| Objective:We improve preparation methods of taurine magnesium.Choose the best one from all the methods.We investigate the effects of TMCC on normal and abnormal sodium ion channel currents in rat ventricular cardiomyocytes suffered from hypoxia/reoxygenation.We evaluate the electrophysiogical effects of taurine magnesium to find out the mechanisms of antiarrhythmic effect and result in arrhythmic effect and result in arrhythmic effect..Methods:A series of experiments on the synthesis of taurine magnesium were carried out by the reproducibility experiment of literature method,acid environment reaction of magnesium oxide,Magnesium Sulfate synthesis and the synthesis of magnesium methanol.The experimental results show that magnesium methanol synthesis is the best one.Using magnesium methoxide and taurine as raw materials and stirring and refluxing under 100 oC for 1.5h,the obtained products obtained two hydrated taurine magnesium crystals by adding methanol and 8oC cold storage 48h crystallization technology.The effect of Langendorff's method on the acute isolation of single ventricular myocytes of rats was carried out by the method of retrograde aortic perfusion enzyme solution digestion.Under the voltage clamp mode,the whole cell patch clamp technique was adopted to record the effects of different concentrations of taurine on the ventricular myocytes of normal rats and the INaa of ventricular myocytes of hypoxia/reoxygenated rats.It is mainly divided into three concentrations:low(100 mol,L-1),medium(200 mol.L-1)and high(400 mol.L-1).Results:1.Part of the synthetic process:?1?reproducibility experiment of literature method.The product one IR map is close to the raw material magnesium hydroxide.The product ii IR was similar to taurine.The product three IR was similar to taurine.Product one melting point 384oC,unable to detect magnesium content;The second product is 311328oC and the magnesium content is 3.50%.The product was 314329oC and the magnesium content was 5.61%.?2?magnesium oxide acid environmental reaction method.The product IR was similar to taurine.The content of the product was 290297oCand the magnesium content was 1.37%.?3?magnesium sulfate synthesis.The product IR was similar to taurine,compared with the MgSO4 infrared spectrogram,without similar characteristic peaks.The product fusion process was292297oC,and the magnesium content was 2.89%.?4?magnesium methanol synthesis.The product one IR was similar to Mg?OH?2.The product two IR was similar to taurine.The product has a melting range of 297311oC,and the magnesium content is 4.62%.Product 2 melting point 300oC,magnesium content 7.78%.2.Effects of taurine magnesium on sodium channel in rat ventricular myocytesTMCC(100,200,400?mol·L-1)increased the INaa I-V curve and decreased the inward current.The current decreased at all test voltages,the most obvious reduction was about-45 mV.There is no parallel movement of the curve,which basically does not change the shape of the curve.TMCC(100,200,400?mol·L-1)inhibited INaa in a concentration dependent manner,and decreased 6.89%,12.84%and 17.49%at-45 mV depolarization voltage,respectively.TMCC(100,200,400?mol·L-1)inhibited the normal sodium current concentration and made the I-V curve move up,indicating that taurine magnesium had the function of blocking sodium channel,but this inhibition effect was weak.3.Effects of taurine magnesium on sodium channel in Rat Ventricular Myocytes Injured by anoxia/reoxygenation injuryThe results show that the peak value of INaa decreases,the I-V curve moves up and the TMCC(200,400?mol·L-1)can be restored to the INaa decrease due to the hypoxia/reoxygenation damage,and the I-V curve is moved down,and there is no parallel movement.It does not change the shape of the curve basically.It still maintains the original current pressure dependence,suggesting that TMCC has the same effect on INaa at different membrane potential levels.Amiodarone can partly restore the decrease of INaa caused by hypoxia/reoxygenation injury.The results of INaa kinetic study showed that hypoxia/reoxygenation caused the activation curve to move right,the activation slowed down,the inactivation curve left,the inactivation accelerated,and the TMCC(200,400?mol·L-1)and 24.24 mol.L-1amiodarone could restore the left inactivation curve and slow the inactivation,but there was no significant difference in the effect on the activation.Conclusion:Method 1 showed that there existed some defects and shortcomings,and the experiment is still needed to be further discussed.The results of Method 2 and Method 3 indicated that many problems such as inadequate reaction of raw materials and a large number of impurities which were difficult to separate existed.The results showed that Method 4 was the best one.The reaction conditions were stirred and heated under 1000C,and the reaction time was 1.5h.The conditions of crystallization were:in methanol,48 hours placed under 8oC.The effect of taurine magnesium(100,200,400?mol·L-1)synthesized by the optimum synthesis method on the sodium ion channel of rat ventricular myocytes was carried out.The results showed that taurine magnesium had a concentration dependent inhibition on the normal sodium current,and the I-V curve moved up.It indicated that taurine magnesium had the effect of blocking sodium channel.Taurine magnesium had a weak inhibitory effect on sodium channel,indicating that taurine magnesium is a kind of mild compound on sodium channel.Anoxia/reoxygenation reduced the peak value of INaa and shifted the I-V curve.This model was successfully prepared.TMCC decreased the sodium current caused by the concentration dependent recovery of hypoxia/reoxygenation injury in the inactivation process of the sodium channel,causing the I-V curve to move down,and the action of amiodarone was between 100200?mol·L-1TMCC.TMCC not only has a certain effect on the normal cardiac myocyte INa,but also can make the cell INa in the pathological state regain the ion balance point,which is beneficial to the treatment of arrhythmia and reduce the risk of arrhythmia. |
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