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高麗人蔘이 動脈硬化症에 미치는 影響에 關한 實驗的硏究

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 (The) experimental studies on the influence of ginseng to the atherosclerosis in rabbits. 
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[영문] Since Anitshkow's observation in 1912 that feeding cholesterol dissolved in vegetable oil to rabbits resulted in the development of vascular lesions that were similar in many respects to those found in man, there have been numerous investigations to prove etiologic associations between hypercholesterolemia and atherosclerosis. Although the exact mechanism leading to the accumulation of lipid in the arterial wall and whether or not the lesions so induced in rabbits are truly analogous to those in man, remain unsettled, nevertheless feeding of cholesterol to rabbits has become one of the most reliable experimental methods to produce vascular lesions that chemically and histologically closely resemble those found in human atherosclerosis. Ginseng, known as the king of chinese drugs in oriental medicine, has been employed empirically in Asian countries for a large varieties of discorders as a panacea. However, modern scientific investigations failed to demonstrate its curious effects claimed by its advocators. Both the crude extract and its chemically pure components have been subjected to various pharmacological investigations, but the experimental results are not enough to proclaim the clinical value of this drug. On the studies of effects of Ginseng on the cardiovascular system, many have claimed that the Ginseng extract caused a marked fall in blood pressure. They have simply implied to a central depression for the cause without any conclusive evidences. The present investigation was undertaken to study the effects of Ginseng on the development of hypercholesterolemia and vascular lesions on rabbits fed cholesterol. MATERIAL AND METHODS The Ginseng (panax Ginseng C.A. Mey) proved by the Monopoly Department of Korea was used. The cholesterol powder (Purer cholesterin) was the preparation made by J.D.Riedel co., Berlin Germany. Fifteen albino male rabbits of similar age and weight (about 2kg) were divided into three groups after feeding a formular diet over one week as the following. Fifteen white male rabbits of similar age and weight (about 2kg) divided into three groups after feeding formular diet over one week duration as the following. Gorup Ⅰ (Control G.) consisted of 5 animals whose daily diet of formular schedule was supplemented with some pieces of vegetable. Group Ⅱ (Atherogenic G.) consisted of 5 animals whose daily formular diet was supplemented with some pieces of vegetable containing 0.5gm of cholesterol for 5 weeks, and then no cholesterol for 2 weeks. Group Ⅲ (experimental G.) consisted of 5 animals whose daily formular diet was supplemented with some pieces of vegetable containing 0.25gm each of cholesterol and Ginseng Powder for 3 weeks, 0.5gm of cholesterol and Ginseng powder for 5 weeks, and then no cholesterol and Ginseng for 2 weeks. All animals were weighed and blood samples were drawn from the ear vein at every two weeks interval for determinations of red cell count, hemoglobin, hematocrit, serum cholesterol, lipid phosphorus and phospholipid. After 10 weeks, the animals were sacrificed and the heart including coronary arteries, aorta and liver were removed and fixed immediately in 10% neutral formalin. The aorta was split longitudinally and examined so as to determine whether atheromatous lesions were present. Tissue sections from areas of aorta that grossly seemed to be the site of maximal atheromatosis, and sections from the heart and liver were made and stained with hematoxylin and eosin, and sudan Ⅳ. Results: A) General Findings No animal died before the completion of the experiment. There is no remarkable changes seen in general routine studies of body weight, red cell count and hematocrit. B) Biochemical Findings. In the rabbits that did not receive cholesterol, the level of serum cholesterol (47.6±1 mg% in 4 weeks, 52.7±7 mg% in 8 weeks, 54.9±7 mg% in 10 weeks) and serum phospholipid (82.7±1.1 mg% in 4 weeks, 82.6±2.8 mg% in 8 weeks, 94.3±8.1 mg% in 10 weeks) were not changed significantly throughout the course of the experiment. Most of the animals fed cholesterol had a marked increase in the concentration of serum cholesterol (204.0±22 mg% in 4 weeks, 546.6±58 mg% in 8 weeks, 405.1±88 mg% in 10 weeks) and serum phospholipid (140.8±22 mg% in 4 weeks, 258.0±52 mg% in 8 weeks, 244.4±43 mg% in 10 weeks). The group Ⅲ treated with Ginseng powder had lower average level in