In the state of acute myocardial ischemia,miRNA expression can regulate related genes and proteins,reduce myocardial cell damage,and thus play a protective role in the myocardium.However,the specific mechanism still n...In the state of acute myocardial ischemia,miRNA expression can regulate related genes and proteins,reduce myocardial cell damage,and thus play a protective role in the myocardium.However,the specific mechanism still needs to be further explored.Recent studies have found that the opening of the mitoKATP channel can regulate mitochondrial autophagy,and the initiation of miRNA-DNA methylation plays a regulatory role in inducing cell autophagy.The applicant research team previously found that Qishen Yiqi Dropping Pills could significantly improve myocardial ischemia by mediating MitokATP channels to regulate mitochondrial autophagy.,and animal experiments have confirmed that miR-155 plays a significant role in the aspect of autophagy regulates,inflammatory reaction and Vascular smooth muscle cell migration.Therefore,the applicant innovatively proposed that Qishen Yiqi Dropping Pills can regulate miRNA155-DNA methylation to mediate the opening of mitoKATP,thereby regulating mitochondrial autophagy and improving myocardial ischemia.In this paper,the association between mitochondrial autophagy and oxidative stress injury after myocardial ischemia was described,and the possible mechanism of Qisen Yiqi dropping pills regulating mitochondrial autophagy by regulating miRNA155-DNA methylation to mediate MitokATP to improve myocardial ischemia reperfusion injury was discussed,so as to provide theoretical ideas for related research.展开更多
Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases,including ischemia,heart failure,and hypertension.Under hypoxia,oxygen deficiency disrupts oxidative phosphorylation in mitochondria,impai...Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases,including ischemia,heart failure,and hypertension.Under hypoxia,oxygen deficiency disrupts oxidative phosphorylation in mitochondria,impairing ATP production and generating reactive oxygen species(ROS).These reactive species induce mitochondrial dysfunction,leading to oxidative stress,calcium imbalance,and activation of apoptosis pathways.The mitochondrial ATP-sensitive potassium channel(mitoKATP)and mitochondrial permeability transition pore(mPTP)channels are particularly affected,contributing to membrane potential loss,cytochrome c release,and cell death.This review delves into the molecular mechanisms underlying hypoxia-induced cardiovascular diseases,with a focus on mitochondrial impairment,ion channel dysfunction,and ROS overproduction.Additionally,we examine hypoxia-inducible factor 1-alpha(HIF-1α)as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress.Antioxidants and compounds modulating key ion channels,such as mitoKATP and mPTP,are highlighted as promising interventions for mitigating hypoxia-induced damage.Furthermore,we emphasize the potential of integrating in vitro,in vivo,and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.展开更多
Objective:To investigate the effects of Qishen Yiqi dropping pills serum on KATP channel opening and PI3K/AKT signaling pathway of hypoxic/reoxygenated H9C2 cardiocytes.Methods:H9C2 cardiocytes cultured in vitro were ...Objective:To investigate the effects of Qishen Yiqi dropping pills serum on KATP channel opening and PI3K/AKT signaling pathway of hypoxic/reoxygenated H9C2 cardiocytes.Methods:H9C2 cardiocytes cultured in vitro were randomly divided into five groups,A:H9C2 cell group B:H9C2 cells+H2O2 model group C:H9C2 cells+H2O2 model+Qishen Yiqi group D:H9C2 cells+H2O2 model+Qishen Yiqi+wort group E:H9C2 cells+H2O2 model+Qishenyiqi+5-HD group,the drug intervention is according to the corresponding conditions.CCK-8 method was used to detect the cell activity of each group;Western blot was used to detect the expression of AKT and P-Akt proteins in myocardial cells in each group.The current was recorded by the standard patch clamp whole cell recording method,and the current was collected and analyzed by Pclamp6.0 software.Results:CCK-8 test results showed that compared with group A,the activity of myocardial cells in group B was significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,the difference in group C was statistically significant(P<0.01);compared with C,cardiomyocyte activity in D and E group were significantly decreased,and the difference was statistically significant(P<0.05);WB results showed that compared with A,p-Akt protein expression in B,C,D and E groups were significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,p-Akt protein expression in C,D and E group were significantly increased,and the difference was statistically significant(P<0.01),but there was no significant difference in AKT expression among groups(P>0.05);The results of whole cell patch clamp experiment showed that the outward current of B was significantly increased compared with that of A,and the difference between groups was statistically significant(P<0.01);compared with group B,cardiomyocytes in group C further increased the outward current,and the difference between groups was statistically significant(P<0.01);compared with C,the current of D and E group were significantly decreased,with statistical significance between groups(P<0.01).Conclusion:QishenYiqi dropping pills can protect cardiomyocytes by activating p-Akt protein expression and KATP channel opening in H9C2 cardiomyocytes.展开更多
基金Regional Fund Project of National Natural Science Foundation of China(No.81460712)the Young and Middle-aged Teachers’Scientific Research Basic Ability Enhancement Project of Guangxi Universities(No.2020KY07026)Guangxi Graduate Education Innovation Program(No.YCXJ2021035)。
文摘In the state of acute myocardial ischemia,miRNA expression can regulate related genes and proteins,reduce myocardial cell damage,and thus play a protective role in the myocardium.However,the specific mechanism still needs to be further explored.Recent studies have found that the opening of the mitoKATP channel can regulate mitochondrial autophagy,and the initiation of miRNA-DNA methylation plays a regulatory role in inducing cell autophagy.The applicant research team previously found that Qishen Yiqi Dropping Pills could significantly improve myocardial ischemia by mediating MitokATP channels to regulate mitochondrial autophagy.,and animal experiments have confirmed that miR-155 plays a significant role in the aspect of autophagy regulates,inflammatory reaction and Vascular smooth muscle cell migration.Therefore,the applicant innovatively proposed that Qishen Yiqi Dropping Pills can regulate miRNA155-DNA methylation to mediate the opening of mitoKATP,thereby regulating mitochondrial autophagy and improving myocardial ischemia.In this paper,the association between mitochondrial autophagy and oxidative stress injury after myocardial ischemia was described,and the possible mechanism of Qisen Yiqi dropping pills regulating mitochondrial autophagy by regulating miRNA155-DNA methylation to mediate MitokATP to improve myocardial ischemia reperfusion injury was discussed,so as to provide theoretical ideas for related research.
