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-βNon-classical Pathway Against Myocardial Fibrosis in Rats

作　　者：夏文庆 袁向珍[2] 路怀志 柳杨 杜大勇 李运田 XIA Wen-qing;YUAN Xiang-zhen;LU Huai-zhi;LIU Yang;DU Da-yong;LI Yun-tian(The Second School of Clinical Medicine,Southern Medical University/Centre of Coronary Heart Disease,the 305 Hospital of People's Liberation Army,Beijing 100017,China;Health Care Institute of Affiliated Hospital of Inner Mongolia Medical University,Huhhot 010050,China;Department of Cardiology,Ningling County People's Hospital,Shangqiu 476700,China)

机构地区：[1]南方医科大学第二临床医学院/中国人民解放军第三〇五医院心脏中心,北京100017 [2]内蒙古医科大学附属医院保健所,呼和浩特010050 [3]宁陵县人民医院心血管内科,商丘476700

出　　处：《四川大学学报（医学版）》2020年第3期344-349,共6页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.81560045)资助。

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。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 colonystimulating 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 typeⅢcollagen 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.

关 键 词：异丙肾上腺素 G-CSF 心肌纤维化 TGF-Β 

分 类 号：R542.2[医药卫生—心血管疾病]