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- Title
TAK-242 Protects Against Apoptosis in Coronary Microembolization-Induced Myocardial Injury in Rats by Suppressing TLR4/NF-κB Signaling Pathway.
- Authors
Wang, Xian-tao; Lu, Yuan-xi; Sun, Yu-han; He, Wen-kai; Liang, Jia-bao; Li, Lang
- Abstract
Background/Aims: Myocardial apoptosis is heavily implicated in the myocardial injury caused by coronary microembolization (CME), and toll-like receptor 4 (TLR4) is considered to be involved in this apoptotic cascade. Therefore, the present study was designed to investigate the role of TLR4/NF-κB signaling pathway regulated by TAK-242, a selective TLR4 signal transduction inhibitor, in the myocardial apoptosis after CME in rats. Methods: Fortyfive rats were randomized (random number) into three groups: sham, CME and CME + TAK- 242 (n = 15 per group).CME was induced by injecting polyethylene microspheres (42μm) into the left ventricular except the sham group. CME + TAK-242 group was treated with TAK-242 (2mg/kg) via the tail vein 30 minutes before CME modeling. Cardiac function was evaluated 6 hours after operation. Tissue biopsy was stained with HBFP to measure the size of microinfarction area. TUNEL staining was used to detect myocardial apoptosis. Western blot and qPCR were used to evaluate the expression of TLR4, MyD88, NF-κB p65, p-IκBα and Cleaved caspase-3. Results: Cardiac function in the CME group and CME + TAK-242 group were significantly decreased compared with the sham group (P < 0.05) and the micro-infarction area, the apoptotic index, the expression of TLR4, NF-κB p65, p-IκBα and Cleaved caspase-3 were increased significantly (P < 0.05). Cardiac function in the CME + TAK-242 group was significantly improved compared with the CME group (P < 0.05) and the micro-infarction area, the apoptotic index, the expression of TLR4, MyD88, NF-κB p65, p-IκBα and Cleaved caspase-3 were decreased significantly (P < 0.05). Conclusions: TAK-242 can effectively improve CMEinduced cardiac dysfunction by regulating TLR4/NF-κB signaling pathway and then reducing the myocardial apoptosis.
- Subjects
APOPTOSIS; THERAPEUTIC embolization; MYOCARDIAL injury; TOLL-like receptors; CELLULAR signal transduction; LABORATORY rats
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2017, Vol 41, Issue 4, p1675
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000471248