The role and molecular mechanisms of long noncoding RNAs in cardiac diseases / 药学学报

Long noncoding RNAs (lncRNAs) are a class of RNAs that are more than 200 nucleotides in length with no protein coding property. LncRNAs are involved in almost every cellular process through multiple mechanisms. LncRNAs can directly bind to molecules in cells such as proteins, RNA, and DNA, to regulate cellular functions by influencing processes including transcription, translation, and molecular transporting. Recent researches showed lncRNAs are key regulators of serious cardiac diseases, especially in development and progression of cardiac ischemia, arrhythmia, cardiac fibrosis, and heart failure. This article mainly summarizes the function and mechanism of lncRNAs in cardiac diseases and gives reasonable prospect of lncRNAs in the future.

Effects of matrine, oxymatrine and resveratrol on HERG channel expression / 药学学报

Because HERG potassium channel has important effects on both proarrhythmia and antiarrhythmia, we use immunofluorescence and Western blotting methods to detect the expression of HERG channel of HERG-HEK cells in different concentrations of matrine, oxymatrine and resveratrol. The findings showed that both matrine (1 micromol x L(-1) ) and oxymatrine ( 1micromol x L (-1) ) increased HERG channel expression ( n = 5, P < 0. 05 ) , while matrine (100 micromol x L(-1) ) decreased HERG channel expression ( n = 5, P < 0. 05), resveratrol didn't affect HERG channel expression. In conclusion, different concentrations of matrine and oxymatrine affect HERG channel expression, while there is no relationship between resveratrol and HERG channel expression. It provides a theoretical support for the safety and mechanism of anti-arrhythmic drugs.

The cardioprotective effect and mechanism of lumbrokinase / 药学学报

<p><b>AIM</b>To investigate the protective effect of lumbrokinase against myocardial ischemia and to further explore its underlying mechanisms.</p><p><b>METHODS</b>The effect of lumbrokinase on myocardial ischemia was observed by a model of acute myocardial infarction due to permanent ligation of the left anterior descending coronary artery in rats. Patch-clamp technique and laser scanning confocal microscopy were utilized to study the action of lumbrokinase on L-type calcium current (ICa-L) and intracellular calcium concentration ([Ca2+]i).</p><p><b>RESULTS</b>Lumbrokinase decreased the infarct size of myocardium in a dose-dependent manner. The inhibitory rate of lumbrokinase at the dose of 20, 40 and 80 mg x kg(-1) was 7.7%, 34.6% and 46.2%, respectively. The electrophysiological studies displayed that, at + 10 mV, the ICa-L was markedly reduced from (-14.42 +/- 1.53) pA/pF to (-11.33 +/- 1.40) pA/pF (decreased by 21.4%, P <0.01) and (-9.92 +/- 1.31) pA/pF (decreased by 36.5%, P <0.01) by lumbrokinase (10 and 50 micromol x L(-1)), respectively. Confocal experiments showed that 10 micromol x L(-1) lumbrokinase showed no obvious effects on [Ca2+]i at resting states (P > 0.05). However, the increase of [Ca2+]i induced by 60 mmol x L(-1) KCl was distinctly limited by 10 micromol x L(-1) lumbrokinase (P <0.01). Within 240 s, the no obvious peak value of fluorescent intensity (FI) was shown.</p><p><b>CONCLUSION</b>Lumbrokinase showed protective action against myocardial infarction in rats. The possible mechanisms of anti-ischemia could be attributed to decreasing ICa-L and [Ca2+] of ventricular myocytes in rats.</p>

Integration between M3 muscarinic acetylcholine receptor and connexin 43 as antiarrhythmic targets in rat ventricular myocardium / 药学学报

