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| 乙酰肝素酶调控大鼠肝再生机制探讨 |
| 张友磊1△,韩秋成2△,卢文峰1,付雍1,朱楠1,杨宁1,杨广顺1* |
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(1. 第二军医大学东方肝胆外科医院肝外五科, 上海 200438;
2. 上海交通大学医学院仁济医院南院肿瘤介入科, 上海 201112
△共同第一作者
*通信作者) |
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| 摘要: |
| 目的 探讨乙酰肝素酶（HPSE）调控大鼠肝再生的机制。方法 设计合成HPSE小干扰RNA（siRNA），以in vivo-jetPEI-Gal为载体转染70%肝切除大鼠，转染后免疫组化检测大鼠肝组织肝细胞生长因子（HGF）和血管内皮生长因子（VEGF）蛋白的表达，蛋白质印迹法检测肝组织基质金属蛋白酶（MMP）-2和MMP-9蛋白的表达，Ⅷ因子免疫组化检测肝组织微血管密度（MVD）。结果 使用siRNA干扰HPSE后，大鼠肝组织中HGF、VEGF蛋白的表达降低，MVD降低，MMP-2和MMP-9表达降低，差异均有统计学意义（P<0.01）。结论 HPSE可通过释放激活细胞外基质（ECM）中的HGF促进肝细胞增殖、增加VEGF的表达加速血管生成以及上调MMP-2和MMP-9的表达等途径调控大鼠肝再生。 |
| 关键词: 乙酰肝素酶 小分子干扰RNA 肝切除术 肝脏再生 |
| DOI：10.16781/j.0258-879x.2016.12.1459 |
| 投稿时间：2016-07-17修订日期：2016-09-01 |
| 基金项目:上海市自然科学基金（10ZR1439700）. |
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| Role of heparanase in regulating rat liver regeneration |
| ZHANG You-lei1△,HAN Qiu-cheng2△,LU Wen-feng1,FU Yong1,ZHU Nan1,YANG Ning1,YANG Guang-shun1* |
(1. Department of Hepatic Surgery Ⅴ, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China;
2. Department of Tumor Intervention, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201112, China
△Co-first authors.
* Corresponding author) |
| Abstract: |
| Objective To investigate the role of heparanase (HPSE) in regulating the liver regeneration after major hepatectomy in rats. Methods The HPSE small interfering RNA (siRNA) was designed and synthesized, and was transfected into the rats after 70% hepatectomy by in vivo-jetPEI-Gal vector. Then immunohistochemistry was performed to determine the expression of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). Western blotting analysis was performed to detect the expression of matrix metalloprotein (MMP)-2 and MMP-9 protein expression. Immunostaining for Ⅷ factor was done to observe the microvessels, and the microvessel density (MVD) was calculated. Results Compared with control group, the expressions of HGF, VEGF, MMP-2 and MMP-9 were significantly inhibited in HPSE siRNA group, and the MVD was significantly decreased (P<0.01). Conclusion HPSE may regulate liver regeneration via promoting HGF release in ECM, inducing hepatocyte proliferation, increasing VEGF expression to accelerate angiogenesis and upregulating the expression of MMP-2 and MMP-9. |
| Key words: heparanase small interfering RNA hepatectomy liver regeneration |
