Pathophysiology of the liver and development of a novel therapeutics based on morphological and functional study on hepatic sinusoidal
肝脏的病理生理学以及基于肝窦形态和功能研究的新型疗法的开发
基本信息
- 批准号:08457322
- 负责人:
- 金额:$ 4.93万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:1996
- 资助国家:日本
- 起止时间:1996 至 1997
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
1.Study on protection of hepatic damage during cold preservation. In our previous studies, we clarified Kupffer cell activation during cold preservation, inducing an injury of simusoidal endothelial cells(SEc) through tissue toxic mediators. In the present study, we attempted to prove an alternative mechanism of SEC injury, that is apoptosis, because SEC damage appeared at earlier peroid than Kupffer cell activation. Consequently, we made clear the apoptotic change of SEC with high frequency during cold preservation by electron microscopy and Tunel method. Furthermore, we found that vascular endothelial growth factor(VEGF) contributed to the suppresssion of apoptosis. In addition, we studied an ultrastructural alteration of cold-preserved fatty liver based on the evidence that a datty liver is one of main risk factors for primary nonfunctioning graft. We found that SEC damage proceeded prior to cold preservation and then accerelated during the preservation. The morphological changes we … More re increase in bleb formation, expansion of gap and string-like appearance in SEC.With regard to hepatocytes, size of fat droplets was enlarged with the duration of cold preservation, and then occupied cytoplasma. This change caused the oppression of sunusoid and narrowness of sinusoidal caliber. These findings suggested that a causative mechanism of graft failure in the transplantation of fatty liver may be microcirculatory disturbance of hepatic sinusoid. 2.Discovery of Na-Ca exchanger in Ito cells. Ito cells are adhered to outlayr of sinusoid, and is considered to be participated in the regulation of sinusoidal circulation by the own contraction. This contraction is regulated by the cytoplasmic Ca ion concentration. In the present study, we discovered first Na-Ca exchanger in Ito cells and further found that the expression of the mRNA and the protein was closely correlated with the activation of Ito cells and liver fibrosis. 3.Significance of nitric oxide(NO) in portal hemodynamics of liver cirrhosis. More recently, evidence has accumulated indicating that NO is closely related to the hyperdynamic change seen in the liver cirrhosis. However, the role of NO in this pathology is still remained to be resolved. In the present study we demonstrated that NO plays a significant role in portal hypertensive hemodynamics in CCl_4-induced liver cirrhosis, and that NO is a useful indicator for the evaluation of portal hypertension. Furthermore, the increased serum levels of NO were found to be derived at least in part from the increased expression of iNOSmRNA in the liver, spleen and lung. Less
1.低温保存过程中肝损伤保护的研究。在我们之前的研究中,我们阐明了Kupffer细胞在冷保存过程中的激活,通过组织毒性介质诱导类血管内皮细胞(SEc)损伤。在本研究中,我们试图证明SEC损伤的另一种机制,即细胞凋亡,因为SEC损伤出现的时间比Kupffer细胞活化的时间早。因此,我们通过电镜和Tunel法明确了SEC在低温保存过程中高频凋亡的变化。此外,我们发现血管内皮生长因子(VEGF)有助于抑制细胞凋亡。此外,我们研究了冷保存脂肪肝的超微结构改变,因为肝脏损伤是原发性移植物无功能的主要危险因素之一。我们发现SEC损伤在冷保存之前就开始了,然后在保存期间加速了。肝细胞随着低温保存时间的延长,脂肪滴的大小逐渐增大,并逐渐占据细胞质。这种变化造成了正弦波的压迫和正弦波口径的变窄。这些结果提示脂肪肝移植失败的机制可能是肝窦微循环障碍。2.Ito细胞中Na-Ca交换器的发现。Ito细胞粘附在窦外膜上,通过自身收缩参与了窦循环的调节。这种收缩受细胞质钙离子浓度的调节。在本研究中,我们首次在Ito细胞中发现了Na-Ca交换器,并进一步发现mRNA和蛋白的表达与Ito细胞的活化和肝纤维化密切相关。3.一氧化氮在肝硬化门静脉血流动力学中的意义。最近,越来越多的证据表明NO与肝硬化的高动力变化密切相关。然而,NO在该病理中的作用仍有待解决。在本研究中,我们证明NO在ccl_4诱导的肝硬化门静脉高压血流动力学中起着重要作用,并且NO是评估门静脉高压的有用指标。此外,发现血清NO水平的升高至少部分源于肝、脾和肺中iNOSmRNA表达的增加。少
项目成果
期刊论文数量(24)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Shin-ichi Fujita: "The preventive effects of OK342 on endotoxing-induced liver injury" Surg.Today. 26. 27-35 (1996)
Shin-ichi Fujita:“OK342 对内毒素引起的肝损伤的预防作用”Surg.Today。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Masaki Mizumoto, Shigeki Arii: "NO as an indicator of portal hemodynamics and the role of NOS in increased NO production in CCl_4-induced liver cirrhosis" J.Surg.Res.70. 124-133 (1997)
Masaki Mizumoto、Shigeki Arii:“NO 作为门静脉血流动力学指标以及 NOS 在 CCl_4 诱导的肝硬化中 NO 产生增加中的作用”J.Surg.Res.70。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Masaki Mizumoto: "No as an indicator of portal hemodynamics and the role of NOS in increased NO production in ccl_4-induced liver cirrhosis" J.Surg.Res.70. 124-133 (1997)
Masaki Mizumoto:“No 作为门静脉血流动力学指标以及 NOS 在 ccl_4 诱导的肝硬化中 NO 产生增加中的作用”J.Surg.Res.70。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Mototaka Niwano, Shigeki Arii: "Amelioration of sinusoidal endo-thelial cell damage by Kupffer cell blockade during cold preservation of rat liver" J.Surg.Res.72. 36-48 (1997)
