期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 22, 期 6, 页码 3058-3072出版社
WILEY
DOI: 10.1111/jcmm.13557
关键词
myeloid differentiation factor 88; myocardial infarction; nuclear factor-kappaB; tanshinone IIA; toll-like receptor 4; ventricular remodelling
资金
- National Natural Science Foundation of China [30950031, 81171012, 81271225, 81400902, 81570531, 81571055, 81672731]
- Cultivate National Science Fund for Distinguished Young Scholars of Jiangsu Normal University
- Qinglan Project of the Young and Middle-aged Academic Leader of Jiangsu College and University
- 333 Project Award of Jiangsu Province
- Major Fundamental Research Program of the Natural Science Foundation of the Jiangsu Higher Education Institutions of China [13KJA180001]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
In this study, we aim to investigate the role of tanshinone IIA in myocardial infarction (MI), especially in left ventricular remodelling (VR) and the underlying mechanism involving the TLR4/MyD88/NF-kappa B signalling pathway. Sprague-Dawley (SD) rats (n = 96) were selected, and 12 of them underwent sham surgery. The remaining 84 rats were subjected to MI modelling. HE and MT staining were carried out to estimate infract size, histopathological changes and fibrosis degree. Macrophage infiltration and cardiomyocyte apoptosis were evaluated by immunohistochemistry and TUNEL staining. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to determine the expression levels of TLR4, MyD88 and NF-kappa B. Serum levels of IL-2, IL-6, IL-8, TNF-a, procollagen I Cpropeptide (PICP), and procollagen III N-propeptide (PIIINP) were measured using enzyme-linked immunosorbent assay (ELISA). The heart weight/body weight, mean arterial pressure (MAP), left ventricular end-systolic pressure (LVESP), +dP/dt and -dP/dt increased while the ventricular function and the left ventricular end-diastole pressure (LVEDP) decreased in MI rats. Compared with the rats undergoing sham surgery, MI rats showed larger infarct size, severer fibrosis, higher expression levels of TLR4, NF-B-P65, MyD88, IL-2, IL-6, IL-8, TNF-a, PICP and PIIINP as well as enhanced macrophage infiltration, cardiomyocyte apoptosis. After treatment with tanshinone IIA combined with LPS for 4 weeks, the rats showed better condition than those treated with only LPS. These results indicate that tanshinone IIA attenuates MI and prevents left VR. Importantly, inhibition of TLR4/MyD88/NF-kappa B signalling pathway is a key step in this process.
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