serum cholesterol (153.0±14 mg% in 4 weeks, 278.0±37 mg% in 8 weeks, 166.4±27 mg% in 10 weeks) and serum phospholipid (124.8±7.3 mg% in 4 weeks, 134.9±11 mg% in 8 weeks, 144.2±10 mg% in 10 weeks) throughout the study. C) Patholgical Findings Occasional atheroselerotic plaques characterized by hardness and roughness to the touch, tend to occur in the great vessels and this was more marked appreciably in one rabbit (No. 10) which was fed cholesterol and the formular diet. Characteristic atheromatous plaques were found under the microscope in the same rabbit. Although atheromatous plaques and fatty deposition in intima were found in the aorta and coronary arteries in 3 rabbits (No. 8,9,10) fed with the added cholesterol alone in their formular diet, no atheromatous change and fatty deposition in intima was seen in any animal fed with cholesterol and Ginseng in their formular diet. The liver of all the animals showed diffuse small granular yellow spots upon gross inspection. Fatty deposition in the liver was distintcly greater in the animals that received cholesterol added to their diet than in the control group. There was no definite differences on the fatty deposition in the liver in group Ⅱ and group Ⅲ. The greatest concentration of lipid were situated in the centrilobular regions. Discussion The level of serum cholesterol in the group Ⅱ, Ⅲ of rabbits was gradually elevaled by the diet containing cholesterol powder until 8th week. After that it was decreased by the diet without cholesterol powder before sacrification. Although the beta-lipoprotein fraction analysed by Gofman is closely related to the clinical atherosclerosis as the Kellner's infiltration theory, the determination of serum cholesterol or C/P ratio are still important to know the atherosclerotic change in aorta or coronary arteries. The difference 268mg% of serum total cholesterol level in group Ⅲ fed cholesterol and Ginseng powder from group Ⅱ is significant statistically (P<0.04) on the end of 8th week of this experiment, so that there is definitly some fact decreasing the hypercholesterolemia which is not yet explained well in the mechanism. It, however, may inhibit the esterification of cholesterol to absorb from the intestinal mucosa because 3 factors as the following are thought by lots of investigators. 1. Increasing the metabolic process or biliary excretion of cholesterol such as desiccated thyroid. 2. Inhibiting the absorption of such as unsaturated fatty acid, corn oil. 3. Enzymatic inhibiting of the endogenous synthesis of cholesterol in the liver such as Mer-29 and vanadium. But no investigator is explained well about the Niacin and Estrogen. Grossly and histologically no evidence of atherosclerotic change and sudanophilia was seen in the rabbits of group Ⅲ against the finding of typical atherosclerotic change and sudanophilia in the 3 rabbits of group Ⅱ, these findings are compatible with the lower serum cholesterol level and C/P ratio in the group Ⅲ than in the group Ⅱ. Although there was no well established explanation of the mechanism by which gineseng powder reduced hypercholesterolemia in animals, continued investigation of this therapy should however, be encouraged and expanded with the hope that additional insight might be gained concerning the mechanism of action of ginseng powder and its possible value in the prevention or treatment of atherosclerosis. Summary 15 male white rabbits of similar age and weight completed treatment as follows; Group Ⅰ (5 rabbits) received only a control diet of the formular diet; Group Ⅱ (5 rabbits) received the same diet plus 0.25-0.5 gm of cholesterol powder daily; Group Ⅲ (5 rabbits) received the control diet plus cholesterol powder and 0.25-0.5 gm of Ginseng powder daily. body weight, red cell count, hematocrit, serum cholesterol and serum phospholipid were determined every two weeks. At the end of tenth week, the animals were sacrificed and the aorta, heart including coronary arteries and liver were studied grossly and histologically. Neither ratheromatous vascular lesions nor increased values for serum cholesterol were noted in the control group. Hypercholesterolemia was present in both groups fed cholesterol but was less marked in the group that received also ginseng powder. Furthermore, in this latter group, the degree of aortic atheromatosis was less than in the group receiving cholesterol without ginseng powder. These findings justify the conclusion that oral doses of ginseng powder reduced the hypercholesterolemia and the aortic atheromatiosis produced in rabbits by the administration of cholesterol powder.
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