The effects of l-, d- and dl-propranolol on antipyrine metabolism and isoprenaline-induced tachycardia were studied in rabbits. The plasma concentration of antipyrine was assayed by Brodie’s spectrophotometric method...The effects of l-, d- and dl-propranolol on antipyrine metabolism and isoprenaline-induced tachycardia were studied in rabbits. The plasma concentration of antipyrine was assayed by Brodie’s spectrophotometric method and the change of heart rate was evaluated by ECG. Both isomers of propranolol hydrochloride were administered iv （800 μg/kg） to the rabbits. d-propranolol produced an antipyrine t 1/2 of 2.67±0.77h and a cl of 0.49±0.1 l/h while its levo-form produced an antipyrine t 1/2 of 1.7±0.39h and a cl of 0.88±0.22 l/h. The differences between the half-lives and between the clearances were statistically significant （P【0.05 for t 1/2, P【0.01 for cl）. The inhibitory effects of l- and d-propranolol on isoprenaline-induced tachycardia were assessed. l-propranolol yielded an ID<sub>50</sub> which was only 1/88 of d-propranolol’s. Our studies showed that the β-receptor blocking activity of propranolol mainly came. from its levoform while the effect on antipyrine metabolism came from its dextro-form.展开更多
Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs(miRNAs) play multiple roles in biological processes...Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs(miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34 c-5 p on cardiac hypertrophy and the mechanism involved. The expression of miR-34 c-5 p was proved to be elevated in heart tissues from isoprenaline(ISO)-infused mice. ISO also promoted miR-34 c-5 p level in primary cultures of neonatal rat cardiomyocytes(NRCMs). Transfection with miR-34 c-5 p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor(Anf) and β-myosin heavy chain(β-Mhc) in NRCMs. In contrast, treatment with miR-34 c-5 p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34 c-5 p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34 c-5 p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34 c-5 p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4 B(ATG4 B) was identified as a direct target of miR-34 c-5 p, and miR-34 c-5 p was certified to interact with 3’untranslated region of Atg4 b mRNA by dual-luciferase reporter assay. miR-34 c-5 p reduced the expression of ATG4 B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34 c-5 p abolished the detrimental effects of ISO by restoring ATG4 B and increasing autophagy. In conclusion, our findings illuminate that miR-34 c-5 p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4 B and autophagy. It suggests that regulation of miR-34 c-5 p may offer a new way for handling hypertrophy-related cardiac dysfunction.展开更多
β-Cyclodextrin phosphate (β-CD-phosphate) was used as a selector for separating chiral drugs by capillary electrophoresis (CE). A solution comprising of 120 mmol/L Britton Robinson buffer (BRB) containing 10 mmol/L ...β-Cyclodextrin phosphate (β-CD-phosphate) was used as a selector for separating chiral drugs by capillary electrophoresis (CE). A solution comprising of 120 mmol/L Britton Robinson buffer (BRB) containing 10 mmol/L 0-CD phosphate with the pH adjusted to 7.0 was used as the background electrolyte (BGE), and a small amount of analyte was injected (600v/1s). Triethylamine, diethylamine, triethanolamine, diethanolamine, Tris added as modifier were compared. Isoprenaline, methoxamine, oxprenolol, practolol were successfully resolved.展开更多
Background: Tako-tsubo cardiomyopathy occurs typicallly after an intrinsic adrenergic hyperstimulation triggered by a psychological or physically stressful event. Exceptionally, it may be caused by an exogenous hypera...Background: Tako-tsubo cardiomyopathy occurs typicallly after an intrinsic adrenergic hyperstimulation triggered by a psychological or physically stressful event. Exceptionally, it may be caused by an exogenous hyperadrenergism. We report the case of an 85 year old man, hypertensive, with a history of ischemic stroke. He consulted for signs of heart failure with recurrent dizziness two weeks which was explained by an atrioventricular block. Initial echocardiography showed left ventricular ejection fraction to 60% with no wall motion abnormalities. The patient received iso-prenaline (0.02 mcg/kg/mn) for 20 hours before the implantation of a single chamber pacemaker. At 24 hours of admission an acute pulmonary edema occurred. The control echocardiography showed impaired left ventricular ejection fraction of 25% with apical ballooning and akinesis was also found on ventricu-lography. Coronary angiography showed no significant coronary lesions. Troponin level was elevated to 2 ng/ml. The pulmonary edema was then controlled. Subsequent clinical and echocardiographic were favo- rable after two weeks which was consistent with the diagnosis of tako-tsubo cardiomyopathy. Conclusion: This case illustrates an example of tako-tsubo syndrome induced by an exogenous catecholergic stimulation (isoprenaline) combined with an endogenous release after a pacemaker implantation which confirmed the physiopathological hypothesis of a catecholamine-mediated stunning in tako-tsubo cardiomyopathy.展开更多
