IGFBP-3在大鼠心肌纤维化和心肌成纤维细胞活化增殖中的表达  

Expression of IGFBP-3 in rat myocardial fibrosis and activation and proliferation of cardiac fibroblasts

作　　者：宋剑南 陶辉[1,2] 丁季飞 徐盛松[1,2] 石开虎[1,2] Song Jiannan;Tao Hui;Ding Jifei(Dept of Cardiothoracic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601;Cardiovascular Research Center, Anhui Medical University, Hefei 230601)

机构地区：[1]安徽医科大学第二附属医院心胸外科,合肥230601 [2]安徽医科大学心血管病研究中心,合肥230601

出　　处：《安徽医科大学学报》2020年第2期263-268,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81570295);安徽省自然科学基金(编号:1808085MH231)。

摘　　要：目的探究胰岛素样生长因子结合蛋白-3(IGFBP-3)在大鼠心肌纤维化和心肌成纤维细胞(CFs)活化增殖中的表达变化。方法用40只SD大鼠随机等分成模型组和对照组,模型组大鼠用皮下注射异丙肾上腺素的方式建立心肌组织纤维化模型,对照组注射等质的生理盐水。用转化生长因子β1(TGF-β1)刺激乳鼠CFs,使其增殖活化制备细胞模型作为模型组,对照组为未经任何刺激正常培养等时长的CFs。大鼠心肌组织纤维化模型运用HE和Masson染色检测病理变化,用CCK-8测定CFs增殖活化程度,分别用qRT-PCR、Western blot检测IGFBP-3、α-平滑肌肌动蛋白(α-SMA)和Ⅰ型胶原前胶原A1(COL1A1)的mRNA和蛋白表达情况。结果与对照组比较,动物模型组中心肌组织胶原纤维增生,心肌细胞排列紊乱,细胞模型组中加入TGF-β1刺激后CFs增殖活化明显。在动物和细胞模型组中与对照组相比,IGFBP-3、α-SMA和COL1A1的蛋白和mRNA的表达显著增高。结论IGFBP-3在纤维化心肌和加入TGF-β1刺激后的CFs中表达明显升高,提示IGFBP-3在心肌纤维化病变过程中可能存在促进或抑制作用,有助于探索心肌纤维化的病理机制。Objective To investigate the expression changes of insulin-like growth factor binding protein-3(IGFBP-3)in rat myocardial fibrosis and cardiac fibroblasts(CFs)activation and proliferation.Methods Forty SD rats were randomly divided into model group and control group.The model group rats were subcutaneously injected with isoproterenol to establish a model of myocardial tissue fibrosis.Transforming growth factorβ1(TGF-β1)was used to stimulate the CFs of neonatal rats to make them proliferate and activate as a model group.The control group was CFs that were cultured normally without any stimulation.The rat myocardial tissue fibrosis model was used to detect pathological changes using HE and Masson staining,CCK-8 was used to determine the degree of CFs proliferation and activation,and qRT-PCR and Western blot were used to detect IGFBP-3 andα-smooth muscle actin(α-SMA)and type I collagen procollagen A1(COL1A1)mRNA and protein expression.Results Compared with the control group,myocardial tissue collagen fibers proliferated and myocardial cells were disordered in the animal model group.CFs stimulated by TGF-β1 in the cell model group had significant proliferation and activation.Compared with the control group,the protein and mRNA expressions of IGFBP-3,α-SMA and COL1A1 were significantly increased in the animal and cell model groups.Conclusion The expression of IGFBP-3 in fibrotic myocardium and CFs stimulated by TGF-β1 is significantly increased,suggesting that IGFBP-3 may promote or inhibit myocardial fibrotic lesions,which may be helpful to explore the pathological mechanism of myocardial fibrosis.

关 键 词：胰岛素样生长因子结合蛋白-3 心肌纤维化 心肌成纤维细胞 Ⅰ型胶原 增殖 转化生长因子β1 

分 类 号：R542.23[医药卫生—心血管疾病]