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白鼠에 있어서 肝部分切除 및 甲狀腺機能低下가 脂質分布에 미치는 影響

The Effects of Partial Hepatectomy and Induced Hypothyroidism on the Tissue Lipid Distribution in Rats

중앙의학 1968년 15권 2호 p.123 ~ 143
김상진,
소속 상세정보
김상진 (  ) - 연세대학교 의과대학 병리학교실

Abstract


It has long since been recognized that the development of atherosclerosis is considered to be closely related to the degree and duration of hypercholesterolemia and. lipid metabolism is important in the pathogenesis of atherosclerosis.
Among the factors related to disturbance of lipid metabolism, there is abundant evidence in the literature that one of the main factors which influences the metabolism of lipids and cholesterol is the secretion of the endocrine glands of (Duell, 1955; Pincus, 1959). The role of the thyroid in controlling the level of plasma lipids and cholesterol is best established, and other endocrine glands such as pituitary, adrenals, gonads, and pancreas also effect the utilization of lipids and cholesterol (Rosenman et al, 1951 & 1952 b; Friedman et al., 1952 a & b; Stamler, 1953).
The mechanism by which the thyroid hormone affects cholesterol metabolism is not yet known, but there is evidence to suggest that cholesterol destruction is elevated in hyperthyroid rats (Byers et al., 1952c). Hence, it is assumed that the thyroid hormone acts on cholesterol metabolism via the liver (Rosenman et al., 1952b).
The liver is the organ where cholesterol synthesis predominantly occurs (Cornforth,. 1959), and is the main source for the plasma cholesterol (Friedman et al., 1951. a & b), Although biliary concentration of cholesterol is a reliable index of the rate of hepatic synthesis of this substance (Byers & Friedman, 1952 a & b), cholesterol synthesis may also occur elsewhere (Friedman et al., 1955; Beher et al. (1956).
This is strongly supported by the fact that the concentration of desmosterol in, several tissues may be higher than that observed in the liver and serum. Therefore, the levels of circulating cholesterol seems to be regulated by a dynamic interchange of cholesterol between blood and tissues stores (reversible pool), which would depend upon the amount of cholesterol available to the different areas of the body.
Induced hypercholesterolemia, when sufficiently prolonged, results in atherosclerosis in many animals. Dogs and especially rats are resistant; resistance in dogs, however, can be overcome feeding large amounts of cholesterol during induced hypothyroidism (Steiner & Kendall, 1946). The rat is generally considered to be very resistant to development of atherosclerosis. Although numerous attempts to produce atherosclerosis this species have been recorded, most have been completely unsuccessful (Horlick & Havel, 1948; Kendlla 1949; Marx et al., 1949; Altschul, 1950; Katz & Stamler, 1953), and the few reported instances of deposition of lipid in rat arteries have apparently had little resemblance to human atheros (Page & Brown, 1952; Bragden & Boyle, 1952 Wiissler et al., 1954; Fillios, et al., 1956).
The nature of this resistance to the development of experimental atherosclerosiss is unknown, and its elucidation on mechanisms is vital to further knowledge of the pathogenesis of the disease. One of the factors involved in the process of resistance may be hormonal (Steiner and Kendall, 1946)
Therefore, in rats a faw causes for natural resistance may be considered:1) endogenous destruction of the additional cholesterol; 2) excretion of the additional amount ingested viathe bile and the gastrointestinal tract;3) diminished endogenous synthesis of cholesterol in balance the additional amount ingested; 4) storage of the additional cholesterol outside the blood stream.
The majority of the studies, particularly in rats, have dealt mainly with the fluctuation of Plasma lipid levels and the production of atherosclerosis, but very little attention has been paid to lipid distribution with in various organs. Also it is recognized that the level of plasma lipid alone cannot adequately explain the varied features of the diseases resulting from disturbances in lipid metabolism. Therefore, study of the pattern of tissue lipid distribution in hypothyroid and partial hepatectomized, alone or combined, rats seems appropriate and important Moreover in order to consider the resistance of the production of atheromatous arterial lesions in rats. it is important to evaluate the factors which regulate lipid metabolism.
The purpose of this study is to characterize the patterns of tissue lipid distribution and define the nature of the morphological changes in various organs in rats, after prolonged administration of high concentration of cholesterol. At the same time, the effect of Tapazole (antithyroid) and of partial hepatectomy was evaluated as to mechanism (s) involved in their action on tissue lipid alterations.

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