Effect of Zuogui Jiangtang Tongmai Prescription on SCFAs/GPR43/GLP-1/GLP-1R Signaling Pathway in Rats with Diabetes Mellitus Complicated with Cerebral Infarction

LIU Xun; LIU Hua; PENG Lanyu; LUO Zheng; DENG Yihui

doi:10.13422/j.cnki.syfjx.20231237

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Effect of Zuogui Jiangtang Tongmai Prescription on SCFAs/GPR43/GLP-1/GLP-1R Signaling Pathway in Rats with Diabetes Mellitus Complicated with Cerebral Infarction

更新时间：2023-10-13

- Effect of Zuogui Jiangtang Tongmai Prescription on SCFAs/GPR43/GLP-1/GLP-1R Signaling Pathway in Rats with Diabetes Mellitus Complicated with Cerebral Infarction
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 21, Pages: 86-93(2023)
- 作者机构：
  
  1.湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室，长沙 410208
  2.中国人民解放军南部战区总医院，广州 510010
  3.湖南中医药大学中医学院，长沙 410208
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20231237
  CLC： R2-0;R33;R587.1;R743
- Published：05 November 2023，
  
  Published Online：07 September 2023，
  
  Received：10 April 2023，
- 稿件说明：
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刘迅,刘华,彭岚玉等.左归降糖通脉方对糖尿病合并脑梗死大鼠SCFAs/GPR43/GLP-1/GLP-1R信号通路的影响[J].中国实验方剂学杂志,2023,29(21):86-93.

LIU Xun,LIU Hua,PENG Lanyu,et al.Effect of Zuogui Jiangtang Tongmai Prescription on SCFAs/GPR43/GLP-1/GLP-1R Signaling Pathway in Rats with Diabetes Mellitus Complicated with Cerebral Infarction[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(21):86-93.
刘迅,刘华,彭岚玉等.左归降糖通脉方对糖尿病合并脑梗死大鼠SCFAs/GPR43/GLP-1/GLP-1R信号通路的影响[J].中国实验方剂学杂志,2023,29(21):86-93. DOI： 10.13422/j.cnki.syfjx.20231237.

LIU Xun,LIU Hua,PENG Lanyu,et al.Effect of Zuogui Jiangtang Tongmai Prescription on SCFAs/GPR43/GLP-1/GLP-1R Signaling Pathway in Rats with Diabetes Mellitus Complicated with Cerebral Infarction[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(21):86-93. DOI： 10.13422/j.cnki.syfjx.20231237.

摘要

目的

基于短链脂肪酸（SCFAs）/G蛋白偶联受体43（GPR43）/胰高糖素样肽-1（GLP-1）/胰高糖素样肽-1受体（GLP-1R）信号通路探讨左归降糖通脉方对糖尿病合并脑梗死（DM-CI）大鼠的潜在作用机制。

方法

将60只SD大鼠随机分为假手术组、模型组、左归降糖通脉方低、高剂量组（12、24 g·kg

-1

）和西药组（吡格列酮二甲双胍片140 mg·kg

-1

+阿司匹林肠溶片27 mg·kg

-1

），除假手术组外，其余各组以高糖高脂饮食喂养4周后联合35 mg·kg

-1

1%链脲佐菌素腹腔注射合并大脑中动脉闭塞建立DM-CI大鼠模型。分别用蒸馏水、左归降糖通脉方低、高剂量、吡格列酮二甲双胍片和阿司匹林肠溶片进行相应干预，术后进行神经功能缺损（NIHSS）评分，TTC染色测量大鼠脑梗死体积，测量各组大鼠随机血糖浓度，苏木素-伊红（HE）染色观察大鼠脑组织病理学变化，气相色谱法检测盲肠内容物SCFAs含量，酶联免疫吸附测定法（ELISA）检测血清GLP-1含量，蛋白免疫印迹法（Western blot）检测大鼠回肠组织中GPR43和缺血侧脑组织中GLP-1R的蛋白表达。

结果

与假手术组比较，模型组大鼠NIHSS评分、随机血糖、脑梗死体积显著升高（

0.01），SCFAs、GLP-1含量和GPR43、GLP-1R蛋白表达显著降低（

0.01）；与模型组比较，左归降糖通脉方高剂量组和西药组大鼠NIHSS评分、随机血糖、脑梗死体积明显降低（

0.05，

0.01），SCFAs、GLP-1含量和GPR43、GLP-1R蛋白表达水平显著升高（

0.01）。

结论

左归降糖通脉方可改善DM-CI大鼠糖代谢紊乱、减轻神经功能损伤，其机制可能与左归降糖通脉方增加SCFAs含量，上调GPR43/GLP-1/GLP-1R信号通路的表达有关。

Abstract

Objective

To explore the potential mechanism of Zuogui Jiangtang Tongmai prescription （ZJT） in the treatment of diabetes mellitus complicated with cerebral infarction （DM-CI） in rats based on the short-chain fatty acids （SCFAs）/G protein-coupled receptor 43 （GPR43）/glucagon-like peptide-1 （GLP-1）/GLP-1 receptor （GLP-1R） signaling pathway.