<p><b>AIM</b>To optimize the method of investigating structural integration between proteins and study the integration between arrhythmia related proteins in molecular level.</p><p><b>METHODS</b>Immunostaining the normal ventricular myocytes was used to observe the distribution of connexin 43 and muscarinic acetylcholine receptor (mAChR). The five mAChR subtypes were precipitated using immunoprecipitation. Then, SDS-PAGE and Western blotting with the anti-connexin 43 antibody were performed to observe whether they were structurally integrated. Further, different concentrations of detergent were used to observe whether this relationship could be broken.</p><p><b>RESULTS</b>The five subtypes of mAChR existed in the cardiac myocyte of the rat, and all the five mAChR subtypes combined with connexin 43. In the normal rat ventricular myocyte membrane, connexin 43 and M3 receptor are co-located. When adding certain concentration of detergent to the membrane protein, the integration between M3 receptor and connexin 43 was broken, and the phosphorylated form of connexin 43 integrated with M3 receptor.</p><p><b>CONCLUSION</b>The results indicated that the structural integration between mAChR and phosphorylation of connexin 43 existed in rat ventricular myocardium, and this integration could be broken by certain concentration of detergent.</p>

Establishment of a novel arrhythmia model in rats / 药学学报

<p><b>AIM</b>To establish a novel arrhythmia model in rats.</p><p><b>METHODS</b>Coronary artery occlusion was produced in hyperlipidemic rats after the animals were fed a high fat and cholesterol chow for 15 days. The incidence, duration and score of arrhythmias were determined 1 hour after coronary occlusion.</p><p><b>RESULTS</b>The incidence, duration and score of arrhythmia induced by coronary artery occlusion increased significantly in hyperlipidemic rats compared with those in normal rats (P < 0.05). In normal rats, pretreatment with amiodarone 60 mg x kg(-1) or verapamil 25 mg x kg(-1) 3 days before coronary artery occlusion did not influence the incidence, duration and score of arrhythmia (P > 0.05). In hyperlipidemic rats, amiodarone 60 mg x kg(-1) decreased the incidence, duration and score of arrhythmia (P < 0.05), but not verapamil 25 mg x kg(-1) (P > 0.05).</p><p><b>CONCLUSION</b>The novel arrhythmia model induced by coronary artery occlusion in hyperlipidemic rats is reliable and similar to the pathophysiological state in human being.</p>

Dihydromyricetin exerted its vasoconstrictive effects by increasing intracellular Ca~(2+) in isolated canine carotid artery / 中国药理学通报

Aim To investigate the effect of dihydromyricetin on canine carotid artery and the underlying mechanism.Methods The in vitro isometric tension measurement technique was employed to investigate the effect of dihydromyricetin on canine carotid artery rings.Laser scanning confocal microscope technique was used to measure the dynamic change of intracellular calcium concentration in single VSMC.Results Dihydromyricetin(1～300 ?mol?L-1)caused a concentration-dependent contraction of both endothelium-intact and endothelium-denuded rings.This constrictive effect was attenuated in Ca2+-free solution(P

Dihydromyricetin induce apoptosis in AGZY-83-a tumor cells / 中国药理学通报

Aim To investigate the effects of dihydromyricetin on the apoptosis in AGZY-83-a tumor cells and its relevant mechanisms.Methods The survival rate of AGZY-83-a cells was assayed by MTT dye reduction.The cellular apoptosis was analyzed by TUNEL method and caspase-3 activity.The intracellular free calcium i was detected to explore the apoptotic mechanism of dihydromyricetin.Results In the MTT assay,dihydromyricetin 50?mol?L-1 significantly inhibited survival ratios of AGZY-83-a cells at dose-and time-dependent manner.It was demonstrated in TUNEL assay that dihydromyricetin could induce the apoptosis of AGZY-83-a cells in a concentration-dependent manner.The examination of Caspase-3 activity indicated that the dihydromyricetin could induce the apoptosis of AGZY-83-a cells,which was dose-dependent activation of Caspase-3 in AGZY-83-a cells.The detection of the intracellular i showed that the average FI of the i could be markedly increased to 20-fold as the basic condition.Conclusions Dihydromyricetin can induce the apoptosis in AGZY-83-a cells,which is associated with the overload of the intracellular i.