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经冠状动脉注射法自体骨骼肌成肌细胞移植治疗兔急性心肌梗死

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第2期
页码:
179
栏目:
基础研究
出版日期:
2009-03-30

文章信息/Info

Title:
Treating acute myocardial infarction with autologus skeletal myoblast transplantation by intracoronary-infusion in rabrits
作者:
朱红1; 宋湘2; 金丽娟2; 金鹏2; 刘娴2; 李学奇2
1.首都医科大学宣武医院综合科，北京 100053； 2.哈尔滨医科大学附属第四医院心内科，黑龙江 哈尔滨 150001
Author(s):
ZHU Hong1;  SONG Xiang2;  JIN Li-juan2;  JIN-Peng2;  LIU Xian2;  LI Xue-qi2
1.Department of Combined treatment, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053, China; 2.Department of Cardiovascular Medicine, Fourth Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang, China
关键词:
心肌梗死; 成肌细胞; 细胞移植; 冠状血管
Keywords:
myocardial Infarction;  skeletal myoblasts;  cell transplantation;  coronary vessel
分类号:
R542.22
DOI:
-
文献标识码:
A
摘要:
目的 观察经冠状动脉注射自体骨骼肌成肌细胞（SM）移植到兔急性心肌梗死（AMI）区后的生长分化特点和疗效。方法 取日本大耳白兔45只，随机分为经冠脉注射SM移植组、对照组和假手术组，各15只。SM移植组取臀肌分离、纯化SM并体外扩增。结扎兔左冠脉前降支（LAD），建立AMI模型。再灌注后，SM移植组经冠脉注射自体SM悬液1 ml(5×106个细胞)。对照组以相同的方法建立AMI模型，注入等量的无血清培养液。假手术组除不结扎左前降支外，其余操作均同对照组。4周后，通过HE 染色和抗5-溴脱氧尿核苷（BrDU）抗体、抗骨骼肌特异性慢β-肌凝蛋白重链（slow-MHC）抗体的免疫组化染色评价移植细胞的转归。术后24 h和4周，以超声心动图仪测量3组的左室射血分数（LVEF） 和左室短轴缩短率（FS）。结果 SM移植组在术后4周，HE染色后可在梗死区内找到新生的多核肌样细胞。抗BrdU 抗体和抗Slow-MHC抗体的免疫组化染色呈阳性。术后24 h，假手术组的LVEF 和FS 明显高于对照组和SM移植组（P<0.01）。而术后4周，与对照组比较，假手术组和SM移植组的LVEF和FS明显改善（P<0.01）。结论 经冠脉注射法移植自体SM可在AMI区存活，修复受损心肌并提高心脏的功能。
Abstract:
AIM To observe the growth, differentiation and curative effect of autologus skeletal myoblasts (SM) following their transplantation into acute myocardial infarction(AMI) region by intracoronary infusion. METHODS Forty-five white Japanese big-ear rabbits were randomly divided into three groups: SM group, control group and sham operation group, with 15 animals were in each group. Gluteus were obtained for SM separation, purification and expansion in vitro. AMI model was obtained by ligating the coronary artery left anterior descending branch (LAD). 5×106 Bromodeoxy uridine(BrdU) labeled SM were infused into LAD after reperfusion. Equal serum-free medium alone was infused into control group after the ligation of the LAD. Except for the LAD ligation, sham operation group underwent the same procedures as control group. HE stain and anti-BrdU, anti-myosin-heavy chain(MHC, slow) immunohistochemistry stain were performed to evaluate the differentiation of the transplanted cells 4 weeks after transplantation. Left ventricle ejection fraction (LVEF) and shortening fraction (FS) were measured by echocardiography 24 hours and 4 weeks after transplantation. RESULTS Four weeks after transplantation, multinucleate muscle cells were seen in the MI region of the SM group by HE stain, and anti-BrdU and anti-MHC (slow) antibody immunohistochemistry showed positive. Twenty-four hours after transplantation, the LVEF and FS of animals in the sham operation group were better than those in SM and control group (P<0.01). Four weeks after transplantation, the LVEF and FS of animals in SM group and sham operation group were better than those in control group (P<0.01). CONCLUSION Autologus SM transplanted into AMI region by intracoronary infusion can survive in the AMI region, repairing the impaired myocardium and improving the cardiac function.

参考文献/References

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［2］ 刘娴, 王晓云. 骨骼肌卫星细胞移植治疗心肌梗死的研究进展［J］. 心脏杂志, 2006, 18(3):353-355.

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［5］ Pagani FD, DerSimonian H, Zawadzka A, et al. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation［J］. J Am Coll Cardiol, 2003, 41(5):879-888.

［6］ Taylor DA, Silvestry SC, Bishop SP, et al. Delivery of primary autologous skeletal myoblasts into rabbit heart by coronary infusion: a potential approach to myocardial repair［J］. Proc Assoc Am Physicians, 1997, 109(3):245-253.

［7］ Smits PC, van Geuns RJ, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up［J］. J Am Coll Cardiol, 2003, 42(12):2063-2069.

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［9］ Scorsin M, Hagege A, Vilquin JT, et al. Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function［J］. J Thorac Cardiovasc Surg, 2000, 119(6):1169-1175.

［10］Formigli L, Perna AM, Meacci E, et al. Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling［J］. J Cell Mol Med, 2007, 11(5):1087-1100.

备注/Memo

备注/Memo:
收稿日期：2008-4-28.基金项目：黑龙江省自然科学基金项目资助（ZJY04-03）;黑龙江省博士后启动基金资助（LRZ-05023） 通讯作者：李学奇，主任医师，主要从事冠心病的研究Email：lixueqi@medmail.com.cn 作者简介：朱红，医师，博士Email:zhuh4085@126.com
更新日期/Last Update: 2009-04-16