This study aimed to examine the functional role of micro RNA-20（miR-20） and its potential target, Kir6.1, in ischemic myocardiocytes. The expression of miR-20 was detected by real-time PCR. Myocardiocytes were stain...This study aimed to examine the functional role of micro RNA-20（miR-20） and its potential target, Kir6.1, in ischemic myocardiocytes. The expression of miR-20 was detected by real-time PCR. Myocardiocytes were stained with terminal deoxynucleotidyl transferase d UTP nick end labeling（TUNEL） reagent for apoptosis evaluation. Western blotting was used to detect the Kir6.1 protein in ischemic myocardiocytes transfected with miR-20 mimics or inhibitors. Luciferase reporter gene assay was performed to confirm the targeting effect of miR-20 on KCNJ8. The results showed that miR-20 was remarkably down-regulated, while the KATP subunit Kir6.1 was significantly up-regulated, during myocardial ischemia. The miR-20 overexpression promoted the apoptosis of ischemic myocardiocytes, but showed no such effect on normal cells. Under ischemic condition, myocardiocytes transfected with miR-20 mimics expressed less Kir6.1. On the contrary, inhibiting miR-20 increased the expression of Kir6.1 in the cells. Co-transfection of miR-20 mimics with the KCNJ8 3＇-UTR plasmid into HEK293 cells consistently produced less luciferase activity than transfection of the plasmid alone. It was concluded that miR-20 may regulate myocardiac ischemia by targeting KATP subunit Kir6.1 to accelerate the cell apoptosis. Therefore miR-20 may serve as a therapeutic target for myocardial ischemic disease.展开更多
Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic b...Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding(AAB).The effects of natakalim(1,3,9 mg·kg-1·d-1,10 weeks)were assessed on myocardial hypertrophy and heart failure,cardiac histology,vasoactive compounds,and gene expression.Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels.Results Ten weeks after the onset of pressure overload,natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure.Natakalim inhibited the changes of left ventricular haemodynamic parameters,reversed the increase of heart mass index,left ventricular weight index and lung weight index remarkably.Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim.Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats.The content of serum NO and plasma PGI2 was increased,while that of plasma ET-1 and cardiac tissue hydroxyproline,ANP and BNP mRNA was down-regulated in natakalim-treated rats.Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats;however,natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE.Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.展开更多
Objective:To study the effect of combination of acupuncture and medicine on the expression of ATP sensitive potassium channel related proteins Kir6.1 and Kir6.2 in rats with myocardial infarction,and to study the poss...Objective:To study the effect of combination of acupuncture and medicine on the expression of ATP sensitive potassium channel related proteins Kir6.1 and Kir6.2 in rats with myocardial infarction,and to study the possible mechanism of combination of acupuncture and medicine on the improvement of myocardial infarction,so as to provide experimental data basis for the development of new treatment methods for myocardial infarction.Methods:65 healthy male SD rats were randomly selected as the control group.The other rats were fed with high-fat food for three weeks.The rats in the control group were injected with normal saline subcutaneously,and the other rats were injected with isoproterenol hydrochloride in the same way.Through ECG comparison,40 successful Mi rats were randomly divided into model group,acupuncture group,western medicine group and acupuncture drug combination group,with 10 rats in each group.After the corresponding treatment,the ECG changes of rats in each group were observed,the pathological changes of rat cardiomyocytes were observed by HE staining,and the expression of ATP sensitive potassium channel(Kir6.1,Kir6.2)protein was detected by Western blot.Results:compared with the control group,40 experimental specimens in the experimental group showed significant changes in cardiomyocyte protein The expression of Kir6.1 and Kir6.2 increased,and the difference was statistically significant.After treatment,compared with the model group,the protein expression of Kir6.1 and Kir6.2 in cardiomyocytes of Western medicine group,acupuncture group and acupuncture drug combination group showed a downward trend,among which the decline degree of acupuncture drug combination group was the most obvious,and the difference was statistically significant.The decline degree of acupuncture group and Western medicine group was not significant,and there was no significant difference Conclusion:acupuncture combined with medicine has a significant effect on improving myocardial infarction in rats,which may be related to the expression of ATP sensitive potassium channel related proteins Kir6.1 and Kir6.2 in rat cardiomyocytes.展开更多
