期刊
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
卷 71, 期 2, 页码 289-299出版社
SPRINGER
DOI: 10.1007/s13105-015-0412-1
关键词
Cholecalciferol; mRNA; NF-kappa B-p65/I kappa B-alpha signaling; Cardiac hypertrophy; Rats
资金
- Research Center of the Female Scientific and Medical Colleges, Deanship of Scientific Research, King Saud University
A growing body of evidence suggests that immune activation and inflammatory mediators may play a key role in the development and progression of left ventricle (LV) hypertrophy. The present study was designed to test the hypothesis that the cardioprotective effect of cholecalciferol (Vit-D3) is mediated via the regulation of messenger RNA (mRNA) expression of pro-inflammatory cytokines. Rats were randomly divided into four groups: control group received normal saline (0.9 % NaCl) i.p. for 14 days; Vit-D3 group received Vit-D3 at a dose of 12 mu g/kg/day by gavage for 14 days; ISO group received saline for 7 days, and at day 7, ISO (5 mg/kg/day) was injected i.p. for 7 consecutive days to induce cardiac hypertrophy; and Vit-D3 + ISO group was treated with Vit-D3 for 14 days, and at day 7, ISO was administered for 7 consecutive days. Heart/body weight ratio, troponin-T, creatine kinase-MB, and tumor necrosis factor-alpha (TNF-alpha) levels of LV tissue were estimated. Levels of mRNA expression of NF-(DB)-B-0 (NF-(DB)-B-0)/p65 and inhibitory kappa B ((IDB)-B-0)-alpha were determined by real-time PCR. Vit-D3 administration before and during induction of cardiac hypertrophy significantly reduced (P < 0.001) cardiac biomarkers. The histopathological examination further confirmed these results. In addition, Vit-D3 significantly decreased (P < 0.001) NF-(DB)-B-0-p65 mRNA expression and increased (P < 0.01) (IDB)-B-0-alpha mRNA expression in LV tissues compared to ISO group. Based on these findings, it was concluded that the administration of cholecalciferol markedly attenuated the development of ISO-induced cardiac hypertrophy likely through downregulation of TNF-alpha /NF-D(0)b/p65 signaling pathways. However, it should be pointed out that other signaling pathways may contribute to the cardioprotective effect of Vit-D3 which requires further investigation.
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