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

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. Administrating isoproterenol (5mg/kg) for 15days to establish a rat bradycardia model randomized SD rat...

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Veröffentlicht in:Life sciences (1973) 2016-01, Vol.144, p.94-102
Hauptverfasser: Qiu, Xuejia, Guo, Qiao, Xiong, Wei, Yang, Xia, Tang, Yi-qun
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container_title Life sciences (1973)
container_volume 144
creator Qiu, Xuejia
Guo, Qiao
Xiong, Wei
Yang, Xia
Tang, Yi-qun
description 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. Administrating isoproterenol (5mg/kg) for 15days to establish a rat bradycardia model randomized SD rats into control, model (ISO) and ASG-IV (5mg/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 24h 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. Heart rate in model group was significantly decreased (356.6±19.7 vs. 428.9±19.9 in control group, P
doi_str_mv 10.1016/j.lfs.2015.11.021
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Administrating isoproterenol (5mg/kg) for 15days to establish a rat bradycardia model randomized SD rats into control, model (ISO) and ASG-IV (5mg/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 24h 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. Heart rate in model group was significantly decreased (356.6±19.7 vs. 428.9±19.9 in control group, P&lt;0.01) and ASG-IV can increase heart rate (401.4±12.0 vs. 356.6±19.7 in model group, P&lt;0.01). The expression of klotho was also up-regulated (P&lt;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&lt;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&lt;0.05) and If. Klotho is involved in the treatment mechanism of ASG-IV. 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Administrating isoproterenol (5mg/kg) for 15days to establish a rat bradycardia model randomized SD rats into control, model (ISO) and ASG-IV (5mg/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 24h 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. Heart rate in model group was significantly decreased (356.6±19.7 vs. 428.9±19.9 in control group, P&lt;0.01) and ASG-IV can increase heart rate (401.4±12.0 vs. 356.6±19.7 in model group, P&lt;0.01). The expression of klotho was also up-regulated (P&lt;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&lt;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&lt;0.05) and If. Klotho is involved in the treatment mechanism of ASG-IV. [Display omitted]</description><subject>Adrenergic beta-Agonists</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Astragaloside IV</subject><subject>Bradycardia</subject><subject>Bradycardia - chemically induced</subject><subject>Bradycardia - drug therapy</subject><subject>Bradycardia - genetics</subject><subject>Glucuronidase - biosynthesis</subject><subject>Glucuronidase - genetics</subject><subject>HCN4</subject><subject>Heart Function Tests</subject><subject>Heart Rate - drug effects</subject><subject>Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - biosynthesis</subject><subject>Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - genetics</subject><subject>ISO</subject><subject>Isoproterenol</subject><subject>Klotho</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Patch-Clamp Techniques</subject><subject>Potassium Channels - biosynthesis</subject><subject>Potassium Channels - genetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Saponins - pharmacology</subject><subject>Saponins - therapeutic use</subject><subject>Triterpenes - pharmacology</subject><subject>Triterpenes - therapeutic use</subject><subject>Up-Regulation - drug effects</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAURS0EotPCD2CDvGST4OePmIgVqgqtVInNiK31Jn6eesjEwU5G9N_jagpLVu8tzr3SPYy9A9GCgO7joR1DaaUA0wK0QsILtoFPtm9Ep-Al2wghdaOkMBfsspSDEMIYq16zC9mZXmkBG-a3D5RxpnWJA6cQaFh4ChzLknGPYyrRU3P3g6eJ7zL6xwGzj8hj4XE6pfFEvj58nZtM-3XEJU57_nNMy0Pi9HvOVEpM0xv2KuBY6O3zvWLbrzfb69vm_vu3u-sv982goV8ahVL4TsvQIyoMNijrvey990ETevDKkkYMO73rzFCnCOjRGjSopbWdumIfzrVzTr9WKos7xjLQOOJEaS0OrNFGKmt1ReGMDjmVkim4Occj5kcHwj25dQdX3bontw7AVbc18_65ft0dyf9L_JVZgc9ngOrGU6TsyhBpGsjHXL06n-J_6v8A0DyL2Q</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Qiu, Xuejia</creator><creator>Guo, Qiao</creator><creator>Xiong, Wei</creator><creator>Yang, Xia</creator><creator>Tang, Yi-qun</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20160101</creationdate><title>Therapeutic