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[1]赵晓燕,苏金林.PPARα和TGF-β1调控糜酶促进乳鼠心肌纤维化的信号转导机制研究[J].宁夏医科大学学报,2018,(04):418-423.[doi:10.16050/j.cnki.issn1674-6309.2018.04.010]
 ZHAO Xiaoyan,SU Jinlin.Signal Transduction Mechanism of Myocardial Fibrosis through PPARα and TGF-β1 Induced by Chymase in Neonatal Rat[J].Ningxia Medical University,2018,(04):418-423.[doi:10.16050/j.cnki.issn1674-6309.2018.04.010]
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PPARα和TGF-β1调控糜酶促进乳鼠心肌纤维化的信号转导机制研究(PDF)
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《宁夏医科大学学报》[ISSN:1005-8486/CN:64-1029/R]

卷:
期数:
2018年04期
页码:
418-423
栏目:
论 著
出版日期:
2019-09-30

文章信息/Info

Title:
Signal Transduction Mechanism of Myocardial Fibrosis through PPARα and TGF-β1 Induced by Chymase in Neonatal Rat
作者:
赵晓燕1 苏金林2
(1. 解放军第五医院心内科,银川 750004; 2. 宁夏医科大学总医院心胸外科,银川 750004)
Author(s):
ZHAO Xiaoyan1 SU Jinlin2
(1. Department of Cardiology,the Fifth Hospital of PLA,Yinchuan 750004; 2. Department of Cardiothoracic Surgery,the General Hospital of Ningxia Medical University,Yinchuan 750004)
关键词:
糜酶心肌纤维化信号转导过氧化物酶体增殖物激活受体α转化生长因子-β1
Keywords:
chymasemyocardial fibrosissignal transductionperoxisome proliferator-activated receptor αtransforming growth factor-β1
分类号:
R542.2+3
DOI:
10.16050/j.cnki.issn1674-6309.2018.04.010
文献标志码:
A
摘要:
目的 探讨肥大细胞糜酶促进乳鼠心肌纤维化的主要细胞内信号转导作用机制。方法 采用胰酶消化法分离、培养SD乳鼠的心肌成纤维细胞(CFs),分为对照组、不同浓度糜酶组、糜酶抑制剂(CHI)预处理组和CHI单独作用组。以酶联免疫吸附法(ELISA)测定CFs培养上清Ⅰ、Ⅲ型胶原蛋白含量,逆转录聚合酶链式反应(RT-PCR)检测过氧化物酶体增殖物激活受体α(PPARα)和转化生长因子-β1(TGF-β1)mRNA表达水平,蛋白免疫印迹法(Western blot)检测PPARα和TGF-β1的蛋白表达水平。结果 CFs培养上清Ⅰ、Ⅲ型胶原蛋白含量随糜酶浓度的增加而增加,15、30和 60μg·L-1糜酶组Ⅰ、Ⅲ型胶原蛋白均较对照组升高(P<0.05或<0.01)。糜酶以浓度依赖方式减少CFs的PPARα mRNA和蛋白表达、增加TGF-β1 mRNA和蛋白表达,15、30和60μg·L-1糜酶组与对照组相比差异均有统计学意义(P<0.05或<0.01)。10μmol·L-1 CHI可完全阻断30μg·L-1糜酶诱导的Ⅰ、Ⅲ型胶原合成,并使PPARα mRNA和蛋白表达增加、TGF-β1 mRNA和蛋白表达减少。结论 肥大细胞糜酶可促进乳鼠心肌纤维化,其细胞内信号转导机制与PPARα mRNA和蛋白表达下调、TGF-β1 mRNA和蛋白表达上调有关。
Abstract:
Objective To investigate the intracellular signal transduction of myocardial fibrosis induced by mast cell chymase in neonatal rat. Methods Cultured cardiac fibroblasts(CFs) of neonatal SD rats were isolated by trypsinization. They were devided into control group, different concentration chymase groups, pretrentment with chymase inhibitor(CHI) group and CHI group. The Type Ⅰ and Type Ⅲ collagen contents in cultured supernatants of CFs were evaluated by ELISA. The mRNA expressions of peroxisome proliferator-activated receptor α(PPARα) and transforming growth factor-β1(TGF-β1) in CFs were determined by RT-PCR. Western blot was used to measure the protein expressions of PPARα and TGF-β1. Results 15,30 and 60μg·L-1 chymase remarkably increased Type Ⅰ and Type Ⅲ collagen, respectively,both in a concentration-dependent manner compared with those of the controls(P<0.05 or <0.01). Chymase obviously decreased the PPARα,increased the TGF-β1 mRNA and protein expressions,in a dose-dependent manner. The PPARα,TGF-β1 mRNA and protein stimulated by 15,30 and 60μg·L-1 chymase were significantly different from those of the controls(P<0.05 or <0.01). Tratment with CHI could completely block the synthesis of type I and III collagen induced by 30?滋g·L-1 chymase, and increase the expression of PPARα mRNA and protein,and decrease the expression of TGF-β1 mRNA and protein. Conclusions Mast cell chymase can induce myocardial fibrosis in neonatal rat. The intracellular signal transduction is associated with the downregulation of PPARα and upregulation of TGF-β1 mRNA and protein.

参考文献/References:


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备注/Memo

备注/Memo:
收稿日期:2018-01-09
基金项目:全军医药卫生科研基金资助课题(914031)
作者简介:赵晓燕,女(回族),主任医师,医学博士,从事心肌纤维化的发病机制及防治研究。E-mail:zxysxy420@163.com
更新日期/Last Update: 2018-04-30