지방간(脂肪肝) 형성과정에 관한 연구

Abstract

[한글]

[영문]

Accumulation of lipid in the parencymal cells is rather common and most frequently observed in the liver, heart, and kidneys. The fatty liver is found in diverse conditions, which include nutritional disturbances, infectious diseases, chronic anemia or ischemia, and injuries caused by various hepatotoxic agents.

Experimentally a fatty liver has been produced by carbon tetrachloride, phosphorus, ethanol, DDT, tannic acid, erotic acid, ethionine, etc. (Lombardi, 1966).

Regardless of causative agents, the accumulated lipid in talc liver cell is always neutral fat. Lombardi (1966) postulated that talc accumulated fat in the liver eells is due to either; 1) disturbance in talc utilization of triglycerides, 2) increased synthesis of triglycerides, 3) decreased utilization of triglycerides, or 4) synthesis of triglycerides outside of the endoplasmic reticulum.

It is customary to divide fat accumulation in the parenchymal calls into fatty infiltration and fatty degeneration. The former is due to the increased accumulation of fat without preceding on to cellular injury while in the latter the fat accumulates secondary to the prior cellular injury, The locus of fat synthesis in the liver cell is considered variously according to different investigators.

Kennedy and Lebninger (1948), Green (1954) reported that talc oxidation of fatty acids takes place in the mitochondria, while Baglio and Farber (1965) reported that it takes place in the rough endoplasmie reticulum, and palace (1955) reported the smooth endoplasmic reticulum is the site of fat formation.

The present investigation is aimed of studying trio mechanism, process and site of fat accumulation in the liver cells following the treatment of rats with different types of lipogenic factors.

Materials and Methods

Male albino rats weighing around 200 gms were used for the experiment and divided into the following group; normal control, high fat diet, carbon tetrachloride injected, ethionine injected, and talc acute anemic. The high fat diet contained 50% salad oil.

The carbon tetrachloride was injected subcutaneously in a single dose of 0.2 ml. per kg of the body weight, and ethionine was injected peritoneally in a single dose of 1g. per kg of the body weight. Acute anemia was produced by withdrawing approximately 4.0ml. of whole blood by cardiac puncture. The hematocrit value was determined in anemia and normal control group with the blood drawn immediately before the animals were killed.

Three animals from each group acre killed at 6, 12, 18, 24, 48, 72, 96 hours, 5, 7, and 10day intervals. Overall histologic alterations were observed by routine hematoxylin-eosin staining technic, and the degree and the pattern of fatty change were determined by the oil red-0 staining on frozen sections and thin sections taken from Epon block after osmic acid fixation counter stained with basic fuchsin. For the electronmicroscopic examinations, the tissue was fixed in 1% solution of csmic acid and dehydrated with graded alcohol. The sections were cut following Epon embeding in 400 to 500 A thickess with glass knife and stained with uranyl acetate and lead hydroxide.

Observation was made with Hitachi 11-E model electronmicroscope.

Results and Discussions

The hamatocrit dropped markedly following the cardiac puncture and gradually returned to normal value around the 7th day.

On light microscopic examinations, necrosis and ballooning of the liver cells were found in carbon tetrachloride treated group only, and mostly limited at the centrilobular zone. The animals in the remaining groups showed mild to moderate degree of vacuolization in the cytoplasm.

The accumulation of the lipid started from the periportal area in the animals treated with ethionine, high fat diet and cardiac puncture, where as it was first noted at the centrilobular zone in animals treated with carbon tetrachloride. The size of the fat globules was for and rather uniform in the animals fed on a high

fat diet and in the acute anemic group. The fat globules in ethionine treated animals were somewhat larger but uniform in size, while those of the carbon tetrachloride treated animals were irregular in size. The deposition of the fat apparently started from the peripheral portion of the liver cells and spread into perinuclear portion with increasing size.

Thc electronmicroscopic examinations revealed no notable alteration of the cytoplasmic organelles in high fat fed animals, and mild vacuolization with destruction of microvilli of bile cansliculi in the acute anemic group, while a made dilatation of the rough endoplasmic reticulum with detachment of ribosome,

decrease of free ribosome, and mild swelling of mitochondria were noted in animals treated with carbon tetrachloride or ethionine. The fat globules first appeared in the endoplasmic reticulum in all experimental groups, and their size increased from the peripheral to the perinuclear portion. In the animals treated with carbon tetrachloride or ethionine, numerous small electron dense granules appeared in the dilated rough endoplasmic reticulum preceding the appearance of fat globules, but no such granules were noted in high fat diet and acute anemic groups. Hyperplasia and aggregation of the smooth endoplasmic reticulum was noted only in carbon tetrachloride treated animals and did not seem to be related with the fatty change.

Summary: The accumulation of the fat in the liver cell started within the rough endoplasmic reticulum regardless of the causal factorsm initiated at the peripheral portion of the cisternae moving toward perinuclear portion with increasing size, and associated with carbon tetrachloride or ethionine.

But no such changes were noted in high fat fed and acutely anemic animals therefore a different mechanism, probably an increased synthesis of the fat in the former and a decreased utilization in the latter, must be acting.