Effect of Zuogui Jiangtang Qinggan Prescription on Glucose and Lipid Metabolism in MKR Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease

WANG Yiyang; ZOU Junju; LU Yuanyuan; XIANG Qin; YU Rong

doi:10.13422/j.cnki.syfjx.20230341

您当前的位置：

首页 >

文章列表页 >

Effect of Zuogui Jiangtang Qinggan Prescription on Glucose and Lipid Metabolism in MKR Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease

更新时间：2023-04-13

- Effect of Zuogui Jiangtang Qinggan Prescription on Glucose and Lipid Metabolism in MKR Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 10, Pages: 102-109(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.20230341
  CLC： R2-0;R22;R33;R289;R587.1
- Published：20 May 2023，
  
  Published Online：23 February 2023，
  
  Received：30 December 2022，
- 稿件说明：
扫描看全文
王一阳,邹俊驹,陆源源等.左归降糖清肝方对2型糖尿病合并非酒精性脂肪性肝病MKR小鼠糖脂代谢的影响[J].中国实验方剂学杂志,2023,29(10):102-109.

WANG Yiyang,ZOU Junju,LU Yuanyuan,et al.Effect of Zuogui Jiangtang Qinggan Prescription on Glucose and Lipid Metabolism in MKR Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(10):102-109.
王一阳,邹俊驹,陆源源等.左归降糖清肝方对2型糖尿病合并非酒精性脂肪性肝病MKR小鼠糖脂代谢的影响[J].中国实验方剂学杂志,2023,29(10):102-109. DOI： 10.13422/j.cnki.syfjx.20230341.

WANG Yiyang,ZOU Junju,LU Yuanyuan,et al.Effect of Zuogui Jiangtang Qinggan Prescription on Glucose and Lipid Metabolism in MKR Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(10):102-109. DOI： 10.13422/j.cnki.syfjx.20230341.

摘要

目的

探讨左归降糖清肝方改善2型糖尿病（T2DM）合并非酒精性脂肪性肝病骨骼肌特异性胰岛素样生长因子-1受体功能缺失（MKR）小鼠糖脂代谢的作用机制。

方法

以MKR小鼠为研究对象，高脂饲料喂养8周诱导形成NAFLD，随机分为模型组、二甲双胍组（0.067 g·kg

-1

）、左归降糖清肝方高、低剂量组（14.8、7.4 g·kg

-1

），同龄FVB小鼠10只作为正常组。分别药物治疗8周后，予以糖耐量测试（OGTT），取血清检测甘油三酯（TG）、总胆固醇（TC），称取小鼠肝脏湿重，取肝组织进行苏木素-伊红（HE）染色、油红O染色观察组织病理形态变化，实时荧光定量聚合酶链式反应（Real-time PCR）及蛋白免疫印迹法（Western blot）检测肝组织叉头框蛋白O1（FoxO1）、磷酸烯醇式丙酮酸羧激酶（PEPCK）、葡萄糖6磷酸酶（G6Pase）、载脂蛋白C3（ApoC-Ⅲ）的mRNA表达及其蛋白表达情况。

结果

与正常组比较，模型组小鼠空腹血糖、肝脏指数、血清TG、血清TC、OGTT水平显著上升（

0.01）；与模型组比较，二甲双胍组及左归降糖清肝方组小鼠空腹血糖、肝脏指数显著下降（

0.01），左归降糖清肝方高剂量组血清的TG、TC水平均明显下降（

0.05，

0.01），二甲双胍组及左归降糖清肝方高剂量组可以降低OGTT水平（

0.05）；在组织病理上，与正常组比较，模型组小鼠可见肝组织脂滴及肝细胞内空泡减少，体积变大；与模型组比较，左归降糖清肝方组和二甲双胍组可见肝组织脂滴减少，肝细胞内空泡减少，体积变小；在分子层面，与正常组比较，模型组小鼠肝组织FoxO1、PEPCK、G6Pase、ApoC-Ⅲ的mRNA水平显著上调（

0.01），FoxO1、PEPCK、G6Pase、ApoC-Ⅲ的蛋白表达显著上调（

0.01）；与模型组比较，左归降糖清肝方组FoxO1、PEPCK、G6Pase、ApoC-Ⅲ的mRNA水平显著下调（

0.01），FoxO1、PEPCK、G6Pase、ApoC-Ⅲ的蛋白表达显著下调（

0.01）。

结论

左归降糖清肝方能改善T2DM合并NAFLD糖脂代谢并能修复肝脏病理损伤，可能是通过调控肝组织FoxO1、PEPCK、G6Pase、ApoC-Ⅲ相关蛋白的表达，达到调脂、降糖及延缓肝脏脂肪病变的作用。

Abstract

Objective

To investigate the mechanism of Zuogui Jiangtang Qinggan prescription （ZJQP） in improving glucose and lipid metabolism in loss of skeletalmuscle-specific insulin-like growth factor-1 receptor function （MKR） mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD）.

