摘要
背景:骨髓间充质干细胞静脉移植后,能否归巢至心脏受损部位和分化为心肌样细胞尚无统一定论。目的:探讨重组人生长激素联合骨髓间充质干细胞静脉移植对充血性心肌病大鼠心肌和血管新生的影响。方法:密度梯度离心和贴壁筛选法获得大鼠骨髓间充质干细胞。模型组、细胞移植组、生长激素组、联合组大鼠均在阿霉素诱导下建立心脏衰竭模型。造模后,细胞移植组经静脉注入BrdU标记的骨髓间充质干细胞8×1013L-1;生长激素组皮下注射重组人生长激素2U/(kg·d),连续14d;联合组行骨髓间充质干细胞移植与重组人生长激素注射。4周后取材,BrdU+MHC及BrdU+Actin免疫组化染色确定骨髓间充质干细胞的归巢情况,评价移植细胞向心肌样细胞和血管内皮细胞的分化,苏木精-伊红染色检测血管密度。结果与结论:与细胞移植组比较,联合组BrdU免疫组化阳性率显著升高(P<0.001);BrdU+MHC双染和BrdU+Actin双染后心肌样细胞、血管内皮细胞均显著增多(P<0.001)。与模型组比较,生长激素组、细胞移植组、联合组的总血管密度、微血管密度、毛细血管密度均显著升高(P<0.001),后3组间比较无明显差异(P>0.05)。结果证实骨髓间充质干细胞静脉移植后可归巢到心脏,对充血性心肌病大鼠心肌和血管有明显修复作用,能在损伤处区存活、生长,并向心肌样细胞、血管内皮细胞方向分化,增加损伤处血管密度;生长激素可以改善微环境,加强骨髓间充质干细胞向心肌样细胞、血管内皮细胞的转化率。
BACKGROUND： It is controversial whether bone marrow mesenchymal stem calls can retain in cardiac injured position, or differentiate into cardiomyocytes or not. OBJECTIVE： To study the effects of recombinant human growth hormone and bone marrow mesenchymal stem calls （BMSCs） intravenous transplantation on myocardium and angiogenesis in rats with congestive cardiomyopathy. METHODS： BMSCs were collected from rats by density gradient cantrifugation and adhesive-screening method. Models of cardiac failure were established using adriamycin induction in the model, cell transplantation, growth hormone and combination groups. Following model establishment, cell transplantation group received BrdU-labeled BMSCs （8×1013/L） via vein. Growth hormone group underwent subcutaneous injection of human growth hormone 2 U/kg per day, for 14 consecutive days. Combination group received injection of human growth hormone and BMSC transplantation, At week 4, samples were collected. Immunohistochemical staining for BrdU＋MHC and BrdU＋Actin was used to determine homing of BMSCs to evaluate the differentiation of transplanted calls into cardiomyocytes and vascular endothelia cells. Hematoxylin-eosin staining was utilized to detect vascular density. RESULTS AND CONCLUSION： Compared with the cell transplantation group, positive rate of Brdu immunohistochemistry was increased in the combination group （P 〈 0.001 ）. The number of cardiomyocytes and vascular endothelia calls was significantly increased following Brdu＋MHC and Brdu＋Actin staining （P 〈 0.001）. Compared with the model group, total vascular density, microvessel density and capillary density were significantly increased in the growth hormone, cell transplantation and combinatior groups （P 〈 0.001 ）. No significant difference was determined among growth hormone, call transplantation and combination groups （P 〉 0.05）. intravenous transplantation of BMSCs could repair cardiomyocytes and vascular endothelial cells by homing into the heart. BMSCs could survive in damaged area and differentiate into cardiomyocytes or vascular endothelial cells and increase the vascular density significantly. Growth hormone could improve microenvironment and raise rates of differentiating into cardiomyocytes or vascular endothelial cells.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2010年第6期1064-1067,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
山西省高校科研开发项目(200811073)
山西医科大学博士科题~~