Method

Sixty SD rats were randomly divided into sham operation group， model group， low- and high-dose ZJT groups （12， 24 g·kg

-1

）， western medicine group （140 mg·kg

-1

pioglitazone metformin tablets + 27 mg·kg

-1

enteric-coated aspirin tablets）. Except for the sham operation group， all other groups were fed a high-sugar high-fat diet for 4 weeks and then subjected to intraperitoneal injection of 1% streptozotocin at 35 mg·kg

-1

combined with middle cerebral artery occlusion （MCAO） to establish a DM-CI rat model. The corresponding interventions were performed with distilled water， low-dose ZJT， high-dose ZJT， pioglitazone metformin tablets， and enteric-coated aspirin tablets. After surgery， National Institutes of Health Stroke Scale （NIHSS） scoring and triphenyltetrazolium chloride （TTC） staining to measure the rat's cerebral infarct volume were carried out. Random blood glucose levels were measured， and hematoxylin-eosin （HE） staining was used to observe histopathological changes in rat brain tissues. Gas chromatography was employed to detect the content of SCFAs in the cecum contents. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure serum GLP-1 level. Western blot was used to detect the protein expression of GPR43 in rat ileal tissues and GLP-1R in the ischemic brain tissues.

Result

Compared with the sham operation group， the model group showed significantly increased NIHSS scores， random blood glucose levels， and cerebral infarct volumes （

0.01）， and significantly decreased SCFAs content， GLP-1 levels， and GPR43 and GLP-1R protein expression （

0.01）. Compared with the model group， the high-dose ZJT group and the western medicine group exhibited significantly reduced NIHSS scores， random blood glucose levels， and cerebral infarct volumes （

0.05，

0.01）， and significantly increased SCFAs content， GLP-1 levels， and GPR43 and GLP-1R protein expression （

0.01）.

Conclusion

ZJT can improve glucose metabolism disorder and reduce neurological damage in DM-CI rats， and its mechanism may be related to the increase in SCFAs content and the upregulation of the GPR43/GLP-1/GLP-1R signaling pathway.

关键词

左归降糖通脉方糖尿病合并脑梗死短链脂肪酸短链脂肪酸（SCFAs）/G蛋白偶联受体43（GPR43）/胰高糖素样肽-1（GLP-1）/胰高糖素样肽-1受体（GLP-1R）通路

Keywords

Zuogui Jiangtang Tongmai prescriptiondiabetes mellitus complicated with cerebral infarctionshort-chain fatty acidsshort-chain fatty acids （SCFAs）/G protein-coupled receptor 43 （GPR43）/glucagon like peptide-1 （GLP-1）/GLP-1 receptor （GLP-1R） pathway

references

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.

LI L，LI C.Microvascular complications of diabetes worsen long-term functional outcomes after acute ischemic stroke［J］.J Int Med Res，2018，46（8）：3030-3041.

MA S， WANG J， WANG Y， et al. Diabetes mellitus impairs white matter repair and long-term functional deficits after cerebral ischemia ［J］. Stroke， 2018， 49（10）： 2453-2463.

BéMEUR C，STE-MARIE L，MONTGOMERY J.Increased oxidative stress during hyperglycemic cerebral ischemia［J］.Neurochem Int，2007，50（7/8）：890-904.

张笑栩，杨志强，丁秀芳.从肝肾同治论治糖尿病合并脑梗死的临证经验［J］.实用中医内科杂志，2022，36（9）：142-143.

朱大龙.中国2型糖尿病防治指南（2020年版）（上）［J］.中国实用内科杂志， 2021， 41（8）： 668-695.

邓奕辉，崔莲珠，喻嵘，等.降糖通脉方治疗糖尿病合并脑梗死32例临床观察［J］.湖南中医学院学报，2004，24（5）：40-42.

邓奕辉，李定祥，陈大舜.降糖通脉方对糖尿病合并缺血性脑损伤模型大鼠的影响［J］.湖南中医学院学报，2002，22（1）：10-13.

HU W，KONG X，WANG H，et al.Ischemic stroke and intestinal flora：An insight into brain-gut axis［J］.Eur J Med Res，2022，27（1）：73.

TOLHURST G，HEFFRON H，LAM Y S，et al.Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2［J］.Diabetes，2012，61（2）：364-371.

