中国组织工程研究

中国组织工程研究 ›› 2015, Vol. 19 ›› Issue (24): 3844-3848.doi: 10.3969/j.issn.2095-4344.2015.24.014

• 组织构建与生物活性因子 tissue construction and bioactive factors • 上一篇    下一篇

部分肝切除肝再生过程中肝细胞生长因子激活因子抑制因子1，2的表达

 杨  龙1，张雅敏1，崔子林1，刘子荣2，杨  超2   

  1. 1Department of Hepatobiliary Surgery, Tianjin First Center Hospital, Tianjin 300192, China; 
    2First Center Clinical Institute, Tianjin Medical University, Tianjin 300192, China
  • 出版日期:2015-06-11 发布日期:2015-06-11
  • 通讯作者: 张雅敏，博士，主任医师，天津市第一中心医院肝胆外科，天津市 300192
  • 作者简介:杨龙，男，1988年生，山东省淄博市人，汉族， 2014年天津医科大学毕业，硕士，医师，主要从事肝胆外科临床及肝再生研究方面的工作。
  • 基金资助:

    天津市应用基础与前沿技术研究计划(14JCYBJC24800)；国家自然科学基金(81370576)

The expression of hepatocyte growth factor activator inhibitors 1 and 2 during liver regeneration after partial hepatectomy

Yang Long1, Zhang Ya-min1, Cui Zi-lin1, Liu Zi-rong2, Yang Chao2   

  1. 1天津市第一中心医院肝胆外科，天津市  300192；
    2天津医科大学一中心临床学院，天津市  300192
  • Online:2015-06-11 Published:2015-06-11
  • Contact: Zhang Ya-min, M.D., Chief physician, Department of Hepatobiliary Surgery, Tianjin First Center Hospital, Tianjin 300192, China
  • About author:Yang Long, Master, Physician, Department of Hepatobiliary Surgery, Tianjin First Center Hospital, Tianjin 300192, China
  • Supported by:

    Program of Application Foundation and Advanced Technology of Tianjin, No. 14JCYBJC24800; the National Natural Science Foundation of China, No. 81370576

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摘要：

 背景：有研究表明肝硬化个体在行肝部分切除后肝再生较健康肝脏缓慢的原因可能与其肝再生过程中的肝细胞生长因子的合成分泌延迟及活性降低有关，但导致这一现象的原因尚不明确，近年来发现的肝细胞生长因子激活因子的抑制因子(hepatocyte growth factor activator inhibitor，HAI)能够间接地抑制肝细胞生长因子的激活，但是鲜有研究探索HAI的抑制因子在肝硬化肝脏行部分肝切除后肝再生过程中的表达情况及其与肝再生的关系。
目的：通过建立肝硬化大鼠部分肝切除模型来研究HAI的抑制因子1，2(HAI-1，HAI-2)在硬化和正常肝脏再生中的表达情况，探讨HAI-1，HAI-2在硬化肝脏部分肝切除后的生物学效应及其与肝再生的关系。
方法：采用体积分数40% 四氯化碳油溶液背部皮下注射法建立大鼠肝硬化模型，对实验组进行70%肝脏切除术建立再生模型，对照组大鼠仅给予普通饲料饮水喂养并行70%肝脏切除。分别于术前及术后3，6，12，24，48 h麻醉处死大鼠并留取脾脏标本检测。采用RT-PCR技术检测脾源性HAI-1，HAI-2 mRNA的表达情况。
结果与结论：两组大鼠部分肝切除后HAI-1 mRNA的表达均呈现出先升高后降低的趋势，而肝硬化大鼠HAI-1 mRNA表达量持续高于对照组(P < 0.05)，两组大鼠之间HAI-2 mRNA表达量差异无显著性意义(P > 0.05)。说明肝硬化大鼠部分肝切除后再生过程中HAI-1 mRNA的表达持续高于健康大鼠，这可能导致了肝硬化大鼠肝细胞生长因子激活因子合成分泌不足，从而使得肝细胞生长因子前体活化不足，最终引起肝再生缓慢。HAI-2并没有参与肝脏的损伤修复进程。

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 组织构建, 组织工程, 肝再生, 肝细胞生长因子激活因子抑制因子, 肝细胞生长因子激活因子, 肝细胞生长因子, 肝硬化, 大鼠, 部分肝切除, 四氯化碳, 基因表达, 返转录聚合酶链反应, 国家自然科学基金

Abstract:

BACKGROUND: Studies have shown that the reason of the slower liver regeneration in individuals of cirrhotic liver after partial hepatectomy compared with healthy liver may be related to the delayed synthesis and secretion of hepatocyte growth factor during liver regeneration, but the cause of this phenomenon is not clear. The hepatocyte growth factor activator inhibitor found in recent years can indirectly inhibit the activation of hepatocyte growth factor, but there is little research to explore the expression of hepatocyte growth factor activator inhibitor in the regeneration process after partial hepatectomy in cirrhotic liver and its relationship with the liver regeneration.
OBJECTIVE: To investigate the expression of hepatocyte growth factor activator inhibitors (HAI-1, HAI-2) during cirrhotic and normal liver regeneration after partial hepatectomy through establishing the cirrhotic rat model, and to explore the biological effects of HAI-1, HAI-2 in cirrhotic liver during the liver regeneration after partial hepatectomy.
METHODS: We used 40% CCl4 subcutaneous injection to establish the cirrhotic rat model, then we performed 70% liver resection for the experimental group. The rats in the control group only received ordinary water feeding and 70% liver resection. Rats in each group were randomly sacrificed before surgery and at 3 hours, 6 hours, 12 hours, 24 hours and 48 hours after surgery, and samples were collected. We used RT-PCR technology to detect the expression of HAI-1 mRNA, HAI-2 mRNA in splenic tissue.
RESULTS AND CONCLUSION: The expression levels of HAI-1 mRNA of two groups after partial hepatectomy were increased firstly and then decreased. The expression of HAI-1 mRNA in cirrhotic rats was sustained higher than that of the control group (P < 0.05), there was no significant difference between the two groups of the expression of HAI-2 mRNA (P > 0.05). The expression of HAI-1 mRNA in liver cirrhosis rats after resection was consistently higher than that in healthy rats, which may lead to the insufficient synthesis and secretion of hepatocyte growth factor activator in cirrhotic rats, then hepatocyte growth factor precursor may not be activated enough, eventually leading to slow liver regeneration. HAI-2 may not be involved in the wound repair process of liver. 

 

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