Alloxan diabetes 및 膵管結紮이 cholesterol 食餌性 家兎動脈硬化症에 미치는 影響

Abstract

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[영문]

Dragstedt (1945) and Best (1948) drew attention on the significant role of the pancreas in atherogenesis through its endocrine and exocrine secretion.

Clawson and Bell (1949), Dodger (1950) and Bell (1952) found higher incidence of arteriosclerosis, peripheral gangrene, coronary diseases, and vascular diseases of the kidney among diabetics than non-diabetics based on the study of autopsy

materials. Bevans (1955)stated that arteriosclerosis in diabetics involves principally the arteries of medium and small size, and LeCompte (1955) stated that sclerotic process involves also capillaries and venules characterized by deposition of hyaline substance rich in polysaccharides in the wall. In 1958 Goldenberg et al.

found high incidence of non-atheromatous sclerosis of small branches of the coronary arteries in diabetic patients, and they interpreted the changes as the result of hypertension which is frequently associated with diabetes. Goldenberg et al,(1959) and Alex et al. (1959) reported that the non-atheromatous sclerosis

started with swelling of endothelial cells followed by proliferation of endothelial cells and deposition of colloidal-iron negative and PAS positive substance in the wall.

Rabinowitch (1935) speculated that increased serum cholesterol and triglycerides in diabetics enhance arteriosclerosis. However, reports on blood lipids in diabetics and particularly its relationship to the severity of atherosclerosis are still controversial. Man and Peters (1935) reported that they found hyperlipemia in 19 out of 79 diabetics, but there was also 9 cases of hypolipemia. Pomeranze and Kunkle (1950) observed increased serum total lipids in over 50% of 273 diabetic patients, and stated that increased serum total lipids and choleterol with decreased phospholipid. cholesterol ratio cause arteriosclerosis in diabetics.

However, Dewing et al. (1952) found that average serum cholesterol level is higher in diabetics than non-diabetics but its range was very wide and no definite correlation was noted between the level of serum cholesterol and severity of

atherosclerosis.

Not only the disturbance of internal secretion of the pancreas but also the disturbance of external secretion seems to influence on the atherogenesis through its role on lipids absorption (Chaikoff et al. 1952).

The present investigation is aimed to investigate the role of diabetes and ligation of pancreatic duct on experimental cholesterol induced atherosclerosis and to compare these with clinical observations.

Materials and Methods

Albino rabbits weighing around 1.8 kg were divided into 6 groups and treated as follows:

Group Ⅰ : Eight animals were used as alloxan diabetes control.

Group Ⅱ : Ten animals were given 1 gm of cholesterol daily for 10 weeks after induction of alloxan diabetes.

Group Ⅲ : Five animals were subjected to pancreatic duct ligation only.

Group Ⅳ : Fourteen animals were given 1 gm of cholesterol daily for 10 weeks after the ligation of pancreatic duct.

Group Ⅴ : Ten animals were given 1 gm of cholesterol daily for 10 weeks.

Group Ⅵ : Five animals were used as untreated normal control.

All animals were fed with 300 ems of bean-curd residue per animal per day.

Cholesterol was given mixed with a small amount of bean-curd residue early every morning at fasting state and full ingestion was confirmed. Alloxan diabetes was induced by the rapid intravenous injection of 100 mg of alloxan per kg and animals

which showed fasting blood sugar above 160 mg% at the 5 days after the alloxan injection were used for the experiments. The ligation of pancreatic duct was performed under sodium pentobarbital anesthesia .

Serum total cholesterol was determined at the 8th and 10th week in cholesterol fed groups and the 10th week in non-cholesterol fed groups, by the method of Pearson (1952).

All animals were killed by air embolization at end of the 10th week and necropsied. The aortas were examined gross]y and microscopically to evaluate the degree of atheroma formation. The heart was examined microscopically to observe coronary atherosclerosis. The kidney was also examined for atheromatous change. The liver was examined for the deposition of lipids, and the pancreas was examined for the histologic alterations of Langerhan's islets and exocrine glands. All tissue were embedded in paraffin after the fixation in 4% neutral formalin, and sectioned in 6μ. thickness. All sections were stained with hematoxylin and eosin.

Results and Summary

All animals fed with cholesterol skewed marked elevation of serum cholesterol without significant difference among the groups. The animals subjected to alloxan diabetes showed a tendency of somewhat lower serum total cholesterol and the

animals subjected to simple ligation of the pancreatic duct showed slightly higher serum total cholesterol level than normal untreated animals.

Macroscopic observations of the aortas showed greater amount of atheromatous changes in the animals fad with cholesterol after the induction of alloxan diabetes, particularly in the ascending portion. However, the degree of atheroma formation in the animals fed with cholesterol alone or after the ligation of pancreatic duct was not significant.

Microscopic findings of the atherosclerotic changes of the aortas showed also slightly increased degree of alheroma formation in the alloxan diabetes animals fed with cholesterol than other groups, but its difference was not as great as

macroscopic one.

Coronary arteries showed marked atheromatous changes involving mainly medium sized branches, and the most marked atheromatous change was observed in the animals fed with cholesterol after the pancreatic duct ligation. In this group, there was not only marked atheroma formation but also large degee of lipids depositon in the perivascular areolar tissue was noted. In animals fed with cholesterol after pancreatic duct ligation myocardial fibrosis was frequently observed.

The liver showed pronounced fatty changes iii all animals fed with cholesterol.

Nuclear vacuolization was occasionally noted in the alloxan diabetes control animal.

The pancreas showed complete disappearance of Langerhan's islets In the animals treated with alloxan. And the animals subjected to pancreatic duct ligation showed extensive fibrosis completely replacing acinar structure and leaving somewhat

proliferated and dilated ducts and scattered intact Langerhan's islets.

Blood vessels within the kidneys showed no notable atheromatous changes.

In summary, the data obtained by present investigation showed that alloxan diabetes enhance cholesterol induced atherosclerosis in the aorta, and that the ligation of the pancreatic duct enhanced coronary atherosclerosis. But the mechanism by which coronary and sortie atherosclerosis was enhanced in either group

is yet to be elucidated.