To investigate the mechanism underlying the protective effect of miRNA-146a on myocardial ischemia in sepsis by regulating TLR-4/NF-κB pathway
Guo Jian
Hu Guan-yu
Qian Yi-ming
Qian Feng-hua
Shen Meng-wen
Zhao Lei
Abstract：Objective To investigate the mechanism underlying the protective effect of miRNA-146a on myocardial ischemia in sepsis by regulating TLR-4/NF-κB pathway.Methods Rat sepsis model was prepared by cecal ligation and puncture (CLP).Rats in miRNA-146a inhibitor group were intravenously injected with miRNA-146a antagomir 24 h before the operation;rats in miRNA-146a agonist group were intravenous injection with miRNA-146a agomir 24 h before the operation;rats in Shengjiangsan group were gavaged Shengjiangsan 12 h after the operation at a dosage of 2.0 g/kg.The ultrastructure of the heart was studied by light microscopy;the expressions of cTnI,BNP,TLR-4,NF-κB,miRNA-146a and TNF-α mRNA in 24 h,48 h and 72 h groups were observed.Results The expression of miRNA-146a in the model group increased,48 h to peak,and then dropped,compared with the blank group,there was a statistically significant difference (P ＜ 0.001).The expression of miRNA-146a in the inhibitor group was lower than that in the model group at each time point (P ＜ 0.001).The expression of miRNA-146a in the agonist group was higher than that in the model group,and the expression of 24 h and 72 h increased (P ＜ 0.001).Compared with the model group,the expression of miRA-146a 48 h decreased (P ＜0.001)and 72 h increased (P ＜0.001) in Shengjiangsan group.In the model group,the expression of TLR-4 increased gradually,and the peak value of 72 h reached the peak value.Compared with the blank group,there were statistical differences at 3 time points (P ＜ 0.001).Compared with the model group,the expression of TLR-4 in the inhibitor group increased at each time node (P ＜ 0.001),the level of TLR-4 decreased in the agonist group at each time were(P ＜0.001),the level of TLR4 in Shengjiangsan group was decreased at each time node (P ＜0.001).In the model group,the expression of NF-κB increased gradually,and reached the peak valueof 72 h.Compared with the blank group,there were statistical differences between the 3 time nodes (P ＜ 0.001).Compared with the model group,the level of NF-κB in inhibitor group increased at each time node (P ＜ 0.001),the level of NF-κB in agonist group decreased at each time node (P ＜ 0.001),NF-κB level in Shengjiangsan group decreased at each time node (P ＜ 0.001).Conclusion miRNA-146a regulates TLR-4/NF-κB signaling pathway and downstream inflammatory factor TNF-α through negative feedback mechanism,which is an important signal transduction mechanism and key regulatory pathway in the pathogenesis of SMD.miRNA-146a can protect the myocardium of sepsis by regulating some effector molecules in the TLR-4/NF-κB signaling pathway.
Keywords：ShengjiangsanSepsisMyocardiummiRNA-146aTLR-4/NF-κB
Publication Date：2018-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 431-436,后插2 )