基金supported by"Potential Medicinal Plants of Uzbekistan with Adaptogenic Effects and Their Molecular,Cellular,and Therapeutic Mechanisms"from the Innovative Development Agency under the Ministry of Higher Education,Science,and Innovation of the Republic of Uzbekistan(Grant No.FL-8323102109).
文摘Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases,including ischemia,heart failure,and hypertension.Under hypoxia,oxygen deficiency disrupts oxidative phosphorylation in mitochondria,impairing ATP production and generating reactive oxygen species(ROS).These reactive species induce mitochondrial dysfunction,leading to oxidative stress,calcium imbalance,and activation of apoptosis pathways.The mitochondrial ATP-sensitive potassium channel(mitoKATP)and mitochondrial permeability transition pore(mPTP)channels are particularly affected,contributing to membrane potential loss,cytochrome c release,and cell death.This review delves into the molecular mechanisms underlying hypoxia-induced cardiovascular diseases,with a focus on mitochondrial impairment,ion channel dysfunction,and ROS overproduction.Additionally,we examine hypoxia-inducible factor 1-alpha(HIF-1α)as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress.Antioxidants and compounds modulating key ion channels,such as mitoKATP and mPTP,are highlighted as promising interventions for mitigating hypoxia-induced damage.Furthermore,we emphasize the potential of integrating in vitro,in vivo,and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.
基金Regional Fund Project of National Natural Science Foundation of China(No.81460712)the Young and Middle-aged Teachers’Scientific Research Basic Ability Enhancement Project of Guangxi Universities(No.2020KY07026)Guangxi Graduate Education Innovation Program(No.YCXJ2021035)。
文摘Objective:To investigate the effects of Qishen Yiqi dropping pills serum on KATP channel opening and PI3K/AKT signaling pathway of hypoxic/reoxygenated H9C2 cardiocytes.Methods:H9C2 cardiocytes cultured in vitro were randomly divided into five groups,A:H9C2 cell group B:H9C2 cells+H2O2 model group C:H9C2 cells+H2O2 model+Qishen Yiqi group D:H9C2 cells+H2O2 model+Qishen Yiqi+wort group E:H9C2 cells+H2O2 model+Qishenyiqi+5-HD group,the drug intervention is according to the corresponding conditions.CCK-8 method was used to detect the cell activity of each group;Western blot was used to detect the expression of AKT and P-Akt proteins in myocardial cells in each group.The current was recorded by the standard patch clamp whole cell recording method,and the current was collected and analyzed by Pclamp6.0 software.Results:CCK-8 test results showed that compared with group A,the activity of myocardial cells in group B was significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,the difference in group C was statistically significant(P<0.01);compared with C,cardiomyocyte activity in D and E group were significantly decreased,and the difference was statistically significant(P<0.05);WB results showed that compared with A,p-Akt protein expression in B,C,D and E groups were significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,p-Akt protein expression in C,D and E group were significantly increased,and the difference was statistically significant(P<0.01),but there was no significant difference in AKT expression among groups(P>0.05);The results of whole cell patch clamp experiment showed that the outward current of B was significantly increased compared with that of A,and the difference between groups was statistically significant(P<0.01);compared with group B,cardiomyocytes in group C further increased the outward current,and the difference between groups was statistically significant(P<0.01);compared with C,the current of D and E group were significantly decreased,with statistical significance between groups(P<0.01).Conclusion:QishenYiqi dropping pills can protect cardiomyocytes by activating p-Akt protein expression and KATP channel opening in H9C2 cardiomyocytes.