Mototaka Niwano、Shigeki Arii:“大鼠肝脏冷藏期间通过库普弗细胞阻断改善正弦内皮细胞损伤”J.Surg.Res.72。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Masaki Mizumoto: "NO AS AN INDICATOR OF PORTAL HEMODYNAMICS AND THE ROLE OF INOS IN INCREASED NO PRODUCTION IN CCL4-INDUCED LIVER-CIRRHOSIS" J.Surg.Res.70. 124-133 (1997)
Masaki Mizumoto:“NO 作为门脉血流动力学指标以及 INOS 在 CCL4 诱导的肝硬化中 NO 产生增加中的作用”J.Surg.Res.70。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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- 通讯作者:
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ARII Shigeki其他文献
ARII Shigeki的其他文献
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{{ truncateString('ARII Shigeki', 18)}}的其他基金
Study on the molecular diagnosis of metastasis and recurrence and molecular targeted therapy for intractable hepato-pancreatic cancer
难治性肝胰腺癌转移复发的分子诊断及分子靶向治疗研究
- 批准号:
20249061 - 财政年份:2008
- 资助金额:
$ 4.93万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Multidisciplinary research for molecular mechanism of cancer progression and development of diagnostic and therapeutic tool
癌症进展分子机制的多学科研究及诊断和治疗工具的开发
- 批准号:
18209043 - 财政年份:2006
- 资助金额:
$ 4.93万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Development of molecular- targeting therapy and prediction of mode of recurrence by analysis of molecular mechanism of invasion and metastasis of hepatocellular carcinoma
肝细胞癌侵袭转移分子机制分析分子靶向治疗发展及复发模式预测
- 批准号:
16390375 - 财政年份:2004
- 资助金额:
$ 4.93万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Order-made medicine for cancer in the viewpoint of angiogenesis
从血管生成的角度进行癌症定制治疗
- 批准号:
14370379 - 财政年份:2002
- 资助金额:
$ 4.93万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study on the improvement of liver injury by controlling sinusoidal cells and spleen
控制肝窦细胞和脾脏改善肝损伤的研究
- 批准号:
12470257 - 财政年份:2000
- 资助金额:
$ 4.93万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of novel gene therapies in the field of liver surgery
肝脏外科领域新型基因疗法的开发
- 批准号:
09557104 - 财政年份:1997
- 资助金额:
$ 4.93万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Implication of hepatic sinusoidal cells in pathophysiology of the liver diseases and development of novel therapeutic strategies
肝窦细胞在肝脏疾病病理生理学中的意义及新治疗策略的开发
- 批准号:
06454383 - 财政年份:1994
- 资助金额:
$ 4.93万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
相似海外基金
A study of regulation of Kupffer-cell activation by intracellular lipid metabolism and its involvement in the pathogenesis of liver fibrosis.
细胞内脂质代谢调节库普弗细胞活化及其参与肝纤维化发病机制的研究。
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从凋亡细胞感知到先天记忆反应:库普弗细胞功能的新方面 (P02*)
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396771936 - 财政年份:2018
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Collaborative Research Centres
Investigation of the role of FABP7 in the regulation of Kupffer cell activation through the intracellular lipid metabolism
研究 FABP7 通过细胞内脂质代谢调节库普弗细胞活化的作用
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18K14998 - 财政年份:2018
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$ 4.93万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Exercise practice improves Kupffer cell function and reduces a risk of steatohepatitis and hepatic carcinogenesis.
锻炼练习可以改善库普弗细胞功能,降低脂肪性肝炎和肝癌发生的风险。
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17H02174 - 财政年份:2017
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Grant-in-Aid for Scientific Research (B)
Kupffer cell dysfunction in liver cirrhosis leads to uncontrolled infection
肝硬化中的库普弗细胞功能障碍导致不受控制的感染
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386680738 - 财政年份:2017
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Research Fellowships
Kupffer Cell Necroptosis and Homeostatic Function in Liver Immune Responses against Ischemia Reperfusion Injury
库普弗细胞坏死性凋亡和肝脏缺血再灌注损伤免疫反应中的稳态功能
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9167747 - 财政年份:2016
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Role of Kupffer Cell and NK Cell Interactions in Hepatitis C Virus Infektion
库普弗细胞和 NK 细胞相互作用在丙型肝炎病毒感染中的作用
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281237536 - 财政年份:2015
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Research Grants
Development of Medaka Model for Analysis of Angiogenesis and Kupffer cell
用于分析血管生成和库普弗细胞的青鳉模型的开发
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25670370 - 财政年份:2013
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Kupffer cell activation and hepatic injury after ethanol and burn
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Kupffer cell activation and hepatic injury after ethanol and burn
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