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Panminerva Medica 2020 Jun 02

DOI: 10.23736/S0031-0808.20.03937-3


lingua: Inglese

Protein kinase TBK1 / IKKε inhibitor Amlexanox improves cardiac function after acute myocardial infarction in rats

Changgan MO 1, 2, Hui HA 2, Xiuge TANG 2, Xinxu LU 2, Yin WEI 2, Dan LUO 2, Zhuodong ZHOU 2

1 Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, China; 2 Department of Cardiology, The People’s Hospital of Hechi, Hechi, China


BACKGROUND: To study the effect of protein kinase TBK1 and IKKε inhibitor Amlexanox on cardiac function after acute myocardial infarction (AMI) in rats.
METHODS: AMI model was established in rats. Experimental grouping: sham + dimethyl sulfoxide (DMSO) group, sham + Amlexanox group, AMI + DMSO group, AMI + Amlexanox group. 12 h after surgery, rats in the sham + Amlexanox group and AMI + Amlexanox group were given an intraperitoneal injection of Amlexanox at a dose of 25 mg / kg once a day for 7 consecutive days. The sham + DMSO group and the AMI + DMSO group were given the same amount of DMSO as a control. Ultrasound was used to detect changes in cardiac function in rats for 3 and 7 days after continuous administration, and RT-PCR was used to detect the transcription levels of ISGs and apoptosis in myocardial tissue. HE and immunohistochemical staining were used to observe the inflammatory cell infiltration level and MOMA2 expression in myocardial tissue. Western blot was used to examine the TBK1 signaling pathway and its downstream protein expression.
RESULTS: Amlexanox can improve left ventricular ejection fraction (LVEF) and short-axis shortening rate (FS) after AMI in rats, reduce remodeling of cardiomyopathy, and reduce inflammatory cell infiltration, thus reducing myocardial apoptosis.
CONCLUSIONS: The protein kinases TBK1 and IKKε inhibitor Amlexanox can improve cardiac function in rats after AMI, reduce myocardial inflammatory response, reduce myocardial apoptosis, and then exert myocardial protection in vivo.

KEY WORDS: Amlexanox; TBK1 / IKKε; Acute myocardial infarction; Inflammatory response; Cardiac function

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