1992 Fiscal Year Final Research Report Summary
Experimental Study on the Functional Changes of Hepatic Reticuloendothelial System during Acute Liver Rejection.
| Project/Area Number |
02454301
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
NAKAMURA Satoshi Hamamatsu University School, Second Department of Surgery, Associate Professor., 医学部, 助教授 (00090027)
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| Co-Investigator(Kenkyū-buntansha) |
BABA Shozo Hamamatsu University School of Medicine, Second Department of Surgery, Chief Pro, 医学部, 教授 (40107818)
MURO Hiroyuki Hamamatsu University School of Medicine, Second Department of Pathology, Associa, 医学部, 助教授 (20107824)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Sinusoidal Endothelial Cell / Acute Liver Rejection / Fc Receptor / Hyaluronic Acid / Endothelin / Renal Dysfunction |
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| Research Abstract |
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
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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
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