Glucocorticoids에 의한 간세포 투명팽대의 본질 : 조직화학적 및 전자현미경적 연구

Abstract

[한글]

[영문]

The presence of optically clear spaces in the cytoplasm of parenchymal cells of glucocorticoids treated liver sections are interpreted in various ways. Hill and Droke(1963) attributed the hepatocellular ballooning induced by parenterally administered cortisone to lipid accumulation, while kim et al.(1969) thought it was due to glycogen accumulation. But Gans and McEntee(1961) and Thompson et al.(1971) studied these ballooning cells with special histochemical methods and demonstrated that the material distending the cells was neither glycogen nor lipid, and they

speculated that the contents are probably water or diluted proteinic solutions. The role of cortisone and other corticosteroids in producing these alterations is still unknown and requires further study. The present studies are undertaken in an attempt to identify the nature of these ballooning cells induced by glucocorticoids by histochemical and electron microscopic studies.

Materials and Methods

Male albino rabbits weighing around 2.0kg. and male albino rats weighing around 200gms. were used for the experiment and divided into the following group, one normally controled and another glucocorticoids treated, which was in turn subdivided into cortisone acetate, prednisolone, and dexamethasone treated groups.

The cortisone acetate, prednisolone and dexamethasone were injected intramuscularly in a dose of 12.0mg., 3.0mg., and 0.6mg. per kg. of the body weight per day. The serum glucose value was determined by the method of Folin-Wu both in the normally control and glucocorticoids treated group were killed on the first, fifth and tenth day of the experiment and four rabbits of the control group were killed on the first, fifth and tenth day of the experiment and four rabbits of the glucocorticoids treated group on the 1st, 2nd, 3rd, 4th, 5th, 7th, and 10th day and two albino rats from each group on 1st, 5th and 10th day. Overall histologic

alterations were observed by routine hematoxylin-eosin staining technic, and PAS< D-PAS staining for mucopolysaccharides and glycogen, and Oil red-O staining for lipid demonstration were applied.

For the electron microscopic examination the tissue was fixed twice, first with 4% glutaraldehyde in phosphate buffer of pH 7.4 followed by 1% osmium tetraoxide in phosphate buffer of PH 7.4 for 2 hours, and embedded in Epon 812 following dehydration with graded alcohol. Sections were made with a glass knife of 400 to

500 A thickness and stained with uranyl acetate and lead hydroxide. Observation was made with Hitachi II-E model electron microscope.

Results and Discussion

The administraion of glucocorticoids to rabbits and albinoo rats resulted in a slight decrease in body weight, whereas the liver weight significantly increased in the animlas receiving glucocorticoids. But the water content of the liver remained

unchanged. Histological examination of rabbits receiving glucocorticoids revealed a marked ballooning and vesicular appearance of the hepatic cells in the midzonal and periportal areas of hepatic lobules. The maximal intensity of ballooning and

vesicular cytoplasmic changes in liver was observed in dexamethasone treated rabbits followed by prednisolone and cortisone acetate treated rabbits. Special stains and electron microscopic studies demonstrated that the material distending

the hepatic cells was glycogen only in the rabbits. But in the rats, the ballooning and vesicular changes of the hepatic cells were very mild in comparisons to the rabbits, and moreover special stains and electron microscopic studies demonstrated

that the nature fo the ballooning cells was the result of a combination of glycogen with lipid accumulation. The glycogen accumulation was accompanied by marked proliferation of SER, bur the proliferation of SER appeared to be the secondary to glycogen accumulation. After a maximal SER proliferation, further glycogen

accumulation was not demonstrable inspite of repeated glucocorticoids treatment.

Summary

The nature of hepatocellular ballooning induced by glucocorticoids treatment is due solely to glycogen accumulation in the rabbits, while it is due to a combination of glycogen with lipid accumulation in the rats, indicating that existed a species difference in the reaction to glucocorticoids.

The marked SER proliferation without glycogen accumulation appeared to be the result of glycogen accumulation rather than to be a cause, and more likely concerned with glycogenolysis.