OBJECTIVE: To observe the impact of total flavonoids from Ganshanbian(Herba Hyperici Attenuati)on the expression of vascular smooth muscle membrane L-type calcium channel alpha1 C subunit(CaL-α1C) and ATP-sensitive K...OBJECTIVE: To observe the impact of total flavonoids from Ganshanbian(Herba Hyperici Attenuati)on the expression of vascular smooth muscle membrane L-type calcium channel alpha1 C subunit(CaL-α1C) and ATP-sensitive K+channel(KATP)-Kir6.1mRNA, and explore the mechanisms of the antiarrhythmic effect of Ganshanbian(Herba Hyperici Attenuati)total flavonoids.METHODS: The treatment group was fed total flavonoids from Ganshanbian(Herba Hyperici Attenuati)for 7 days by gavage with 100 mg·kg﹣1·d﹣1.The blank control group and model control group were given the same amount of normal saline for 7 d.Arrhythmias were induced by performing a myocardial ischemia-reperfusion and electrocardiogram was observed. Reverse transcription-polymerase chain reaction was used to detect the expression of CaL-α1CandKATP-Kir6.1 mRNA in the myocardial cell membrane of all groups of rats. RESULTS: Total flavonoids from Ganshanbian(Herba Hyperici Attenuati) can delay the appearance of myocardial ischemia reperfusion arrhythmias,shorten the duration of myocardial ischemia reperfusion arrhythmias, reduce heart rate, reduce cell membrane expression of CaL-α1C mRNA and enhance the expression of KATP-Kir6.1 mRNAin myocardial ischemia-reperfusion arrhythmic rats.CONCLUSION: Total flavonoids from Ganshanbian(Herba Hyperici Attenuati) can alleviate arrhythmias by affecting the expression of L-type calcium channels and ATP-sensitiveK+ channels.展开更多
基金supported by the National Natural Science Foundation of China(No.30700262)
文摘This study aimed to examine the functional role of micro RNA-20（miR-20） and its potential target, Kir6.1, in ischemic myocardiocytes. The expression of miR-20 was detected by real-time PCR. Myocardiocytes were stained with terminal deoxynucleotidyl transferase d UTP nick end labeling（TUNEL） reagent for apoptosis evaluation. Western blotting was used to detect the Kir6.1 protein in ischemic myocardiocytes transfected with miR-20 mimics or inhibitors. Luciferase reporter gene assay was performed to confirm the targeting effect of miR-20 on KCNJ8. The results showed that miR-20 was remarkably down-regulated, while the KATP subunit Kir6.1 was significantly up-regulated, during myocardial ischemia. The miR-20 overexpression promoted the apoptosis of ischemic myocardiocytes, but showed no such effect on normal cells. Under ischemic condition, myocardiocytes transfected with miR-20 mimics expressed less Kir6.1. On the contrary, inhibiting miR-20 increased the expression of Kir6.1 in the cells. Co-transfection of miR-20 mimics with the KCNJ8 3＇-UTR plasmid into HEK293 cells consistently produced less luciferase activity than transfection of the plasmid alone. It was concluded that miR-20 may regulate myocardiac ischemia by targeting KATP subunit Kir6.1 to accelerate the cell apoptosis. Therefore miR-20 may serve as a therapeutic target for myocardial ischemic disease.
文摘Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding(AAB).The effects of natakalim(1,3,9 mg·kg-1·d-1,10 weeks)were assessed on myocardial hypertrophy and heart failure,cardiac histology,vasoactive compounds,and gene expression.Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels.Results Ten weeks after the onset of pressure overload,natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure.Natakalim inhibited the changes of left ventricular haemodynamic parameters,reversed the increase of heart mass index,left ventricular weight index and lung weight index remarkably.Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim.Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats.The content of serum NO and plasma PGI2 was increased,while that of plasma ET-1 and cardiac tissue hydroxyproline,ANP and BNP mRNA was down-regulated in natakalim-treated rats.Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats;however,natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE.Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.
