Role of "shear stress" in initiation of liver regeneration

“剪切应力”在肝再生启动中的作用

• 批准号: 12470262
• 负责人: IIMURO Yuji
• 金额: $ 8.96万
• 依托单位: HYOGO COLLEGE OF MEDICINE (2001)Kyoto University (2000)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470262/
• 关键词: liver regeneration; shear stress; partial hepatectomy; Racl; ischemia; reperfusion; 虚血再灌流; 肝虚血再灌流障害; 遺伝子導入

Change in portal blood flow after partial resection of the liver followed by increased "shear stress" has been proposed to play a critical role in initiation of liver regeneration. In the present study, we tried to investigate whether stretching mechanical stress resembling "shear stress" affect cell-proliferation of liver cells in vitro, and whether small GTPase Racl may participate in this process. Moreover, we analysed the effect of Racl-inactivation in the liver on regeneration-process after partial hepatectomy. To confirm that Racl activity was really inactivated in the liver with the method used in this study, we investigated another animal model. In a hepatic ischemia/reperfusion model, inactivation of Racl almost totally blocked hepatic injury after reperfusion. Therefore, we concluded that the method inactivating Racl activity used in this study t> was effective. After 70% partial hepatectomy, inactivation of Racl disturbed normal liver regeneration and activation of NFKB. From these results, we can speculate that Racl plays an important role in liver regeneration. Now we are investigating the effect of Racl-inactivation on cell proliferation of primary-cultured liver cells in vitro in a cell-stretching system, and trying to elucidate interaction among "shear stress", cell proliferation, and liver regeneration.

肝脏部分切除后门脉血流量的改变以及随后增加的“剪应力”被认为在启动肝脏再生中起着关键作用。在本研究中，我们试图研究类似于剪应力的拉伸机械应力是否影响体外培养的肝细胞的细胞增殖，以及小的GTP酶Rac1是否参与了这一过程。此外，我们还分析了肝组织中racl失活对肝部分切除后再生过程的影响。为了证实racl活性真的在肝脏中失活，我们研究了另一个动物模型。在肝脏缺血/再灌流模型中，Racl失活几乎完全阻断了再灌流后的肝损伤。因此，我们得出结论，本研究所采用的灭活racl活性的方法是有效的。70%肝部分切除后，racl的失活干扰了正常的肝再生和NFKB的激活。根据这些结果，我们可以推测Racl在肝再生中起着重要作用。现在，我们正在细胞拉伸系统中研究racl失活对体外培养的肝细胞增殖的影响，试图阐明剪切力、细胞增殖和肝再生之间的相互作用。

项目成果

Iimuro Yuji et al.: "Signal transduction through integrin is a main mechanism for hepatocyte proliferation by overexpression of matrix metalloproteinase-1 in the rat."Hepatology. 32・4. 321A-321A (2000)

Iimuro Yuji 等人：“通过整合素进行的信号转导是大鼠中基质金属蛋白酶-1 过度表达导致肝细胞增殖的主要机制。”Hepatology 321A-321A (2000)。

Yoshida M, Yamamoto N, Iimuro Y, et al.: "Suppression of Proliferative Cholangitis by E2F Decoy Oligodeoxynucleotide"Journal of Surgical Research. 102・2. 95-101 (2002)

吉田 M、山本 N、饭室 Y 等：“E2F 诱饵寡脱氧核苷酸对增殖性胆管炎的抑制”《外科研究杂志》102·2（2002 年）。

飯室勇二 他: "再生医療時代の幕開けを知る 肝再生-現状と展望"外科治療. 86・1. 9-14 (2002)

Yuji Iimuro 等：“了解再生医学时代的开始：肝脏再生 - 现状和前景” 86・1 (2002)。

Uyama N, Shimahara Y, Iimuro Y, et: "Regulation of Cultured Rat Hepatocyte Proliferation by Stellate Cells"Journal of Hepatology. (in press).

Uyama N、Shimahara Y、Iimuro Y 等：“星状细胞对培养大鼠肝细胞增殖的调节”肝脏病学杂志。

Oe S, Hirose T, Iimuro Y. et al.: "Continuous intravenous infusion of deleted form of hepatocyte growth factor attenuates hepatic ischemia-reperfusion injury in rats"Journal of Hepatology. 34・6. 832-839 (2001)

Oe S、Hirose T、Iimuro Y.等：“连续静脉输注缺失形式的肝细胞生长因子可减轻大鼠的肝脏缺血再灌注损伤”，《肝脏病学杂志》34・6（2001）。