Therapeutic effect of astragaloside-IV on bradycardia is involved in up-regulating klotho expression

AimsIn order to determine whether klotho is involved in the therapeutic effects of Astragaloside-IV on bradycardia, we evaluated the effect of ASG-IV on klotho and the effect of klotho on HCN4 and If.Main methodsAdministrating isoproterenol (5mg/kg) for 15 days to establish a rat bradycardia model randomized SD rats into control, model (ISO) and ASG-IV (5 mg/kg/day) groups to explore the effect of ASG-IV on klotho. Rats were sacrificed on day15 after heart rate and heart function were measured; SAN tissues were collected to measure the expression of klotho and HCN4. In vitro, neonatal rat myocardial cells were incubated with LPS for 24 h to inhibit the expression of HCN4 and incubated with LPS + klotho to explore the effect of klotho on HCN4 expression. We also adopted full-patch-clamp technique to explore the effect of klotho on If.Key findingsHeart rate in model group was significantly decreased (356.6 ± 19.7 vs. 428.9 ± 19.9 in control group, P < 0.01) and ASG-IV can increase heart rate (401.4 ± 12.0 vs. 356.6 ± 19.7 in model group, P < 0.01). The expression of klotho was also up-regulated (P < 0.05). In vitro, after incubation with LPS for 24 h, HCN4 expression was significantly decreased in neonatal rat myocardial cells (0.6 ± 0.07 vs. 1.0, P < 0.01) and If was significantly declined. Exogenous klotho showed protective effect on HCN4 expression (1.58 ± 0.16 in ASG-IV group vs. 0.6 ± 0.07 in LPS group, P < 0.05) and If.SignificanceKlotho is involved in the treatment mechanism of ASG-IV.

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