Salidroside Mitigates Sepsis-Induced Myocarditis in Rats by Regulating IGF-1/PI3K/Akt/GSK-3β Signaling
Sepsis-induced myocardial injury (SIMI) is caused by various mechanisms. The aim of this study was to investigate the effects of salidroside (Sal) on SIMI and its mechanisms in rats. The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) (15 mg/kg in sterile saline). Sal decreased the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), whereas the expressions of insulin-like growth factor-1 (IGF-1) signaling-related proteins, such as IGF-1 and its corresponding receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3K), p-PI3K, Akt, p-Akt, and glycogen synthase kinase-3β (GSK-3β), in the heart were decreased with Sal pretreatment. Mitigated myocardial cell swelling, degeneration, loss of transverse striations, and inflammatory cell infiltration were also observed in the LPS + Sal groups. Thus, Sal is assumed to exert pronounced cardioprotective effects in rats subjected to LPS, probably through regulation of IGF-1/PI3K/Akt/GSK-3β signaling.
KEY WORDSsalidroside sepsis myocardial inflammation IGF-I/PI3K/Akt/GSK-3β signaling
This work was supported by the National Twelve Five Major Drug Discovery Project (2011ZX09102-002-01).
- 7.Wang, Y., N. Ahmad, M.A. Wani, and M. Ashraf. 2004. Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis. Journal of Molecular and Cellular Cardiology 37: 1041e52.Google Scholar
- 8.Li, Q., B. Li, X. Wang, A. Leri, K.P. Jana, Y. Liu, et al. 1997. Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. The Journal of Clinical Investigation 100: 1991e9.Google Scholar
- 17.Yan, T.H., Y. Ma, W. Yang, et al. 2009. Protective effects of salidroside on acute myocardial ischemia of rats and neonatal rat cardiocytes. Lishizhen Medicine and Materia Medica Research 20: 693–695.Google Scholar
- 23.Rong, S.L., Y.J. Wang, X.L. Wang, et al. 2010. Recombinant proteins secreted from tissue-engineered bioartificial muscle improve cardiac dysfunction and suppress cardiomyocyte apoptosis in rats with heart failure. Chinese Medical Journal 123: 2633–3626.Google Scholar
- 26.Metsuzaki, H., M. Tamatani, N. Mistuda, et al. 2004. Activation Akt kinase inhibits apoptosis and changes in bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons. Journal of Neurochemistry 73: 2037–2046.Google Scholar