外源性硫化氢预处理骨髓间充质干细胞移植治疗大鼠心肌梗死

摘要

BACKGROUND:Bone marrow mesenchymal stem cells (BMSCs) transplantation can promote cardiac repair after myocardial infarction, but it has been limited by the low cellsurvival rate. OBJECTIVE:To study the effect of hydrogen sulfide (H 2 S) on the BMSCs transplantation for treatment of myocardial infarction. METHODS:BMSCs were separated and cultivated form Sprague-Dawley rats weighing (100±20) g. The 4th generation cells were used for later experiment, and marked by DAPI at 2 hours before use. Fifty male Sprague-Dawley rats, weighing (200±20) g had been divided into five groups:Sham group (n=10) and four transplantation groups:BMSCs (n=10), H 2 S-BMSCs (n=10), H 2 S (n=10), normal saline (n=10). The myocardial infarction model of four groups was established except of sham group (only thread without ligation). The cardiac function was measured by echocardiogram at 4 weeks after celltransplantation. The col agen in the infarction area was tested by Masson staining. RESULTS AND CONCLUSION:Severe myocardial fibrosis was found in the normal saline group, with no myocardial regeneration in the infarct area. H 2 S-BMSCs group had less col agen and more cardiac muscle tissue than BMSCs or H 2 S groups. Left ventricular ejection fraction and left ventricular fractional shortening of the H 2 S-BMSCs group were significantly higher than those of the BMSCs or H 2 S groups (P<0.05). The cells survival rate and cardiac function of myocardial infarction rats can be promoted by H 2 S-preconditioned BMSCs transplantation, which is superior to BMSCs or H 2 S alone.%背景：骨髓间充质干细胞移植可促进心肌修复，治疗心肌梗死，但移植后细胞存活率低等原因制约了其应用与发展。　　目的：探讨硫化氢预处理对骨髓间充质干细胞移植治疗心肌梗死效果的影响。　　方法：从(100±20) g SD大鼠中分离培养骨髓间充质干细胞，第4代时按实验分组处理，移植前2 h给予DAPI标记。将50只体质量(200±20) g雄性SD大鼠分为心肌梗死组和假手术组，心肌梗死组结扎冠状动脉前降支建立心肌梗死模型，假手术组只穿线不结扎，每组10只。模型建立24 h后，分组在梗死心肌周围选择4个点，分别注射生理盐水、骨髓间充质干细胞、硫化氢预处理骨髓间充质干细胞及硫化氢。细胞移植4周后用超声心动图检测心功能指标，Masson染色测定梗死交界区胶原。　　结果与结论：生理盐水组大鼠心肌纤维化严重，梗死区域无心肌组织再生；外源性硫化氢处理后的骨髓间充质干细胞移植组比单用硫化氢或者骨髓间充质干细胞组心肌纤维化程度轻，胶原组织中可见较多心肌细胞再生。硫化氢预处理骨髓间充质干细胞组左室射血分数、左室短轴缩短率显著高于硫化氢组及骨髓间充质干细胞组(P<0.05)。提示硫化氢预处理骨髓间充质干细胞可提高移植后的细胞存活率，改善梗死后心功能，其作用优于单用硫化氢或者骨髓间充质干细胞。