Background:To study the protective effect of different medicinal parts of honeysuckle on myocardial ischemia injury in rats.Method:SD mice were randomly divided into 6 groups:the normal group,model group,compound salv...Background:To study the protective effect of different medicinal parts of honeysuckle on myocardial ischemia injury in rats.Method:SD mice were randomly divided into 6 groups:the normal group,model group,compound salvia miltiorrhiza group,Lonicera japonica Thunb.of flower bud group,flower group,and the stem leaf group.There were 8 rats in each group,including 4 males and 4 females.The normal group and model group were given equal amount of distilled water,whereas the other dosage groups were given the appropriate drug by intragastric administration,continuous gavage for 14 days.From the 12 days,in addition to the normal group were injected of the same amount of normal saline,the other groups were injected with 5g/kg.Injection of isoproterenol to establish the mouce mycardial ischemia model,its continuously 3d.To detect the serum of AST,CK,CK-MB,LDH and the myocardial issue of Chinese super oxideismutase and malondialdehyde level.Results:Compared with normal group,the levels of AST,CK,CK-MB,cTn-I,LDH and malondialdehyde were significantly increased in the model group(P<0.01)and the level of super oxideismutase decreased significantly(P<0.01)the levels of AST,CK,CK-MB,cTn-I,LDH and malondialdehyde in the serum of flower bud group,flower group and stem leaf group were significantly decreased(P<0.05),and the decreasing level of flower bud group,flower,leaf group of AST,CK,CK-MB,cTn-I,LDH and malondialdehyde was flower bud group>flower>leaf group,the activity of super oxideismutase was obviously increased,and the activity level of super oxideismutase of flower bud group,flower group and stem leaf group was flower bud group>flower>leaf group.Conclusion:In the myocardial ischemic injury model of rats induced by isoproterenol,Lonicera japonica Thunb.had a protective effect in all parts,and Lonicera japonica Thunb.bud had the greatest protective effect.展开更多
文摘The effects of l-, d- and dl-propranolol on antipyrine metabolism and isoprenaline-induced tachycardia were studied in rabbits. The plasma concentration of antipyrine was assayed by Brodie’s spectrophotometric method and the change of heart rate was evaluated by ECG. Both isomers of propranolol hydrochloride were administered iv （800 μg/kg） to the rabbits. d-propranolol produced an antipyrine t 1/2 of 2.67±0.77h and a cl of 0.49±0.1 l/h while its levo-form produced an antipyrine t 1/2 of 1.7±0.39h and a cl of 0.88±0.22 l/h. The differences between the half-lives and between the clearances were statistically significant （P【0.05 for t 1/2, P【0.01 for cl）. The inhibitory effects of l- and d-propranolol on isoprenaline-induced tachycardia were assessed. l-propranolol yielded an ID<sub>50</sub> which was only 1/88 of d-propranolol’s. Our studies showed that the β-receptor blocking activity of propranolol mainly came. from its levoform while the effect on antipyrine metabolism came from its dextro-form.
基金supported by grants from the National Natural Science Foundation of China (81872860,81673433,and82070268)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01Y093,China)+4 种基金National Major Special Projects for the Creation and Manufacture of New Drugs (2019ZX09301104,China)National Engineering and Technology Research Center for New drug Druggability Evaluation (Seed Program of Guangdong Province,2017B090903004,China)Special Program for Applied Science and Technology of Guangdong Province (2015B020232009,China)Guangdong Basic and Applied Basic Research Foundation(2020A1515011512,China)Young Teacher Training Program of Sun Yat-sen University (18ykpy26,China)。
文摘Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs(miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34 c-5 p on cardiac hypertrophy and the mechanism involved. The expression of miR-34 c-5 p was proved to be elevated in heart tissues from isoprenaline(ISO)-infused mice. ISO also promoted miR-34 c-5 p level in primary cultures of neonatal rat cardiomyocytes(NRCMs). Transfection with miR-34 c-5 p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor(Anf) and β-myosin heavy chain(β-Mhc) in NRCMs. In contrast, treatment with miR-34 c-5 p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34 c-5 p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34 c-5 p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34 c-5 p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4 B(ATG4 B) was identified as a direct target of miR-34 c-5 p, and miR-34 c-5 p was certified to interact with 3’untranslated region of Atg4 b mRNA by dual-luciferase reporter assay. miR-34 c-5 p reduced the expression of ATG4 B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34 c-5 p abolished the detrimental effects of ISO by restoring ATG4 B and increasing autophagy. In conclusion, our findings illuminate that miR-34 c-5 p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4 B and autophagy. It suggests that regulation of miR-34 c-5 p may offer a new way for handling hypertrophy-related cardiac dysfunction.