SHAN Y，TAN S，LIN Y，et al.The glucagon-like peptide-1 receptor agonist reduces inflammation and blood-brain barrier breakdown in an astrocyte-dependent manner in experimental stroke［J］.J Neuroinflammation，2019，16（1）：242.

KRISTENSEN S L，RØRTH R，JHUND P S，et al.Cardiovascular， mortality， and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes：A systematic review and Meta-analysis of cardiovascular outcome trials［J］.Lancet Diabetes Endocrinol，2019，7（10）：776-785.

白波. 新型GLP-1/GIP双受体激动剂对糖尿病脑缺血再灌注模型大鼠内质网应激的影响及其与利拉鲁肽的比较［D］.太原：山西医科大学， 2020.

邵俊伟，蔡逊，马丹丹，等.SD大鼠2型糖尿病模型的建立与评价［J］.中国普外基础与临床杂志，2014，21（10）：1212-1215.

LONGA E Z，WEINSTEIN P R，CARLSON S，et al.Reversible middle cerebral artery occlusion without craniectomy in rats［J］.Stroke，1989，20（1）：84-91.

贺石林，王键，王净净. 中医科研设计与统计学［M］. 长沙：湖南科学技术出版社， 2001.

邓冬，周爽，叶苗青，等.中药复方治疗糖尿病合并脑梗死机制的研究进展［J］.中国实验方剂学杂志，2019，25（13）：214-223.

邓奕辉. 滋阴益气活血法抗糖尿病合并脑梗塞的临床与实验研究［D］.长沙：湖南中医学院， 2001.

李钰佳，李定祥，彭殉，等.基于AMPK/mTOR/ULK1自噬相关通路探讨左归降糖通脉方对AGEs合并缺糖缺氧星形胶质细胞炎性损伤的影响［J］.中国实验方剂学杂志，2022，28（16）：90-99.

XU J，BJURSELL M K，HIMROD J，et al.A genomic view of the human-Bacteroides thetaiotaomicron symbiosis［J］.Science，2003，299（5615）：2074-2076.

KIMURA I， ICHIMURA A， OHUE-KITANO R， et al. Free fatty acid receptors in health and disease ［J］. Physiol Rev， 2020， 100（1）： 171-210.

KIMURA I，OZAWA K，INOUE D，et al.The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43［J］.Nat Commun，2013，4：1829.

COSKUN Z M，KOYUTURK M，KARABULUT S，et al.CB-1R and GLP-1R gene expressions and oxidative stress in the liver of diabetic rats treated with sitagliptin［J］.Pharmacol Rep，2017，69（4）：822-829.

WANG X，ZHOU J，DOYLE M E，et al.Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein translocation from the cytoplasm to the nucleus of pancreatic beta-cells by a cyclic adenosine monophosphate/protein kinase A-dependent mechanism［J］.Endocrinology，2001，142（5）：1820-1827.

KAPODISTRIA K，TSILIBARY E P，KOTSOPOULOU E，et al.Liraglutide， a human glucagon-like peptide-1 analogue， stimulates Akt-dependent survival signalling and inhibits pancreatic β-cell apoptosis［J］.J Cell Mol Med，2018，22（6）：2970-2980.

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

KIMURA R，OKOUCHI M，FUJIOKA H，et al.Glucagon-like peptide-1 （GLP-1） protects against methylglyoxal-induced PC12 cell apoptosis through the PI3K/Akt/mTOR/GCLc/redox signaling pathway［J］.Neuroscience，2009，162（4）：1212-1219.

张超，加秀凤，黄万凌，等.基于PI3K/Akt通路探讨首乌丸对D-半乳糖衰老大鼠海马神经元凋亡的影响［J］.中国实验方剂学杂志，2022，28（22）：76-84.

宋军营，丁蕊，李俊霖，等.六味地黄丸通过PI3K/Akt/FoxO3a通路调控自噬对SAMP8小鼠记忆功能的影响［J］.中国实验方剂学杂志，2022，28（17）：1-8.

柳荣，杨霞，高艳奎，等.加味葛根芩连汤对2型糖尿病db/db小鼠胰腺组织TGR5/cAMP/GLP-1信号通路的影响［J］.中国实验方剂学杂志，2023，29（4）：25-32.

MARLET I R， ÖLMESTIG J N E， VILSBØLL T， et al. Neuroprotective mechanisms of glucagon-like peptide-1-based therapies in ischaemic stroke：A systematic review based on pre-clinical studies ［J］. Basic Clin Pharmacol Toxicol， 2018， 122（6）： 559-569.

MASKERY M P，HOLSCHER C，JONES S P，et al.Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke：A systematic scoping review［J］.J Cereb Blood Flow Metab，2021，41（1）：14-30.

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