1992 Fiscal Year Final Research Report Summary
Hyperlipidemia and macrophages in the glomerular injury.
Project/Area Number |
03454216
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
内科学一般
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Research Institution | Tohoku University |
Principal Investigator |
SATO Hiroshi Tohoku University, School of Medicine, Assistant, 医学部附属病院, 助手 (60215829)
|
Co-Investigator(Kenkyū-buntansha) |
SEINO Jin 東北大学, 医学部附属病院, 助手 (20187826)
SAITO Takao 東北大学, 医学部附属病院, 講師 (10125552)
|
Project Period (FY) |
1991 – 1992
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Keywords | Focal glomerular sclerosis / Diabetic glomerulosclerosis / Aminonucleoside nephrosis / Hyperlipidemia / Macrophage / Foam cell / Triton WR1339 / Anti-hyperlipidemic agent |
Research Abstract |
Recently, intraglomerular macrophages and their transformation to foam cells are postulated to play an important role in the progression of glomerular sclerosis, as postulated in systemic atherosclerosis. In this study, we investigated the relationship between glomerular sclerosis and intraglomerular foam cells, on human subjects and on experimental models. At first, we documented the presence of intraglomerular macrophages and their foamy change in biopsy specimens of patients with focal glomerular sclerosis (FGS) and diabetic glomerulosclerosis. Next, we observed that intraglomerular macrophages and foam cells were significantly correlated with the degree of proteinuria and glomerular sclerosis in the experimental model of FGS with hyperlipidemia which was induced by administration of Triton WR1339 (TR) to uninephrectomized Sprague-Dawley rats with chronic aminonucleoside nephrosis. (TR-induced hyperlipidemia is characterized by an increase of triglyceride-rich lipoprotein.) In the next
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experiment, we examined the effect of two types of anti-hyperlipidemic agents, probucol and bezafibrate, on the TR-induced hyperlipidemic model. As a result, probucol, which has an anti-oxidative pharmacological effect, did not lower the serum level of total cholesterol and triglyceride, with no significant changes of proteinuria, intraglomerular foam cells, and the degree of glomerulosclerosis. On the other hand, bezafibrate significantly lowered serum level of triglyceride, and prevented both of the increase of proteinuria and the progression of glomerular sclerosis. From this result, abnormalities of triglyceride-rich lipoprotein are assumed to contribute to the progression of glomerular sclerosis. In conclusion, intraglomerular macrophages and their foamy change may play a key role in the progression of the glomerular sclerosis associated with hyperlipidemia. This process appears to be mediated by not only oxidative LDL modification but also triglyceride-rich lipoprotein derangement. Less
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Research Products
(10 results)