Improvement effect and mechanism of circular RNA SORBS2 on myocardial injury in septic mice
YUAN Yuan
LIU Xiaoxian
LONG Su
YANG Guohui
TANG Nana
NING Rui
FANG Hao
OU Jing
WU Xi
LI Ziwei
Abstract：Objective To observe the effect of circular RNA SORBS2(circSORBS2)on myocardial injury in septic mice and to explore its mechanism.Methods Forty-eight SPF C57BL/6J male mice were randomly divided into Sham group,model group,sh-NC group and sh-circSORBS2 group,with 12 mice in each group.The mice in the model group,sh-NC group and sh-circSORBS2 group were treated with cecal ligation(CLP)to construct the mouse models of sepsis-in-duced myocardial injury.Mice in the sh-NC group and sh-circSORBS2 group were intravenously injected with sh-NC(neg-ative control)or sh-circSORBS2(silencing circSORBS2 expression)adeno-associated virus vector particles one week be-fore CLP.In the Sham group,only laparotomy and abdominal closure were performed without ligation and puncture of the cecum,and no tail vein injection was performed.After the mouse models were completed,the survival rate,myocardial histopathology,cardiac function indexes[left ventricular systolic pressure(LVSP),maximum rate of left ventricular pres-sure increase(+dp/dtmax),maximum rate of left ventricular pressure decrease(-dp/dtmax),left ventricular end-diastolic pressure(LVEDP),creatine kinase isoenzyme MB(CK-MB),and cardiac troponin I(cTnI)],myocardial tissue inflam-matory factors[tumor necrosis factor(TNF)-α and interleukin-6(IL-6)],myocardial tissue pyroptosis-related factors[NOD-like receptor hot protein domain-related protein 3(NLRP3),caspase-1(Caspase-1),IL-1β,and Gasdermin D(GSDMD)],and the relative expression levels of circRBSSO2,miR-21-3 p,and Sma/MAD-related protein 7(SMAD7)mRNA in the myocardial tissues of mice in each group were observed and compared.The targeting relationship of circ-SORBS2,miR-21-3 p and SMAD7 was predicted by starBase target gene prediction website,and verified by luciferase re-porter gene experiment.Results Compared with the Sham group,the survival rate,LVSP,+dp/dtmax,and miR-21-3p decreased,while LVEDP,-dp/dtmax,cTnI,CK-MB,TNF-α,IL-6,NLRP3,Caspase-1,IL-1β,GSDMD,circSORBS2,and SMAD7 mRNA increased(all P<0.05),and myocardial necrosis occurred in the model group.Compared with the sh-NC group,the survival rate,LVSP,+dp/dtmax,and miR-21-3p increased,while LVEDP,-dp/dtmax,cTnI,CK-MB,TNF-α,IL-6,NLRP3,Caspase-1,IL-1β,GSDMD,circSORBS2,and SMAD7 mRNA decreased(all P<0.05),and the degree of myocardial injury was alleviated in the sh-circSORBS2 group.The results of the dual-luciferase reporter gene assay showed that circSORBS2 targetedly regulated miR-21-3p,and miR-21-3p regulated SMAD7.Conclusion Inhibition of circSORBS2 expression can alleviate myocardial injury in septic mice,and the mechanism may be related to circSORBS2 relieving the inhibition of SMAD7 by adsorbing miR-21-3p.
Keywords：circular RNA SORBS2microRNA-21-3psepsismyocardial injurypyroptosis
Publication Date：2026-01-25
Online Publishing Date：2026-03-05(First online date of this platform, not the publication date of the document)
Pages：6( 60-65 )