Zuogui Jiangtang Shuxin Prescription Ameliorates Lipid Deposition in Diabetic Cardiomyopathy of MKR Mice by Regulating AMPK/FoxO1/CD36 Signaling Pathway
10.13422/j.cnki.syfjx.20252506
- VernacularTitle:左归降糖舒心方通过调控AMPK/FoxO1/CD36信号通路改善MKR小鼠糖尿病心肌病脂质沉积
- Author:
Xiu LIU
1
;
Juping WANG
1
;
Jiawang HUANG
1
;
Junju ZOU
1
;
Qin XIANG
1
;
Yunfeng YU
1
;
Rong YU
1
Author Information
1. Hunan University of Chinese Medicine，Changsha 410208， China
- Publication Type:Journal Article
- Keywords:
Zuogui Jiangtang Shuxin prescription;
diabetic cardiomyopathy;
MKR mice;
adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(10):134-142
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription （ZJSP） on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy （DCM）， with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin （STZ） while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group， the low-dose（14.43 g·kg-1）and high-dose（28.86 g·kg-1） ZJSP groups， and the metformin group （0.25 g·kg-1）， with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks， fasting blood glucose （FBG） and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin （FINS） and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin （HE） staining， and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of AMPK， FoxO1， and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK， p-AMPK， FoxO1， p-FoxO1， and CD36. ResultsCompared with the control group， the model group showed significantly increased levels of FBG and FINS （P<0.01）， elevated levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.01）， and significantly decreased left ventricular ejection fraction （EF） and fractional shortening （FS） values （P<0.01）. HE staining revealed marked cardiomyocyte hypertrophy， disarray， and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased， while FoxO1 and CD36 mRNA expressions were significantly increased （P<0.01）. The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced， while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased （P<0.01）. Compared with the model group， all treatment groups exhibited significantly reduced FBG （P<0.01）， decreased FINS and blood lipid levels （TG， TC， LDL-C） （P<0.05， P<0.01）， improved cardiac function （P<0.05）， noticeable amelioration of myocardial histopathological morphology and lipid deposition， increased AMPK mRNA expression （P<0.01）， with significantly downregulated FoxO1 and CD36 mRNA expressions （P<0.01）， elevated p-AMPK/AMPK protein expression levels in myocardial tissue （P<0.05）， significantly decreased p-FoxO1/FoxO1 ratios （P<0.01）， and downregulated CD36 protein expression levels （P<0.05， P<0.01）. ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice， and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.