文摘β-Cyclodextrin phosphate (β-CD-phosphate) was used as a selector for separating chiral drugs by capillary electrophoresis (CE). A solution comprising of 120 mmol/L Britton Robinson buffer (BRB) containing 10 mmol/L 0-CD phosphate with the pH adjusted to 7.0 was used as the background electrolyte (BGE), and a small amount of analyte was injected (600v/1s). Triethylamine, diethylamine, triethanolamine, diethanolamine, Tris added as modifier were compared. Isoprenaline, methoxamine, oxprenolol, practolol were successfully resolved.
文摘Background: Tako-tsubo cardiomyopathy occurs typicallly after an intrinsic adrenergic hyperstimulation triggered by a psychological or physically stressful event. Exceptionally, it may be caused by an exogenous hyperadrenergism. We report the case of an 85 year old man, hypertensive, with a history of ischemic stroke. He consulted for signs of heart failure with recurrent dizziness two weeks which was explained by an atrioventricular block. Initial echocardiography showed left ventricular ejection fraction to 60% with no wall motion abnormalities. The patient received iso-prenaline (0.02 mcg/kg/mn) for 20 hours before the implantation of a single chamber pacemaker. At 24 hours of admission an acute pulmonary edema occurred. The control echocardiography showed impaired left ventricular ejection fraction of 25% with apical ballooning and akinesis was also found on ventricu-lography. Coronary angiography showed no significant coronary lesions. Troponin level was elevated to 2 ng/ml. The pulmonary edema was then controlled. Subsequent clinical and echocardiographic were favo- rable after two weeks which was consistent with the diagnosis of tako-tsubo cardiomyopathy. Conclusion: This case illustrates an example of tako-tsubo syndrome induced by an exogenous catecholergic stimulation (isoprenaline) combined with an endogenous release after a pacemaker implantation which confirmed the physiopathological hypothesis of a catecholamine-mediated stunning in tako-tsubo cardiomyopathy.
基金This study was supported by 2016 National College Students Innovation and Entrepreneurship Training Project(201610599001)Guangxi Key R&D Project(Gui Ke AB18221095)Youjiang Medical College for Nationalities High-level Talent Research Project(01002018079).
文摘Background:To study the protective effect of different medicinal parts of honeysuckle on myocardial ischemia injury in rats.Method:SD mice were randomly divided into 6 groups:the normal group,model group,compound salvia miltiorrhiza group,Lonicera japonica Thunb.of flower bud group,flower group,and the stem leaf group.There were 8 rats in each group,including 4 males and 4 females.The normal group and model group were given equal amount of distilled water,whereas the other dosage groups were given the appropriate drug by intragastric administration,continuous gavage for 14 days.From the 12 days,in addition to the normal group were injected of the same amount of normal saline,the other groups were injected with 5g/kg.Injection of isoproterenol to establish the mouce mycardial ischemia model,its continuously 3d.To detect the serum of AST,CK,CK-MB,LDH and the myocardial issue of Chinese super oxideismutase and malondialdehyde level.Results:Compared with normal group,the levels of AST,CK,CK-MB,cTn-I,LDH and malondialdehyde were significantly increased in the model group(P<0.01)and the level of super oxideismutase decreased significantly(P<0.01)the levels of AST,CK,CK-MB,cTn-I,LDH and malondialdehyde in the serum of flower bud group,flower group and stem leaf group were significantly decreased(P<0.05),and the decreasing level of flower bud group,flower,leaf group of AST,CK,CK-MB,cTn-I,LDH and malondialdehyde was flower bud group>flower>leaf group,the activity of super oxideismutase was obviously increased,and the activity level of super oxideismutase of flower bud group,flower group and stem leaf group was flower bud group>flower>leaf group.Conclusion:In the myocardial ischemic injury model of rats induced by isoproterenol,Lonicera japonica Thunb.had a protective effect in all parts,and Lonicera japonica Thunb.bud had the greatest protective effect.