基金Key Project of Liaoning Provincial Science and Technology Foundation(No.20180530079)。
文摘Objective:To study the effect of combination of acupuncture and medicine on the expression of ATP sensitive potassium channel related proteins Kir6.1 and Kir6.2 in rats with myocardial infarction,and to study the possible mechanism of combination of acupuncture and medicine on the improvement of myocardial infarction,so as to provide experimental data basis for the development of new treatment methods for myocardial infarction.Methods:65 healthy male SD rats were randomly selected as the control group.The other rats were fed with high-fat food for three weeks.The rats in the control group were injected with normal saline subcutaneously,and the other rats were injected with isoproterenol hydrochloride in the same way.Through ECG comparison,40 successful Mi rats were randomly divided into model group,acupuncture group,western medicine group and acupuncture drug combination group,with 10 rats in each group.After the corresponding treatment,the ECG changes of rats in each group were observed,the pathological changes of rat cardiomyocytes were observed by HE staining,and the expression of ATP sensitive potassium channel(Kir6.1,Kir6.2)protein was detected by Western blot.Results:compared with the control group,40 experimental specimens in the experimental group showed significant changes in cardiomyocyte protein The expression of Kir6.1 and Kir6.2 increased,and the difference was statistically significant.After treatment,compared with the model group,the protein expression of Kir6.1 and Kir6.2 in cardiomyocytes of Western medicine group,acupuncture group and acupuncture drug combination group showed a downward trend,among which the decline degree of acupuncture drug combination group was the most obvious,and the difference was statistically significant.The decline degree of acupuncture group and Western medicine group was not significant,and there was no significant difference Conclusion:acupuncture combined with medicine has a significant effect on improving myocardial infarction in rats,which may be related to the expression of ATP sensitive potassium channel related proteins Kir6.1 and Kir6.2 in rat cardiomyocytes.
基金Supported by National Natural Science Foundation of China(Proteomics research on the complexes of Ganshanbian(Herba Hyperici Attenuati)and Salvia miltiorrhiza anti-reperfusion arrhythmia based on the iTRAQ technology.No.81173185)Key Project of Natural Science Foundation of Heilongjiang Province(Proteomics research on the complexes of Ganshanbian(Herba Hyperici Attenuati)and Salvia miltiorrhiza anti-reperfusion arrhythmia based on the iTRAQ technology.No.ZD201111)+1 种基金Heilongjiang Province Graduate Students Research Key Project(Proteomics research on the complexes of Ganshanbian(Herba Hyperici Attenuati)and Salvia miltiorrhiza anti-reperfusion arrhythmia based on the iTRAQ technology.No.YJSCX2012-334HLJ)Outstanding Talents Support Program of Heilongjiang University of Chinese Medicine(Proteomics research on the complexes of Ganshanbian(Herba Hyperici Attenuati)and Salvia miltiorrhiza anti-reperfusion arrhythmia based on the iTRAQ technology,2012)
文摘OBJECTIVE: To observe the impact of total flavonoids from Ganshanbian(Herba Hyperici Attenuati)on the expression of vascular smooth muscle membrane L-type calcium channel alpha1 C subunit(CaL-α1C) and ATP-sensitive K+channel(KATP)-Kir6.1mRNA, and explore the mechanisms of the antiarrhythmic effect of Ganshanbian(Herba Hyperici Attenuati)total flavonoids.METHODS: The treatment group was fed total flavonoids from Ganshanbian(Herba Hyperici Attenuati)for 7 days by gavage with 100 mg·kg﹣1·d﹣1.The blank control group and model control group were given the same amount of normal saline for 7 d.Arrhythmias were induced by performing a myocardial ischemia-reperfusion and electrocardiogram was observed. Reverse transcription-polymerase chain reaction was used to detect the expression of CaL-α1CandKATP-Kir6.1 mRNA in the myocardial cell membrane of all groups of rats. RESULTS: Total flavonoids from Ganshanbian(Herba Hyperici Attenuati) can delay the appearance of myocardial ischemia reperfusion arrhythmias,shorten the duration of myocardial ischemia reperfusion arrhythmias, reduce heart rate, reduce cell membrane expression of CaL-α1C mRNA and enhance the expression of KATP-Kir6.1 mRNAin myocardial ischemia-reperfusion arrhythmic rats.CONCLUSION: Total flavonoids from Ganshanbian(Herba Hyperici Attenuati) can alleviate arrhythmias by affecting the expression of L-type calcium channels and ATP-sensitiveK+ channels.
基金supported by the Science Research Foundation of Ministry of Health of China-Pharmaceutical and Health Care Science and Technology Major Program of Zhejiang Province,China(No.WKJ2009-2-030)Traditional Chinese Medicine Key Discipline Construction Project of Zhejiang Province,China(No.2012-XK-A28)
基金supported by National Heart, Lung, and Blood Institute Grant (No. HL-067890)National Institutes of Health Grant (No. HD060959)the American Heart Association (No. 09GRNT2010037)
