ネフローゼ症候群の高脂血症の成因に関する研究　とくに末梢組織における脂肪代謝について

抄録

The pathogenesis of hyperlipemia observed in the nephrotic syndrome has been the subjects of many papers. It has been indicated that one factor contributing to this abnormality is a decreased rate of removal of serum lipid from the circulating blood. Moreover, the suggestion has been made that the release fat of from adipose tissue increases in the nephrotic syndrome. In the present study, attention was directed to the ability to remove circulating lipid by peripheral tissues and to the mobilization of fat from adipose tissue in the nephrotic syndrome of human beings (lipoid nephrosis and glomerulo nephritis) and of experimental nephrotic rats produced by subcutaneous injection of aminonucleoside (AN-rats). The results were as follows. 1. ¹³¹I-Triolein preparation was orally administered to analyze for whole blood ¹³¹I and lipid-bound ¹³¹I radioactivities. In the nephrotic patients, the maximum level of lipid-bound 1311 activity was higher than that of normal controls and the activity disappeared from the circulating blood of nephrotic patients at a slower rate, comparing with other groups. The ratio of lipid-bound ¹³¹I radioactivity to whole blood 1311 concentration was considerably higher in nephrotic patients than in normal controls and patients with chronic glomerulonephritis and minimum value was obtained in a group of patients withh cirrhosis of the liver. These results obtained in nephrotic patients may be presumptive evidence of, , a) increased synthesis of lipid in the liver, b) increased intry of synthesized lipid into the circulation, , . c) impaired ability to remove circulating lipid at the periphery, or d) a combination of these factors 2. The maximum level of heparin-induced plasma lipoprotein lipase (LPL) activity was lower is nephrotic patients than in normal controls. An inhibitor to LPL was observed in all plasma of nephrotic patients. Transitional changes with time of plasma LPL activity following the injection of heparin in patints with chronic glomerulonephritis were extremely characteristic. The maximum activity of plasma LPL was significantly correlated with such clinical parameters as serum total protein, albumin and cholesterol levels for diseased groups, but no correlation was found for nephrotic patients. The role of albumin and heparin in the pathogenesis of nephrotic hyperlipemia was discussed. 3. In vitro, the liberation of LPL from the epididymal fat pads and kidneys by heparin was redu-ced in AN-rats, although the release of LPL from the cardiac muscle showed no significant difference at 5% level in two groups. The impaired ability to remove circulating lipid by LPL mechanism in the nephrotic syndrome was ascertained in vivo and in vitro studies. The etiology of such reduced LPL activity in the nephrotic syndrome was a-lso discussed. 4. The lipase activity participating in the release of free fatty acids from adipose tissue was mar-kedly increased in the epididymal fat pads of AN-rats. This suggests the possibility that mobilization of fat from adipose tissue may be accelerated in the nephrotic syndrome, and also new concept that mobilization hyperlipemia is responsible for the pathogenesis of nephrotic hyperlipemia. However, this concept is inconsistent with the data reported hitherto and remains to be determined.