Objective To explore the synergic mechanism of ginsenoside Rg_(1)(Rg_(1))and aconitine(AC)by acting on normal neonatal rat cardiomyocytes(NRCMs)and pentobarbital sodium(PS)-induced damaged NRCMs.Methods The toxic,non-...Objective To explore the synergic mechanism of ginsenoside Rg_(1)(Rg_(1))and aconitine(AC)by acting on normal neonatal rat cardiomyocytes(NRCMs)and pentobarbital sodium(PS)-induced damaged NRCMs.Methods The toxic,non-toxic,and effective doses of AC and the most suitable compatibility concentration of Rg_(1) for both normal and damaged NRCMs exposed for 1 h were filtered out by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide,respectively.Then,normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg_(1) for 1 h,and the cellular activity,cellular ultrastructure,apoptosis,leakage of acid phosphatase(ACP)and lactate dehydrogenase(LDH),intracellular sodium ions[Na^(+)],potassium ions[K^(+)]and calcium ions[Ca^(2+)]levels,and Nav1.5,Kv4.2,and RyR_(2) genes expressions in each group were examined.Results For normal NRCMs,3000µmol/L AC significantly inhibited cell viability(P<0.01),promoted cell apoptosis,and damaged cell structures(P<0.05),while other doses of AC lower than 3000µmol/L and the combinations of AC and Rg_(1) had little toxicity on NRCMs.Compared with AC acting on NRCMs alone,the co-treatment of 3000 and 10µmol/L AC with 1µmol/L Rg_(1) significantly decreased the level of intracellular Ca^(2+)(P<0.01 or P<0.05),and the co-treatment of 3000µmol/L AC with 1µmol/L Rg_(1) significantly decreased the level of intracellular Ca^(2+)via regulating Nav1.5,RyR_(2) expression(P<0.01).For damaged NRCMs,1500µmol/L AC aggravated cell damage(P<0.01),and 0.1 and 0.001µmol/L AC showed moderate protective effect.Compared with AC used alone,the co-treatment of Rg_(1) with AC reduced the cell damage,0.1µmol/L AC with 1µmol/L Rg_(1) significantly inhibited the level of intracellular Na+(P<0.05),1500µmol/L AC with 1µmol/L Rg_(1) significantly inhibited the level of intracellular K+(P<0.01)via regulating Nav1.5,Kv4.2,RyR_(2) expressions in impaired NRCMs.Conclusion Rg_(1) inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of[Na^(+)],[K^(+)],and[Ca^(2+)].展开更多
基金Supported by the National Natural Science Foundation of China(Nos.81630101 and 81891012)Department of Science and Technology of Sichuan Province(No.2018JZ0081)+1 种基金the Open Research Fund of Chengdu University of Traditional Chinese Medicine Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China(No.2020XSGG001)Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province(No.20ZYKJCX0006)。
文摘Objective To explore the synergic mechanism of ginsenoside Rg_(1)(Rg_(1))and aconitine(AC)by acting on normal neonatal rat cardiomyocytes(NRCMs)and pentobarbital sodium(PS)-induced damaged NRCMs.Methods The toxic,non-toxic,and effective doses of AC and the most suitable compatibility concentration of Rg_(1) for both normal and damaged NRCMs exposed for 1 h were filtered out by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide,respectively.Then,normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg_(1) for 1 h,and the cellular activity,cellular ultrastructure,apoptosis,leakage of acid phosphatase(ACP)and lactate dehydrogenase(LDH),intracellular sodium ions[Na^(+)],potassium ions[K^(+)]and calcium ions[Ca^(2+)]levels,and Nav1.5,Kv4.2,and RyR_(2) genes expressions in each group were examined.Results For normal NRCMs,3000µmol/L AC significantly inhibited cell viability(P<0.01),promoted cell apoptosis,and damaged cell structures(P<0.05),while other doses of AC lower than 3000µmol/L and the combinations of AC and Rg_(1) had little toxicity on NRCMs.Compared with AC acting on NRCMs alone,the co-treatment of 3000 and 10µmol/L AC with 1µmol/L Rg_(1) significantly decreased the level of intracellular Ca^(2+)(P<0.01 or P<0.05),and the co-treatment of 3000µmol/L AC with 1µmol/L Rg_(1) significantly decreased the level of intracellular Ca^(2+)via regulating Nav1.5,RyR_(2) expression(P<0.01).For damaged NRCMs,1500µmol/L AC aggravated cell damage(P<0.01),and 0.1 and 0.001µmol/L AC showed moderate protective effect.Compared with AC used alone,the co-treatment of Rg_(1) with AC reduced the cell damage,0.1µmol/L AC with 1µmol/L Rg_(1) significantly inhibited the level of intracellular Na+(P<0.05),1500µmol/L AC with 1µmol/L Rg_(1) significantly inhibited the level of intracellular K+(P<0.01)via regulating Nav1.5,Kv4.2,RyR_(2) expressions in impaired NRCMs.Conclusion Rg_(1) inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of[Na^(+)],[K^(+)],and[Ca^(2+)].
