Pin1通过氧化应激诱导大鼠心室重塑的研究
投稿时间:2017-01-08  修订日期:2017-01-08  点此下载全文
引用本文:吴限,李莎,郭芙蓉,黎明江.Pin1通过氧化应激诱导大鼠心室重塑的研究[J].医学研究杂志,2017,46(10):26-30
DOI: 10.11969/j.issn.1673-548X.2017.10.008
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作者单位E-mail
吴限 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
李莎 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
郭芙蓉 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
黎明江 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室 mingjiangli@yahoo.com.cn 
基金项目:国家自然科学基金资助项目(81170085)
中文摘要:目的 讨论肽脯氨酰顺反异构酶Pin1(peptidyl-prolyl isomerase Pin1)与心肌纤维化之间的关系,并验证Pin1是否通过氧化应激参与异丙肾上腺素(isoproterenol,ISO)诱导的大鼠心肌纤维化。方法 30只SD大鼠随机分为空白对照组(A组,8只)、ISO组(B组,13只)以及ISO+胡桃醌(Juglone)组(C组,9只)持续用药4周后取材,行Masson染色观察心肌病理改变和心肌间质胶原纤维增生反应,测定心肌胶原容积分数(collagen volume fraction,CVF);应用活性氧(reactive oxygen species,ROS)荧光探针检测心肌组织氧化活性物质的生成,运用免疫组织化学方法对心肌组织Pin1进行定性定量分析;利用反转录酶-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)技术检测Pin1、Ⅰ型胶原蛋白和Ⅲ型胶原蛋白mRNA表达水平。结果 与A组比较,B组心肌间质胶原增生明显,大量纤维结缔组织将心肌肌束分隔包饶,心肌细胞排列紊乱;CVF明显增高(P < 0.01);此外B组Ⅰ、Ⅲ型胶原蛋白及Pin1 mRNA表达水平高于A组,差异有统计学意义(P < 0.01)。与B相比,C组心肌肌束大体规则,心肌间质及血管旁有少量纤维结缔组织增生;CVF低于B组(P < 0.05);Ⅰ型和Ⅲ型胶原蛋白、Pin1 mRNA表达水平C组低于B组,差异有统计学意义(P < 0.01)。结论 上述结果表明在ISO诱导的大鼠心肌纤维化模型中,Pin1与氧化活性物质的产生有关;加入Pin1特异性抑制剂Juglone后显著减少了氧化活性物质的产生,故尚可认为Pin1可能通过某种机制诱导氧化应激反应参与ISO介导的大鼠心肌纤维化的发生与维持。
中文关键词:心肌纤维化  氧化应激  肽脯氨酰顺反异构酶  胶原蛋白
 
Research of Pin1 in Cardiac Fibrotic Rats Induced by Isoproterenol through Oxidative Stress
Abstract:Objective To explore the possible relationship between peptidyl-prolyl isomerase Pin1 with cardiac fibrosis, and demonstrate whether Pin1 takes part in the development of cardiac fibrosis in rats induced by isoproterenol through oxidative stress. Methods Thirty adults sprague dawley rats were randomly divided into blank control group(n=8,A group), ISO group(n=13,B group), ISO and Juglone group(n=9,C group). The rats were sacrificed 4 weeks later. Masson staining was used to observe rat heart's pathological insults and collagen proliferative reaction in myocardial matrix. CVF was measured by image analysis software. Pin1 in the heart were calculated by immunohistochemistry through the method of combination of qualitative and quantitative analyses. The mRNA levels of Pin1, collagen Ⅰ and collagen Ⅲ were measured by RT-PCR. Results Compared with A group, B group showed that significant proliferation of myocardial interstitial collagen and fibrous connective tissue, the myocardial cells arranged at random, CVF increased significantly (P < 0.01) and the mRNA levels of Pin1, collagen Ⅰ and collagen Ⅲ were obviously increased (P < 0.01). In C group, myocardium were well-arranged and distributed unevenly and orderly, only few fibrous connective tissue around the blood vessels and CVF decreased obviously (P < 0.05). The expression level of Pin1, collagen Ⅰ and collagen Ⅲ was lower than in B group (P < 0.01). Conclusion The results demonstrated that there had a remarkable correlation between Pin1 and oxidative stress, while it was identified that ROS were downregulated after adding Juglone, which is a specific cox inhibitor of Pin1. The present study suggested that Pin1 and oxidative stress may be involved in cardiac fibrosis pathogenesis, with a potential implication as therapeutic targets.
keywords:Cardiac fibrosis  Oxidative stress  Peptidyl-prolyl isomerase Pin1  Collagen
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