title: Therapeutic effect of astragaloside-IV on bradycardia is involved in up-regulating klotho expression.
abstract: OBJECTIVE
  In 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.
  
  
  METHODS
  Administrating isoproterenol (5 mg/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 day 15 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.
  
  
  RESULTS
  Heart 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 24h, 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.
  
  
  CONCLUSIONS
  Klotho is involved in the treatment mechanism of ASG-IV.
authors.affiliation: China Pharmaceutical University, China; Hebei General Hospital, China.
authors.forename: Xuejia
authors.initials: X
authors.lastname: Qiu
authors.affiliation: China Pharmaceutical University, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Guo
authors.affiliation: China Pharmaceutical University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: China Pharmaceutical University, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.affiliation: China Pharmaceutical University, China. Electronic address: tyq@cpu.edu.cn.
authors.forename: Yi-qun
authors.initials: YQ
authors.lastname: Tang
mesh_terms: D000318:Adrenergic beta-Agonists; D000818:Animals; D000831:Animals, Newborn; D001919:Bradycardia / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics*; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics*; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000096:biosynthesis / Q000235:genetics; D007545:Isoproterenol; D000090265:Klotho Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; C513836:HCN4 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008070:Lipopolysaccharides; D015221:Potassium Channels; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D005966:Glucuronidase; D000090265:Klotho Proteins; D007545:Isoproterenol
keywords: Astragaloside IV; Bradycardia; HCN4; ISO; Klotho