Experimental Study on the Functional Changes of Hepatic Reticuloendothelial System during Acute Liver Rejection.

急性肝排斥反应期间肝网状内皮系统功能变化的实验研究。

• 批准号: 02454301
• 负责人: NAKAMURA Satoshi
• 金额: $ 1.28万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454301/
• 关键词: Sinusoidal Endothelial Cell; Acute Liver Rejection; Fc Receptor; Hyaluronic Acid; Endothelin; Renal Dysfunction; enclothelin; 肝移植; 急性拒絶反応; Fcリセプタ-; ヒアルロン酸; 拒絶反応; 網内系機能

Hepatic reticuloendothelial system (RES) plays an key role in hepatic blood clearance and much attention has been focused on the changes of RES function in various liver diseases. However there has been so far no functional analysis of RES in acute liver rejection. The aim of this study is to identify the changes of RES, especially sinusoidal endothelial cells (SECs), in acute liver rejection.We performed orthotopic rat liver transplantation as follows: Lewis rats grafted with DA rat livers as rejectors, and Lewis rats with Lewis rat livers as controls. Our study was divided into two experiments as below.(Experiment 1) Functional abnormalities of sinusoidal endothelial cells in rats with acute liver rejection. As indicators of SECs function, Fc receptor (FcR) activity of SECs and serum level of hyaluronic acid (sHA) were determined. In rejectors, FcR activity of SECs was significantly declined and the sHA level was elevated than in controls after postoperative day 3, which preceded the … More significant change of serum bilirubin levels. This result suggest that impairment of the SECs function develops at an early phase of acute liver rejection than do other abnormality of traditional indicator.(Experiment 2) Role of endothelin in the pathophysiology of renal impairment during acute liver rejection. Endothelin (ET) is a strong vasoconstrictor peptide produced by endothelial cells, and much attention has been focused on the pathophysiological role of ET in various conditions associated with renal dysfunction. Based on the result of experiment 1, we determined the relationship between the serum ET level and renal function during acute liver rejection, where vascular endothelialitis is a prominent histological feature. After postoperative day 5, the serum ET level in rejectors was significantly elevated in association with the significant decrease of the endogenous creatinine clearance (Ccr) and renal hemodynamic indicators. In addition, the increase in serum ET level was well correlated with the decrease in Ccr and renal hemodynamic parameters. These results suggest an important role of ET in the pathophysiology of renal impairment during acute liver rejection.In conclusion, the impairment of SECs function develops in acute liver rejection, which is considered to play a role in renal dysfunction during rejection where the pathogenesis depends upon the elevation of serum ET. Less

肝网状内皮系统(Res)在肝脏血液清除中起着关键作用，其功能在各种肝病中的变化已引起人们的广泛关注。然而，到目前为止，还没有Res在急性肝排斥反应中的功能分析。本研究旨在探讨急性肝排斥反应中肝细胞尤其是肝窦内皮细胞(SECs)的变化。我们进行了如下大鼠原位肝移植：Lewis大鼠移植DA大鼠肝脏作为排斥反应，Lewis大鼠移植Lewis大鼠肝脏作为对照。本研究分为两个实验：(实验一)急性肝排斥大鼠肝窦内皮细胞功能异常。测定SECs Fc受体(FCR)活性和血清透明质酸(SHA)水平作为SECs功能的指标。排斥组术后第3天…前SECs的FcR活性显著低于对照组，SHA水平高于对照组。血清胆红素水平变化更为显著。这一结果表明，与传统指标的其他异常相比，SECS功能受损发生在急性肝排斥反应的早期。(实验2)内皮素在急性肝排斥反应肾损害病理生理学中的作用。内皮素(ET)是一种由内皮细胞产生的强缩血管活性多肽，其在肾功能不全相关疾病中的病理生理作用已引起人们的广泛关注。根据实验1的结果，我们确定了急性肝排斥时血清ET水平与肾功能的关系，其中血管内皮炎是一个突出的组织学特征。术后第5天，排斥组血清ET水平显著升高，内生肌酐清除率(Ccr)和肾血流动力学指标显著下降。此外，血清ET水平的升高与Ccr和肾血流动力学参数的降低密切相关。这些结果提示ET在急性肝排斥时肾损害的病理生理学中起重要作用。结论：急性肝排斥时SECS功能受损，这被认为在排斥时肾功能障碍中发挥作用，其发病机制依赖于血清ET的升高。较少

项目成果

Nishiyama R, Nakamura S, Suzuki S, et al: "Platelet activating factor (PAF) in hepatic ischemia/reperfusion injury. -Effects of a PAF antagonist combined with a prostaglandin I_2 analogue-" Transplantation.

Nishiyama R、Nakamura S、Suzuki S 等人：“肝缺血/再灌注损伤中的血小板激活因子 (PAF)。-PAF 拮抗剂与前列腺素 I_2 类似物联合的效果-”移植。

Suzuki.S, Nakamura.S, KoizuminT, et al.: "The beneficial effect of a prostoglanain IEB2EB analogue on ischemic rat liver" Transplantation. 52. 979-983 (1991)

Suzuki.S、Nakamura.S、KoizuminT 等人：“前列腺素 IEB2EB 类似物对缺血性大鼠肝脏的有益作用”移植。

Nishiyama R,Nakamura S,Suzuki S,et al.: "Platelet-activating facto(PAF)in hpatic isclemia/reperfasoir Cnjury.-Effects of a PAF antogonist conbined with a prostaglonelin I_2Onalogue-." Transplantation.

Nishiyama R、Nakamura S、Suzuki S 等人：“肝缺血/reperfasoir Cnjury 中的血小板激活因子 (PAF)。-PAF 拮抗剂与前列腺素 I_2Onalogue 联合使用的效果-”。

Shohachi Suzuki.,Satoshi Nakamura.,Hiroyuki Muro et al: "The Beneficial effect of a Prostaglandin Iz analog on ischemic rat liver" TRANSPLANTATION. 52. 978-983 (1991)

Shohachi Suzuki.、Satoshi Nakamura.、Hiroyuki Muro 等人：“前列腺素 Iz 类似物对缺血性大鼠肝脏的有益作用”移植。

Nakamura S,Nishiyama R,Serizawa A,et al.: "Hepatic release of enaothelin-1 after warm ischemia-reperfusion injury." Surgery.

Nakamura S、Nishiyama R、Serizawa A 等人：“热缺血再灌注损伤后肝脏释放 enaothelin-1。”