Method

NAFLD was induced by high-fat diet feeding for 8 weeks in MKR mice， which were randomly divided into model group， metformin group （0.067 g·kg

-1

）， and ZJQP high and low-dose groups（14.8， 7.4 g·kg

-1

）. Ten FVB mice of the same age were used as the normal group. After 8 weeks of drug treatment， the oral glucose tolerance test （OGTT） was performed， the serum was taken to detect triacylglycerol （TG） and total cholesterol （TC）， and the wet weight of the mouse liver was weighed. Haematoxylin-eosin （HE） staining and oil red O staining were performed to assess histopathology of liver. The mRNA expression and protein expression of Fork head box protein O1 （FoxO1）， phosphoenolpyruvate carboxykinase （PEPCK）， glucose-6-phosphatase （G6Pase）， and apolipoprotein C3 （ApoC-Ⅲ） in liver tissues were detected by real-time fluorescent quantitative PCR （Real-time PCR） and Western blot， respectively.

Result

As compared with the normal group， the levels of fasting blood glucose， liver index， serum TG， TC， and OGTT of mice in the model group increased significantly （

0.01）. As compared with model group， the fasting blood glucose and liver index of the mice in the metformin group and the ZJQP group decreased significantly （

0.01）， the serum levels of TG and TC in the high-dose ZJQP group decreased significantly （

0.05，

0.01）， and the OGTT of mice in the metformin group and the high-dose ZJQP group improved （

0.05）. In histopathology， as compared with the normal group， mice in the model group showed decreased lipid droplets and vacuoles in hepatocytes， and their volumes became larger. Compared with the model group， the ZJQP group and metformin group showed that the lipid droplets in liver tissues were reduced， the vacuoles in liver cells were reduced， and the volume was smaller. At the molecular level， as compared with the normal group， the mRNA and protein levels of FoxO1， PEPCK， G6Pase， and ApoC-Ⅲ in liver tissues of mice in the model group were significantly up-regulated （

0.01）. As compared with the model group， the mRNA and protein levels of FoxO1， PEPCK， G6Pase， and ApoC-Ⅲ in the ZJQP group was significantly decreased （

0.01）.

Conclusion

ZJQP can improve the glucose and lipid metabolism of T2DM with NAFLD and repair the pathological damage of liver， which may be through regulating the expression of FoxO1， PEPCK， G6Pase， ApoC-Ⅲ-related proteins in liver tissues to achieve the effects of regulating lipid， lowering glucose， and delaying hepatic steatosis.

关键词

左归降糖清肝方MKR小鼠2型糖尿病（T2DM）非酒精性脂肪性肝病糖脂代谢

Keywords

Zuogui Jiangtang Qinggan prescriptionMKR micetype 2 diabetes mellitusnon-alcoholic fatty liver diseaseglucose and lipid metabolism

references

LONARDO A，BELLENTANI S，ARGO C K，et al.Epidemiological modifiers of non-alcoholic fatty liver disease： Focus on high-risk groups［J］.Dig Liver Dis，2015，47（12）：997-1006.

TARGHER G，COREY K E，BYRNE C D，et al.The complex link between NAFLD and type 2 diabetes mellitus-mechanisms and treatments［J］.Nat Rev Gastroenterol Hepatol，2021，18（9）：599-612.

程莉娟，成细华，喻嵘，等.滋阴益气活血解毒法治疗32例2型糖尿病合并非酒精性脂肪肝的临床观察［J］.中华中医药杂志，2013，28（9）：2807-2810.

喻嵘，陈大舜，易法银，等.左归降糖方治非胰岛素依赖型糖尿病临床研究［J］.辽宁中医杂志，1999（8）：13-14.

成细华，喻嵘，胡伟，等.左归降糖清肝方含药血清对脂肪酸孵育的HepG2细胞脂肪变性的影响［J］.中国老年学杂志，2015，35（5）：1307-1309.

成细华，程莉娟，绕春梅，等.滋阴益气活血解毒中药含药血清对脂肪变性HepG2细胞SREBP-1c和FAS表达的影响［J］.北京中医药大学学报，2014，37（12）：812-815.

陈聪，陈家旭，喻嵘，等.左归降糖清脂方对2型糖尿病合并非酒精性脂肪性肝病MKR鼠肝组织PI3K信号通路的影响［J］.中华中医药杂志，2021，36（1）：106-111.

程莉娟，成细华，喻嵘，等.左归降糖清肝方对小鼠糖尿病合并脂肪肝脂代谢相关基因mRNA表达的影响［J］.中国老年学杂志，2013，33（17）：4182-4184.

魏冠德.左归降糖清脂方调控PPAR-α、CYP2E1表达改善MKR转基因鼠2型糖尿病合并脂肪肝的作用研究［D］.长沙：湖南中医药大学，2012.

吴勇军，成细华，喻嵘，等.左归降糖清脂方对2型糖尿病转基因MKR鼠脂肪肝发生的影响［J］.中国实验方剂学杂志，2011，17（5）：140-143.

