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| 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 |
| Department of Emergency, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200437, China |
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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.
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Corresponding Authors:
Zhao Lei, E-mail:smieqian1975@qq.com
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