J]．中西医结合研究， 2010 ， 2 ( 6 )： 317 - 320 .

赵航，张运佳，树林一，等． FoxO1在肝脏糖脂代谢中的作用 [J]．基础医学与临床， 2019 ， 39 ( 1 )： 115 - 119 .

徐淑云．药理实验方法学 [M]．北京：人民卫生出版社， 2002 ： 192 - 193 .

林心君．基于PI3K/Akt和GCGR/PKA通路探讨石斛合剂抑制糖异生的机制 [D]．福州：福建中医药大学， 2018 ： 45 - 49 .

唐海波． PI3K/Akt/FoxO3a在非酒精性脂肪肝发病机制中的作用 [D]．长沙：中南大学， 2013 .

刘培，王鹏飞，王科，等．基于PI3K/Akt通路的中药治疗糖尿病研究进展 [J]．中国实验方剂学杂志， 2019 ， 25 ( 5 )： 220 - 228 .

王帅，金磊，海春旭，等． PI3K/Akt信号通路在胰岛素抵抗中作用的研究进展 [J]．毒理学杂志， 2015 ， 29 ( 4 )： 313 - 316 .

迟毓婧，李晶，管又飞，等． PI3K-Akt信号传导通路对糖代谢的调控作用 [J]．中国生物化学与分子生物学报， 2010 ， 26 ( 10 )： 879 - 885 .

陈洁，刘一然．姜黄素对2型糖尿病大鼠脂肪细胞葡萄糖转运及PI3K/Akt信号通路的影响 [J]．中国比较医学杂志， 2019 ， 29 ( 5 )： 90 - 97 .

龚又明，郑显辉，谢鸣坤，等．小檗碱对HepG2胰岛素抵抗细胞PI3K/AKT1/GLUT1信号通路的调控作用 [J]．新中医， 2017 ， 49 ( 8 )： 12 - 15 .

L ZHANG ， Z GUO ， Y WANG ， et al . The protective effect of kaempferol on heart via the regulation of Nrf2，NF- κ B，and PI3K/Akt/GSK-3 β signaling pathways in isoproterenol-induced heart failure in diabetic rats [J]． Drug Develop Res ， 2019 ， 80 ( 3 )： 294 - 309 .

金其贯，张奥英，刘瑜，等．有氧运动和补充魔芋葡甘聚糖通过调节PI3K/FoxO1通路有效预防高脂膳食大鼠肝脏胰岛素抵抗的形成 [J]．中国运动医学杂志， 2018 ， 37 ( 8 )： 685 - 691 .

J Nakae ， W H Biggs ， T Kitamura ， et al . Regulation of insulin action and pancreatic β -cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1 [J]． Nat Genet ， 2002 ， 32 ( 2 )： 245 - 253 .

Z CHENG ， M F White ． Targeting forkhead box O1 from the concept to metabolic diseases：lessons from mouse models [J]． Antioxid Redox Sign ， 2011 ， 14 ( 4 )： 649 - 661 .

Q WANG ， N WANG ， M DONG ， et al . GdCl3 reduces hyperglycaemia through Akt/FoxO1-induced suppression of hepatic gluconeogenesis in Type2 diabetic mice [J]． Clin Sci ， 2014 ， 127 ( 2 )： 91 - 100 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of Gynostemma pentaphyllum Alcohol Extract on Glucose and Lipid Metabolism Disorders in db/db Mice Based on Transcriptomics and Gut Microbiota

Analysis of Mechanism of Astragaloside Ⅳ in Regulating Ferroptosis Through SLC7A11/GPX4 Pathway Against Vascular Smooth Muscle Cell Proliferation

Mechanism of Astragaloside Ⅳ in Regulating PI3K/Akt Molecular Pathway in Prevention and Treatment of Diabetes Complications： A Review

Mechanism of Action of Coptidis Rhizoma and Ophiopogonis Radix in Delaying Diabetic Nephropathy Based on EGFR/PI3K/Akt Signaling Pathway

Effect and Mechanism of Zuogui Jiangtang Yishen Prescription on Diabetic Kidney Disease in Rats via Regulation of MiRNA-27a/Wnt/β-catenin Pathway

Related Author

ZHU Yifei

DING Lei

LIU Wei

SUN Yahui

QIN Lingling

WU Lili

LIU Tonghua

LI Guoting

Related Institution

Dongfang Hospital， Beijing University of Chinese Medicine

Beijing University of Chinese Medicine

Key Laboratory of Traditional Chinese Medicine Health Care，Beijing University of Chinese Medicine

Hebei Key Laboratory of Traditional Chinese Medicine（TCM） Research on Cardiocerebrovascular Disease，TCM Processing Technology Innovation Center of Hebei Province，College of Pharmacy， Hebei University of Chinese Medicine

Anhui University of Chinese Medicine

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