PEREIRA R M，DA CRUZ RODRIGUES K C ，SANT'ANA M R，et al.FOXO1 is downregulated in obese mice subjected to short-term strength training［J］.J Cell Physiol，2022，237（11）：4262-4274.

PEK S，SUM C F，YEOH L Y，et al.Association of apolipoprotein-CⅢ （ApoC-Ⅲ），endothelium-dependent vasodilation and peripheral neuropathy in a multi-ethnic population with type 2 diabetes［J］.Metabolism，2017，72：75-82.

孙文杰，赵能江，李博，等.《中国2型糖尿病防治指南（2020年版）》推荐中成药品种述评［J］.中国中医药信息杂志，2022，29（3）：1-5.

LI Y，TENG D，SHI X，et al.Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association： National cross sectional study［J］.BMJ，2020，369：m997.

ANSTEE Q M，TARGHER G，DAY C P.Progression of NAFLD to diabetes mellitus， cardiovascular disease or cirrhosis［J］.Nat Rev Gastroenterol Hepatol，2013，10（6）：330-344.

BUZZETTI E，PINZANI M，TSOCHATZIS E A.The multiple-hit pathogenesis of non-alcoholic fatty liver disease （NAFLD）［J］.Metabolism，2016，65（8）：1038-1048.

FANG Y L，CHEN H，WANG C L，et al.Pathogenesis of non-alcoholic fatty liver disease in children and adolescence：From "two hit theory" to "multiple hit model"［J］.World J Gastroenterol，2018，24（27）：2974-2983.

PEARSON E R.Type 2 diabetes：A multifaceted disease［J］.Diabetologia，2019，62（7）：1107-1112.

MOLINARO A，BECATTINI B，MAZZOLI A，et al.Insulin-driven PI3K-Akt signaling in the hepatocyte is mediated by redundant PI3Kα and PI3Kβ activities and is promoted by RAS［J］.Cell Metab，2019，29（6）：1400-1409.

刘宏民，吴洁洁，陈欢，等.基于InsR/PI3K/Akt通路研究岩黄连总碱纠正高脂喂养小鼠糖代谢紊乱的作用机制［J］.中草药，2022，53（12）：3687-3693.

WU Y，PAN Q，YAN H，et al.Novel mechanism of foxo1 phosphorylation in glucagon signaling in control of glucose homeostasis［J］.Diabetes，2018，67（11）：2167-2182.

李颖，曹文富，李金蝶.参麦兰苓汤对2型糖尿病合并非酒精性脂肪肝肝脏脂肪含量及肝纤维化的影响［J］.中华中医药学刊，2022，40（6）：144-148.

RAMMS B，PATEL S，NORA C，et al.ApoC-Ⅲ ASO promotes tissue LPL activity in the absence of ApoE-mediated TRL clearance［J］.J Lipid Res，2019，60（8）：1379-1395.

王雅芝，陈慧.血清载脂蛋白CⅢ在2型糖尿病中的作用研究进展［J］.医学综述，2022，28（13）：2673-2678.

YAMAMOTO R，JENSEN M K，ARONER S，et al.HDL containing apolipoprotein C-Ⅲ is associated with insulin sensitivity：A multicenter cohort study［J］.J Clin Endocrinol Metab，2021，106（8）：e2928-e2940.

TANAKA H，NAGASHIMA T，SHIMAYA A，et al.Effects of the novel FoxO1 inhibitor AS1708727 on plasma glucose and triglyceride levels in diabetic db/db mice［J］.Eur J Pharmacol，2010，645（1/3）：185-191.

于淼，朴春丽，南征，等.2型糖尿病胰岛素抵抗的肝内炎症发病机制与毒损肝络病机理论的相关性探讨［J］.中国中西医结合杂志，2006，26（11）：1032-1034.

许凯凯，田露.《黄帝内经》“食气入胃”新解［J］.中医学报，2021，36（11）：2293-2296.

喻嵘，成细华，胡伟，等.骨骼肌特异性胰岛素样生长因子1及胰岛素双受体功能缺失所致小鼠2型糖尿病［J］.中国糖尿病杂志，2008，16（7）：438-440.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mechanism of Zishen Qinggan Prescription in Improving Glucose and Lipid Metabolism in Type 2 Diabetes Based on Transcriptomics

Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy

Mechanism of Astragaloside Ⅳ on db/db Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease Based on AMPK Signaling Pathway

Effect of Modified Cangfu Daotantang on Glucose and Lipid Metabolism in Simple Obese Children with Phlegm Dampness and Stagnation

Related Author

WANG Jingcun

TIAN Chunyu

ZHANG Fan

LA Xiaojin

WU Fanwu

ZHU Liang

MA Leilei

WANG Rui

Related Institution

Tangshan Key Laboratory of Chinese Medicine Pharmacology

North China University of Science and Technology

Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications

Hebei Key Laboratory for Chronic Diseases

School of Pharmacy， North China University of Science and Technology

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