Improvement effect and mechanism of TLR4 inhibitor pretreatment on myocardial injury in septic cardiomyopathy mice
Chen Shiyang
Wang Xiaojing
Dong Yujie
Zhang Meichun
Abstract：Objective To explore the improvement effect and possible mechanismof Toll like receptor4(TLR-4)in-hibitors on lipopolysaccharide(LPS)induced myocardial injury in septic cardiomyopathy(SIC)mice.Methods The experi-ment will be conducted at the Animal Experiment Center of Wuhan University of Science and Technology from March to June 2023.Nine SPF grade male C57BL/6 mice were randomly divided into a control group,SIC group,and TLR4 inhibitor in-tervention group(intervention group)using a random number table method,with three mice in each group.The SIC group was injected intraperitoneally with LPS(15 mg/kg)to construct a SIC mouse model.The intervention group received pre-treatment with TLR4 inhibitors at a rate of 0.3 mg·kg-1·h-1 via the tail vein 1 hour before constructing the SIC mouse model.The control group was intraperitoneally injected with physiological saline(15 mg/kg).After 24 hours of modeling,the mice were euthanized and their hearts were collected.Hematoxylin eosin(HE)staining was used to observe the pathological changes in the myocardial tissue of the mice.Enzyme linked immunosorbent assay(ELISA)was used to determine serum troponin(cTnI),creatine kinase isoenzyme(CK-MB),plasma brain natriuretic peptide(BNP),and tumor necrosis factor α(TNF-α),Interleukin-6 and IL-1 βin each group of mice.Detection protein expression status of TLR4 and NF κ B by West-ern Blot.Results The myocardial cell structure in the control group was normal;The arrangement of myocardial fibers in the SIC group was disordered,with some myocardial cells showing edema and obvious inflammatory cell infiltration in the interstitium;The intervention group had relatively intact tissue morphology and structure,with regular arrangement of myo-cardial fibers and scattered inflammatory cell infiltration in the interstitium.Mouse myocardial injury markers cTnI,CK-MB,BNP:SIC group>intervention group>control group(F=437.637,631.009,378.443,P<0.001);Inflammatory factor TNF-α,IL-1 β,IL-6 expression:SIC group>intervention group>control group(F=546.621,329.266,665.091,all P<0.001);TLR4 protein expression level:SIC group>control group>intervention group(F=388.491,P<0.001),NF-κ B protein expression level:SIC group>intervention group>control group(F=77.421,P<0.001).Further correlation analysis revealed the inflam-matory factor TNF-α,IL-1β,IL-6 levels and TLR4,NF-κB were positively correlated(r=0.990,0.988,0.994,0.976,0.981,0.971,all P<0.001).Conclusion TLR4 inhibitors can downregulate TLR4/NF-κ The B signaling pathway reduces inflamma-tory response in septic cardiomyopathy mice and improves myocardial injury in SIC mice.
Keywords：Sepsis-induced cardiomyopathyToll-like receptor 4Nuclear factor-κBMechanismMice
Publication Date：2024-01-18
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 99-103,105 )