中国组织工程研究

中国组织工程研究 ›› 2015, Vol. 19 ›› Issue (36): 5774-5781.doi: 10.3969/j.issn.2095-4344.2015.36.007

• 骨髓干细胞 bone marrow stem cells • 上一篇    下一篇

不同治法中药干预心肌梗死边缘区归巢骨髓间充质干细胞的增殖与分化

张金生1，张宝霞2，张阳阳1，朱慧芳1   

  1. 1河南中医学院第三附属医院，河南省郑州市  450000； 2河南中医学院第一附属医院，河南省郑州市  450008
  • 出版日期:2015-09-03 发布日期:2015-09-03
  • 通讯作者: 张宝霞，硕士，副主任医师，河南中医学院第一附属医院，河南省郑州市 450008
  • 作者简介:张金生，男，1972年生，河南省许昌市人，汉族，2006年上海中医药大学毕业，博士/博士后，主任医师，主要从事中医药防治老年病的基础与临床研究。
  • 基金资助:

    2011年国家自然基金面上项目(81072798/H2708)：动员骨髓间充质干细胞“归巢”在心梗后心肌重塑中的作用及活血化瘀法干预研究

Interventional effects of different Chinese medicine therapies on proliferation and differentiation of bone marrow mesenchymal stem cells homing to the border zone of myocardial infarction 

Zhang Jin-sheng1, Zhang Bao-xia2, Zhang Yang-yang1, Zhu Hui-fang1   

  1. 1Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China; 2First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450008, Henan Province, China
  • Online:2015-09-03 Published:2015-09-03
  • Contact: Zhang Bao-xia, Master, Associate chief physician, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450008, Henan Province, China
  • About author:Zhang Jin-sheng, M.D., Chief physician, Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81072798/H2708

PDF

337

被引次数

5

摘要：

背景：明确各种干细胞向心肌细胞分化过程中的表达变化，确定分化后的干细胞在心功能活动中发挥生理作用，并通过某些特定的条件刺激干细胞的增殖潜能，使其直接分化成功能性心肌细胞，补充缺失的心肌细胞，有效地抑制心脏肌成纤维细胞过度增殖，是心血管疾病再生治疗的新方法和思路。
目的：探讨三七总皂苷、红景天苷、黄芪有效组分对心肌梗死大鼠内源性CD105阳性骨髓间充质干细胞归巢及增殖分化的影响。
方法：急性心肌梗死模型大鼠随机分为活血组、益气组、益气活血组、模型组，各组再按1，3，7，14，28 d时间点分为亚组，以未造模的正常大鼠为正常组。根据体表面积剂量换算法计算给药量，活血组给予80 g/L血塞通软胶囊(主要成分为三七总皂苷)、益气组给予0.5 g/mL黄芪颗粒、益气活血组给予70 g/L诺迪康胶囊(主要成分为红景天苷)灌胃，大鼠按每100 g体质量灌胃1 mL药液，正常组和模型组以等量生理盐水灌胃，1次/d，共28 d。免疫组化法检测不同时间点梗死边缘区CD105、CD117、Vimentin(波形蛋白)、cTnT(心肌肌钙蛋白T)、GATA-4(锌指转录因子4)、Ki-67阳性细胞数。

结果与结论：①模型组CD105、CD117、cTnT、GATA-4、Ki-67表达高于正常组，且CD105、CD117、cTnT、GATA-4、Ki-67表达在1-7 d有增多趋势，7 d达到高峰，其后降低；活血组、益气活血组、益气组各时间点CD105、CD117、cTnT、GATA-4 、Ki-67阳性细胞数比模型组增多明显(P < 0.05)，但活血组增多趋势优于益气活血组、益气组；各组Ki-67与CD105、CD117、cTnT、GATA-4染色结果不完全平行，但增长趋势大致一致。②模型组Vimentin表达高于正常组，Vimentin在1-3 d有增多趋势，3 d达到高峰，其后降低；活血组、益气活血组、益气组各时间点Vimentin阳性细胞数比模型组减少(P < 0.05)；活血组Vimentin阳性细胞数少于益气活血组、益气组(P < 0.05)；活血化瘀方药对Vimentin降低最明显，说明活血组抗纤维化作用效果显著。结果表明三七总皂苷、红景天皂苷、黄芪有效组分均可促进骨髓间充质干细胞增殖分化防治心肌梗死后心肌重塑，但活血化瘀方药效果最明显。

 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

 

关键词: 干细胞, 骨髓干细胞, 三七总皂苷, 红景天苷, 黄芪有效组分, 骨髓间充质干细胞, 心肌梗死, 国家自然基金

Abstract:

BACKGROUND: New ideas for regenerative treatment of cardiovascular disease are as follows: to understand the changes in all kinds of stem cells differentiating into cardiomyocytes, to determine the physiological role of differentiated stem cells in cardiac functional activities, to stimulate the proliferative potential of various stem cells under certain conditions that can directly differentiate into functional cardiomyocytes, thereby replenishing deficient cardiomyocytes and effectively inhibiting excessive proliferation of fibroblasts.
OBJECTIVE: To investigate the effects of panax notoginseng saponins, salidroside and astragalus effective components on the homing, proliferation and differentiation of endogenous CD105-positive bone marrow mesenchymal stem cells of myocardial infarction rats.
METHODS: Acute myocardial infarction rats were randomly divided into activating blood circulation group, tonifying qi group, activating blood circulation+tonifying qi group (combined group), model group. Normal rats served as control group. The former three groups were orally given 80 g/L Xuesaitong soft capsules (panax notoginseng saponins as the main component), 0.5 g/mL astragalus particles and 70 g/L Nuodikang capsules (salidroside as the main component), respectively, at a dose of 1 mL/100 g, once a day, totally for 28 days. The control and model groups were given the same volume of normal saline. Expressions of CD105, CD117, vimentin, cardiac troponin T (cTnT), zinc finger transcription factor 4 (GATA-4) and Ki-67 were detected using immunohistochemical method at 1, 3, 7, 14, 28 days of drug administration.
RESULTS AND CONCLUSION: (1) Compared with the control group, the expressions of CD105, CD117, cTnT, GATA-4 and Ki-67 were higher in the model group, which were increased at 1-7 days, peaked at 7 days, and then decreased. Compared with the model group, the expressions of CD105, CD117, cTnT, GATA-4 and Ki-67 were significantly higher in the activating blood circulation group, tonifying qi group and combined group, especially in the activating blood circulating group, at different time of drug administration (P < 0.05). In each group, the staining results of Ki-67 were not exactly parallel to those of CD105, CD117, cTnT and GATA-4, but their rising tendency was substantially the same. (2) Compared with the control group, the vimentin expression in the model group was higher, which showed an increasing tend at 1-3 days, peaked at 3 days and then declined. Compared with the model group, the vimentin expression was significantly lower in the activating blood circulation group, tonifying qi group and combined group, especially in the activating blood circulating group, at different time of drug administration (P < 0.05). It suggested that the activating blood circulation group had a remarkable antifibrotic role. These findings indicate that panax notoginseng saponins, salidroside and astragalus effective components all can promote the proliferation and differentiation of bone marrow mesenchymal stem cells to delay myocardial remodeling, but the recipe for promoting blood circulation has the most obvious outcomes. 

 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Myocardial Infarction, Bone Marrow, Mesenchymal Stem Cells, Panax notoginseng, Rhodiola, Astragalus membranaceus

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