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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

发布时间:2018-10-10 18:59
【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 mR NA的表达情况。结果与结论:两组大鼠部分肝切除后HAI-1 mR NA的表达均呈现出先升高后降低的趋势,而肝硬化大鼠HAI-1mR NA表达量持续高于对照组(P0.05),两组大鼠之间HAI-2 mRNA表达量差异无显著性意义(P0.05)。说明肝硬化大鼠部分肝切除后再生过程中HAI-1 mR NA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。
[Abstract]:Background: studies have shown that the slow regeneration of liver after partial hepatectomy may be related to the delayed synthesis and secretion of hepatocyte growth factor (HGF) and decreased activity of hepatocyte growth factor (HGF) during liver regeneration in cirrhotic individuals. However, the cause of this phenomenon is not clear. Recently, the inhibitor of hepatocyte growth factor activator (hepatocyte growth factor activator inhibitor,HAI) can indirectly inhibit the activation of hepatocyte growth factor. However, few studies have explored the expression of HAI inhibitor in liver regeneration after partial hepatectomy in cirrhotic liver and its relationship with liver regeneration. Objective: to study the expression of HAI inhibitor 1t2 (HAI-1,HAI-2) in sclerosing and normal liver regeneration in cirrhotic rats by establishing partial hepatectomy model, and to investigate the biological effect of HAI-1,HAI-2 after partial hepatectomy and its relationship with liver regeneration. Methods: the cirrhotic model of rats was established by subcutaneous injection of 40% carbon tetrachloride oil solution. The regenerative model was established by 70% hepatectomy in the experimental group and 70% hepatectomy was performed in the control group. The rats were anesthetized for 48 hours before and after operation. The expression of splenic HAI-1,HAI-2 mR NA was detected by RT-PCR technique. Results and conclusion: after partial hepatectomy, the expression of HAI-1 mR NA in the two groups increased first and then decreased, while the expression of HAI-1mR NA in cirrhotic rats was higher than that in the control group (P0.05). There was no significant difference in the expression of HAI-2 mRNA between the two groups (P0.05). The results suggest that the expression of HAI-1 mR NA in liver cirrhosis rats is higher than that in healthy rats after partial hepatectomy, which may lead to insufficient synthesis and secretion of hepatocyte growth factor activator in cirrhotic rats. As a result, the precursor of hepatocyte growth factor was not activated enough, resulting in slow liver regeneration. HAI-2 did not participate in the process of liver injury and repair.
【作者单位】: 天津市第一中心医院肝胆外科;天津医科大学一中心临床学院;
【基金】: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)~~
【分类号】:R657.3

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