骨髓干细胞动员抑制TGF-β非经典通路对抗大鼠心肌纤维化的研究

夏文庆; 袁向珍; 路怀志; 柳杨; 杜大勇; 李运田

doi:10.12182/20200560503

骨髓干细胞动员抑制TGF-β非经典通路对抗大鼠心肌纤维化的研究

Mobilization of Bone Marrow Mesenchymal Stem Cells Inhibits TGF-β Non-classical Pathway Against Myocardial Fibrosis in Rats

摘要

摘要:
目的探讨骨髓干细胞动员抑制大鼠心肌纤维化的机制与转化生长因子（TGF-β）介导的非经典通路的关系。
方法 22只Wistar大鼠通过皮下注射异丙肾上腺素（isoproterenol，Iso)建立心肌纤维化模型后，随机分为对照组（Con组）和动员组（GT组），GT组大鼠皮下注射重组人粒细胞刺激因子(rhG-CSF)，连续注射5 d，对照组同期皮下注射生理盐水。末次注射4周后，行HE和Masson染色观察两组大鼠心肌结构，ELISA法检测血清B型利钠肽（BNP）质量浓度，免疫组化染色观察心肌组织中Ⅲ型胶原表达，Western blot检测组织Ⅰ型胶原、TGF-β、转化生长因子激酶1( TAK1 )、丝裂原活化蛋白激酶激酶(MKK)、p38丝裂原活化蛋白激酶(p38MAPK)的蛋白水平。
结果与对照组相比，GT组大鼠血清BNP质量浓度降低(P<0.01)；Masson染色胶原沉积减少，胶原面积比值下降(P<0.01)；Western blot检测Ⅰ型胶原、TGF-β、TAK1、MKK3、p38MAPK表达较对照组均降低（P<0.05）。
结论骨髓干细胞动员可改善大鼠心肌纤维化的程度，这种抗心肌纤维化的作用与抑制TGF-β/TAK1/MKK/p38MAPK通路有关。

Abstract:
Objective To observe the relationship between the mechanism of bone marrow stem cell mobilization mediated the myocardial fibrosis inhibition in rats and the non-classical pathway mediated by transforming growth factor-β (TGF-β).
Methods Twenty two Wistar rats were subcutaneously injected with isoproterenol (Iso) to establish the model of myocardial fibrosis, and then were randomly divided into control group and granulocyte colony-stimulating factor (G-CSF)-treat group (GT group). The rats in GT group were subcutaneously injected with recombinant human granulocyte stimulating factor for 5 days, and the control group was injected with normal saline. After 4 weeks, the myocardial structure was observed by pathological staining, the content of serum B type natriuretic peptide (BNP) was detected by ELISA , the expression of type Ⅲ collagen was detected by immunohistochemistry staining and the protein expression level of typeⅠcollagen, TGF-β, transforming growth factor kinase 1 (TAK1), mitogen-activated protein kinase kinase (MKK) and p38 mitogen-activated protein kinase (p38MAPK) was determined by Western blot.
Results Compared with the control group, the serum BNP level, Masson staining collagen deposition, collagen area ratio and the expression of typeⅠcollagen, TGF- β, TAK1, MKK3 and p38MAPK in the GT group were lower than those in the control group.
Conclusion Bone marrow stem cell mobilization can alleviate the degree of myocardial fibrosis in rats, which is related to the inhibition of TGF- β/TAK1/MKK/p38MAPK pathway.

HTML全文

参考文献(20)

施引文献

资源附件(0)

开放获取 本文遵循知识共享署名—非商业性使用4.0国际许可协议（CC BY-NC 4.0），允许第三方对本刊发表的论文自由共享（即在任何媒介以任何形式复制、发行原文）、演绎（即修改、转换或以原文为基础进行创作），必须给出适当的署名，提供指向本文许可协议的链接，同时标明是否对原文作了修改；不得将本文用于商业目的。CC BY-NC 4.0许可协议详情请访问 https://creativecommons.org/licenses/by-nc/4.0