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Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy 被引量:32

Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy
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摘要 AIM: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy. METHODS: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and e-smooth muscle actin (α-SNA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal bUiary drainage in BO rats or sham-operated rats. RESULTS: Hepatic TGF-β1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-β1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs (desmin-positive cells) and activated HSCs (α-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-β1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats. CONCLUSION: BO induces HSCs proliferation and activation, leading to up-regulation of TGF-β1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice. 瞄准:在部分肝切除术以后在肝新生上学习妨碍的黄疸的效果。方法: Hepatocyte 生长因素( HGF ),它的受体, 遇见c ,脉管的内皮生长因素( VEGF )和转变生长在肝织物和孤立的肝细胞的 factor-beta1 ( TGF-beta1 ) mRNA 表示被量的反向抄写的聚合酶链反应( RT-PCR )用 LightCycler 在胆汁的阻塞( BO )以后调查。为 desmin 和 alpha 光滑的肌肉肌动朊(alpha-SMA ) 染色的 Immunohistochemical 也被学习。标记的原子抗原(PCNA ) 索引的再生肝重量和增殖的房间,和生长因素表示然后与伴随物在 70% 肝切除术以后被评估在 BO 老鼠或假冒操作老鼠的内部胆汁的排水。结果:肝的 TGF-beta1 mRNA 层次显著地在 BO 以后增加了 14 天,并且进一步与胆汁郁积的持续时间增加了。同时, HGF 和 VEGF 趋于增加,但是不是重要的。在房间孤立, TGF-beta1 mRNA 主要在肝的星形的房间(HSC ) 被发现部分。Immunohistochemical 研究揭示了 HSC (desmin 积极的房间) 的一个增加的数字并且在 BO 以后在门区域激活 HSC (alpha-SMA-positive 房间) 。在一个肝切除术模型,肝新生在 BO 老鼠被推迟,作为与假冒操作老鼠相比。在肝切除术,和更早的 HGF mRNA 山峰沉醉于 BO 老鼠以后, TGF-beta1 mRNA 是显著地起来调整的直到 48 h。结论:BO 导致 HSC 增长和激活,导致 TGF-beta1 mRNA 的起来规定和在肝的 HGF mRNA 的抑制。这些改变的表示模式可以强烈与妨碍的黄疸在肝切除术以后涉及推迟的肝新生。
出处 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第13期2053-2059,共7页 世界胃肠病学杂志(英文版)
关键词 Biliary obstruction Liver regeneration Hepatocyte growth factor Transforming growth factor-β Hepatic stellate cells HEPATECTOMY 生长因子 细胞因子 胆管阻塞 肝脏切除术
作者简介 Correspondence to: Dr. Hiroaki Shimizu, Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-0856, Japan. h-shimizu@umin.ac.jp Telephone: +81-43-2262103 Fax: +81-43-2262552
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  • 1Shinji Mitsue,Masahiro Hamanoue,Gen Tanabe,Yoshito Ogura,Shinrou Yoshidome,Takashi Aikou,Toshikazu Nakamura.Expression of HGF and TGF-β1 mRNA after partial hepatectomy in rats with liver cirrhosis[J].Surgery Today.1995(3)

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