Effect of Phloretin on Rats Ischemia-reperfusion Myocardial Injury by Regulating the Shh/Gli1 Signaling Pathway
ZHANG Zhiling
DI Xueqin
MA Xiaoru
MA Shuyi
LI Fangfang
Abstract：Objective:To explore the effect of phloretin(Pht)on rats ischemia-reperfusion myocardial injury(MIRI)by regulating the sonic hedgehog/glioma-associated oncogene 1(Shh/Gli1)signaling pathway.Methods:A total of 90 healthy male SD rats of specific pathogen-free(SPF)grade were randomly divided into the control group(Control group),the model group(MIRI group),the low-dose phytol treatment group(Pht-L),the high-dose phytol treatment group(Pht-H),and the high-dose phytol treatment+cyclopamine(a Gli1/Shh signaling pathway inhibitor)group(Pht-H+Cyc group).The MIRI rat model was established by ligating the left anterior descending branch of the coronary artery.The levels of serum inflammatory factors such as tumor necrosis factor(TNF-α),interleukin-1β(IL-1β),and myocardial injury indicators such as creatine kinase isoenzyme(CK-MB),troponin I(cTnI),and myoglobin(Mb)were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the morphological changes of myocardial tissue.terminal deoxyribonucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)staining was used to detect the apoptosis of cardiac muscle cells.The expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),Shh and Gli1 were detected by Western Blot.Results:Compared with the Control group,the MIRI group showed deep staining of myocardial cell nuclei,disordered arrangement of myocardial fibers,and significant infiltration of inflammatory cells,the levels of TNF-α,IL-1β,CK-MB,cTnI,Mb,TUNEL positive cells,apoptosis rate,and Bax expression elevated,the expression of Bcl-2,Shh,and Gli1 decreased(P＜0.05).The myocardial cells in the Pht-L and Pht-H groups were relatively intact and normal compared that of the MIRI group,with relatively neat arrangement of myocardial fibers and less obvious infiltration of inflammatory cells,the levels of TNF-α,IL-1β,CK-MB,cTnI,Mb,TUNEL positive cells,cell apoptosis rate,and Bax expression reduced,the expression of Bcl-2,Shh,and Gli1 increased(P＜0.05).The Pht-H+Cyc group showed more severe myocardial tissue damage compared that of the Pht-H group,the levels of TNF-α,IL-1β,CK-MB,cTnI,Mb,TUNEL positive cells,apoptosis rate,and Bax expression elevated,the expression of Bcl-2,Shh,and Gli1 decreased(P＜0.05).Conclusion:Phloretin can reduce myocardial injury in rats with myocardial ischemia-reperfusion injury,and its mechanism is related to the activation of the Shh/Gli1 signaling pathway.
Keywords：myocardial ischemia-reperfusion injuryphloretinsonic hedgehog/glioma-associated oncogene 1 signaling pathwayexperimental study
Publication Date：2025-09-10
Online Publishing Date：2025-09-18(First online date of this platform, not the publication date of the document)
Pages：6( 2617-2622 )