effect of astragaloside-IV on bradycardia is involved in up-regulating klotho expression</title><author>Qiu, Xuejia ; Guo, Qiao ; Xiong, Wei ; Yang, Xia ; Tang, Yi-qun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-3a20d642f9aa3af7f37dd29dddf4ead1d37e4aafb4b65c557019a75a5a427763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adrenergic beta-Agonists</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Astragaloside IV</topic><topic>Bradycardia</topic><topic>Bradycardia - chemically induced</topic><topic>Bradycardia - drug therapy</topic><topic>Bradycardia - genetics</topic><topic>Glucuronidase - biosynthesis</topic><topic>Glucuronidase - genetics</topic><topic>HCN4</topic><topic>Heart Function Tests</topic><topic>Heart Rate - drug effects</topic><topic>Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - biosynthesis</topic><topic>Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - genetics</topic><topic>ISO</topic><topic>Isoproterenol</topic><topic>Klotho</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Patch-Clamp Techniques</topic><topic>Potassium Channels - biosynthesis</topic><topic>Potassium Channels - genetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Saponins - pharmacology</topic><topic>Saponins - therapeutic use</topic><topic>Triterpenes - pharmacology</topic><topic>Triterpenes - therapeutic use</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qiu, Xuejia</creatorcontrib><creatorcontrib>Guo, Qiao</creatorcontrib><creatorcontrib>Xiong, Wei</creatorcontrib><creatorcontrib>Yang, Xia</creatorcontrib><creatorcontrib>Tang, Yi-qun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qiu, Xuejia</au><au>Guo, Qiao</au><au>Xiong, Wei</au><au>Yang, Xia</au><au>Tang, Yi-qun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic effect of astragaloside-IV on bradycardia is involved in up-regulating klotho expression</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>144</volume><spage>94</spage><epage>102</epage><pages>94-102</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>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. Administrating isoproterenol (5mg/kg) for 15days to establish a rat bradycardia model randomized SD rats into control, model (ISO) and ASG-IV (5mg/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 24h 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. Heart rate in model group was significantly decreased (356.6±19.7 vs. 428.9±19.9 in control group, P&lt;0.01) and ASG-IV can increase heart rate (401.4±12.0 vs. 356.6±19.7 in model group, P&lt;0.01). The expression of klotho was also up-regulated (P&lt;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&lt;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&lt;0.05) and If. Klotho is involved in the treatment mechanism of ASG-IV. [Display omitted]</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>26593401</pmid><doi>10.1016/j.lfs.2015.11.021</doi><tpages>9</tpages></addata></record>
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subjects Adrenergic beta-Agonists
Animals
Animals, Newborn
Astragaloside IV
Bradycardia
Bradycardia - chemically induced
Bradycardia - drug therapy
Bradycardia - genetics
Glucuronidase - biosynthesis
Glucuronidase - genetics
HCN4
Heart Function Tests
Heart Rate - drug effects
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - biosynthesis
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - genetics
ISO
Isoproterenol
Klotho
Lipopolysaccharides - pharmacology
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Patch-Clamp Techniques
Potassium Channels - biosynthesis
Potassium Channels - genetics
Rats
Rats, Sprague-Dawley
Saponins - pharmacology
Saponins - therapeutic use
Triterpenes - pharmacology
Triterpenes - therapeutic use
Up-Regulation - drug effects
title Therapeutic effect of astragaloside-IV on bradycardia is involved in up-regulating klotho expression
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