血清氨基酸水平与间充质干细胞移植治疗心肌梗死疗效的相关性探讨

Correlation between serum amino acid level and the effect of mesenchymal stem cells transplantation therapy on myocardial infarction

目的探讨血清中氨基酸的含量变化和心脏功能的关系并用其评价间充质干细胞(MSC)移植治疗心肌梗死疗效。方法冠状动脉结扎制造大鼠心肌梗死模型,分为生理盐水对照组及20岁以下人MSC细胞治疗组,并于结扎同时分别在心肌梗死区域多点注射MSC细胞(1×107/只);1周后,用小动物超声仪检测射血分数(EF)、短轴缩短率(FS)等心功能指标。并于腹主动脉采血,取血清进行高效液相色谱质谱法测定甘氨酸等17种氨基酸含量。结果 1周后细胞移植组心功能均明显优于模型组(P<0.05)。模型组血清中17种氨基酸含量均明显高于正常组(P<0.05)。MSC移植组1周血清中16种氨基酸含量(除半胱氨酸外)明显低于模型组(P<0.05或P<0.01);但是半胱氨酸的含量明显高于模型组(P<0.05)。且发现组氨酸含量与模型组心功能指标呈显著负相关(P<0.05),半胱氨酸含量与细胞治疗组心功能指标呈显著负相关(P<0.05)。结论血清中氨基酸含量变化与MSC移植治疗心肌梗死疗效具有一定的相关性;支链氨基酸的显著性回落,提示MCS修复受损心肌侧重于增强内源性治疗的机会。但半胱氨酸的持续升高预示着氧化还原平衡状态的破坏需要长时间的恢复。17种氨基酸的特征性组合模式可能为MSC移植治疗心肌梗死疗效及机制提供新的思路。

Objective To investigate the relationship between serum level of amino acid and cardiac function and evaluate the therapy effects of mesenchymal stem cells（ MSC） transplantation. Methods Rat myocardial infarction（ MI） models obtained with coronary artery ligation were divided into the model control group（ treated with physiological saline）,periphery reinfusion treatment group of MSC from human at age 20 years old（ MSC therapy group）,MSC were injected multi-point in MI area（ 1 × 107/ rat）. One week later,ejection fraction（ EF）,fraction shortening（ FS） and other indicators of cardiac function were detected by a small animal ultrasound and the serum levels of 17 kinds of amino acids including glycine were examined. Results Heart function was significantly better in MSC therapy group compared with model control group（ P〈0. 05） after one week. Serum levels of 17 kinds of amino acids in model group were significantly higher than that in normal group（ P〈0. 05）.Except cysteine,the serum levels of 16 kinds of amino acids in MSC therapy group were significantly lower compared with the model control group after one week（ P〈0. 05 or P〈0. 01）,but cysteine content in MSC therapy group was significantly higher compared with the model control group（ P〈0. 05）. We also found that the histidine content was negatively correlated with heart function of the model control group（ P〈0. 05）. Cysteine content was negatively correlated with heart function of MSC therapy group（ P〈0. 05）. Conclusion The changes of serum amino acids content have some relevance with the efficacy of MSC transplantation on MI. Significantly lower level of branched chain amino acids suggests that the repair of MCS to damaged myocardium is focused on enhancing the treatment of endogenous. But the persistently elevated level of cysteine indicates that the damage of redox balance needs a long time to restore. The combination patterns of 17 kinds of amino acids may provide a new view for the efficacy and mechanism of MSC transplantation on MI.