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Effect of resveratrol on cardiac function in mice with dilated cardiomyopathy by adjusting the RIP1/RIP3/MLKL pathway
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DOI   10.11656/j.issn.1672-1519.2026.05.09
Key Words   resveratrol;RIP1/RIP3/MLKL pathway;dilated cardiomyopathy;cardiac function
Author NameAffiliationE-mail
RAO Xidong Hubei Provincial Hospital of Traditional Chinese Medicine(Affiliated Hospital of Hubei University of Chinese Medicine), Wuhan 430070, China  
ZHU Hongfei Hubei Provincial Hospital of Traditional Chinese Medicine(Affiliated Hospital of Hubei University of Chinese Medicine), Wuhan 430070, China  
WU Meijiao Hubei Provincial Hospital of Traditional Chinese Medicine(Affiliated Hospital of Hubei University of Chinese Medicine), Wuhan 430070, China wumeijiao@hbhtcm.hbhtcm.edu.cn 
Abstract
    [Objective] To discuss the effect of resveratrol(RSV) on cardiac function in mice with dilated cardiomyopathy(DCM) by adjusting the Receptor-Interacting Serine/Threonine-Protein Kinase(RIP)1/RIP3/Mixed Lineage Kinase Domain-Like Pseudokinase(MLKL) pathway. [Methods] Male C57BL/6J mice were injected with doxorubicin to induce DCM model. Mice were stochastically separated into Control group,DCM group,DCM+RSV group,DCM+Tumor Necrosis Factor-alpha(TNF-α) group,and DCM+RSV+TNF-α group. Echocardiography was used to evaluate the cardiac function of mice in each group. ELISA was used to detect serum myocardial injury indicators of mice. HE,Masson,and DAPI propidium iodide(PI) stainings were used to observe pathological myocardial injury in mice. Immunohistochemistry was used to measure fibrosis related proteins in the myocardium of mice in each group. In addition,Western blot was used to measure the RIP1/RIP3/MLKL pathway related proteins of mice. [Results] Compared with the Control group,the DCM group showed increases in mouse heart weight,heart weight/body weight ratio,left ventricular end-diastolic diameter(LVEDD),creatine kinase-myocardial band(CK-MB),cardiac troponin t(cTn-T),B-type Natriuretic Peptide(BNP),monocyte chemoattractant protein-1(MCP-1),fibrous tissue deposition,collagen deposition,PI positivity rate,alpha-smooth muscle actin(α-SMA),collagen type Ⅲ(Collagen Ⅲ),TNF-α,p-RIP1/RIP1,p-RIP3/RIP3,and p-MLKL/MLKL,and decreases in left ventricular shortening fraction(LVSF),left ventricular ejection fraction(LVEF),and heme oxygenase-1(HO-1)(P<0.05). Compared with the DCM group or DCM+RSV+TNF-α group,the DCM+RSV group showed decreases in mouse heart weight,heart weight/body weight ratio,LVEDD,CK-MB,cTn-T,BNP,MCP-1,fibrous tissue deposition,collagen deposition,PI positivity rate,α-SMA,Collagen Ⅲ,TNF-α,p-RIP1/RIP1,p-RIP3/RIP3,and p-MLKL/MLKL,and increases in LVSF,LVEF,and HO-1(P<0.05);the DCM+TNF-α group showed increases in mouse heart weight,heart weight/body weight ratio,LVEDD,CK-MB,cTn-T,BNP,MCP-1,fibrous tissue deposition,collagen deposition,PI positivity rate,α-SMA,Collagen Ⅲ,TNF-α,p-RIP1/RIP1,p-RIP3/RIP3,and p-MLKL/MLKL,and decreases in LVSF,LVEF,and HO-1(P<0.05). [Conclusion] RSV effectively improves myocardial fibrosis and enhances cardiac function in DCM mice by inhibiting the RIP1/RIP3/MLKL pathway.

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