Abstract: BACKGROUND: Previous studies have shown that salidroside has an ameliorative effect on multi-organ fibrosis. However, the protective effect of salidroside on angiotensin ii-induced fibrosis in cardiac fibroblasts is unclear.
OBJECTIVE: To investigate the protective effects of salidroside on angiotensin ii-induced oxidative stress and extracellular matrix deposition in cardiac fibroblasts of Sprague-Dawley rats and its mechanism of action.
METHODS: Angiotensin II was used to induce fibrosis in cardiac fibroblasts, and there were five experimental groups: normal control group, model group (final concentration of angiotensin II in culture medium was 1 μmol/L), salidroside low and high dose groups (treatment with salidroside 50, 100 μmol/L for 2 hours, followed by co-incubation with angiotensin II for 48 hours), SIRT1 inhibitor group (treatment with SIRT1 inhibitor EX527 10 μmol/L for 2 hours, followed by high dose of salidroside for 2 hours and then co-incubation with angiotensin II for 48 hours). The cell viability was detected using the cell counting kit-8 method, the cell migration rate was detected by Transwell, the intracellular reactive oxygen species level was detected by DCFH-DA fluorescent probe, and the intracellular malondialdehyde content, superoxide dismutase and catalase activities were detected by relevant kits. The protein and mRNA expression levels of SIRT1, LOXL2, α-SMA, type I collagen and type III collagen were detected by western blot and qRT-PCR, respectively.
RESULTS AND CONCLUSION: The cells were identified as cardiac fibroblasts by Vimentin fluorescence. Compared with the normal control group, cell viability, cell migration rate, reactive oxygen species level, and malondialdehyde content were significantly increased, superoxide dismutase and catalase activities were significantly decreased, LOXL2, α-SMA, type I collagen, type III collagen mRNA and protein expression were significantly increased, and SIRT1 protein expression level was significantly decreased in the model group (all P < 0.01). Compared with the model group, the above indexes showed opposite changes in the salidroside low and high dose groups (all P < 0.05). Moreover, salidroside showed dose-dependent regulation. Compared with salidroside groups, cell migration rate and α-SMA protein expression level were significantly increased in the SIRT1 inhibitor group (both P < 0.001). To conclude, salidroside has a protective effect on angiotensin II-induced cardiac fibroblasts and can dose-dependently inhibit oxidative stress and extracellular matrix deposition.

Key words: salidroside, angiotensin II, cardiac fibroblast, oxidative stress, fibrosis