사람과 흰쥐 실험을 통한 인삼의 항혈전 효과에 관한 연구

Abstract

본 연구에서는 인삼의 효능을 알기 위해 동물 실험으로는 고지방 식이에 홍삼의 지용성 성분인 petroleum ether 추출물을 투여하여 항 혈전 및 간 기능에 미치는 영향을 살펴보았고, 인삼 장기복용자를 대상으로 식이섭취 실태와 혈청분석 및 혈장 응고인자 분석을 통해 항 혈전효과를 조사하였다. 동물실험은 1차, 2차로 나누어 시행하였고 15% corn oil(w/w)과 15% beef tallow(w/w) 식이로 3주간 사육한 후, 가장 효과를 나타내는 홍삼 PE 추출물의 양을 결정하기 위해 홍삼 PE 추출물을 0, 25, 200㎎/㎏ diet로 수준을 달리하여 3주간 투여후 혈소판 응집반응, thrombin time 및 혈청 지질분석을 통하여 15% corn oil diet에서 25㎎/㎏ diet가 항혈전 가능성에 가장 효과있다는 결론을 얻었다. 1차 실험을 토대로 2차 실험에서는 저지방식이에서도 홍삼투여가 고지방식이에서와 같은 효과를 주는가를, 또한 혈소판 응집억제 기전을 살펴보기 위하여 5% corn oil(w/w)과 15% corn oil(w/w) 식이에 홍삼 PE 추출물을 0, 25㎎/㎏ diet에 투여하여 혈소판 응집억제 기전, 혈장응고 시간, 혈청 지질 분석, 간 지질 분석을 통하여 다음과 같은 결과를 얻었다. Thrombin이나 collagen으로 유도된 혈소판 응집억제 기전에서 홍삼 PE 추출물은 cAMP 생성계보다는 cGMP 생성계를 통하여 15% corn oil + 홍삼 PE 추출물 25㎎군의 혈소판 응집을 강하게 억제하는 것으로 나타났다. 혈장응고 시간에서는 15% corn oil + 홍삼 PE 추출물 25㎎ 투여군에서 thrombin time이 연장되었고, prothrombin time과 activated partial thromboplastin time도 연장되어 혈소판 응집반응과 응고인자가 상호작용하여 혈전을 억제하는 결과를 얻었다. 혈청 지질 분석을 통하여 15% corn oil + 홍삼 PE 추출물 25㎎ 투여군에서 혈청 중성지방, total cholesterol, HDL-cholesterol, phospholipid가 감소되었고, LDL-cholesterol은 차이가 없었다. 또한 동맥경화지수가 대조군에 비해 저하하는 경향을 보여, 홍삼 PE 추출물이 동맥경화증에 효과가 있다고 여겨진다. 간의 지질함량에 대한 홍삼 PE 추출물의 영향은 15% corn oil + 25㎎ 투여군에서, 간의 총지질 함량이 감소되었고, 중성 지질이 감소되었다. 이것은 혈청지질의 변화를 반영하여 줄 뿐 아니라 간의 지질대사에 관여하며 간 기능개선 효과가능성을 나타내었다. 사람을 대상으로 한 연구에서 조사대상자들은 정상에 속하는 사람들이었다. 인사 장기복용자군은 일반인과 비슷한 식이섭취를 하고 있었던 것에 비하여 낮은 경향이었으며, HDL-cholesterol, LDL-cholesterol 함량은 차이가 없었다 또한 혈소판 수도 적고, 혈소판 응집력도 낮았고, APTT는 연장되어 있었다. 동물 및 홍삼 장기복용자 대상 연구에서 종합적으로 살펴볼 때, 홍삼은 항혈전 및 항동맥경화 효과와 더불어 간 지질 대사를 조절하여 간기능 개선효과도 갖는다고 결론지을 수 있다.;1. Animal study This study was designed to assess the effectiveness of petroleum ether extract supplements of Korea red ginseng in modifying serum lipids concentration, plasma clotting time, platelet aggregability and hepatic lipids concentration over two experiments. Rats were fed, for 3 weeks, high-fat (15% w/w) diets containing corn oil, beef tallow at the first experiments. After 3 weeks, petroleum ether extract of red ginseng has been administered to rats at the level of 0, 25 and 200㎎ per ㎏ of diet for 3 weeks. At the second experiments, rats were fed low (5% w/w) and high (15% w/w) diet containing corn oi for 3 weeks. After 3 weeks, petroleum ether extracts of red ginseng has been administered to rats at the level of 0 and 25㎎ per ㎏ of diet for 3 weeks. At 6 weeks of feeding, rats were killed and analyzed. The following results were obtained. Body weight changes were during 6 weeks feeding period showed that there were no significant difference in weights of rats fed high fat containing 15% corn oil and beef tallow. But there were increase in weights of rats fed 15% corn oil diet compared to 5% corn oil diet. Various weights such as liver, heart and kidney were not affected by the supplementation of red ginseng extracts and dietary fat for 6 weeks. But liver weights of 15% (w/w) corn oil diet were slightly heavier than those of 5% corn oil diet. Platelet aggregation to thrombin and collagen was strongly inhibited in 25㎎ supplements group containing 15% corn oil diet as compared with control group. Cyclic GMP production induced by collagen and thrombin was higher than cyclic AMP production in red ginseng extracts group. Thrombin clotting time was significantly elongated in 15㎎ supplements group containing 15% corn oil diet. Prothrombin time was not significantly different between 5% corn oil groups. But prothrombin time in 15% corn oil diet group was shortened to levels of 5% corn oil by supplementation of red ginseng. Activated partial thromboplastin time in 15% corn oil groups was elongated by supplementation of red ginseng. The serum concentration of lipid was affected by petroleum ether extracts of red ginseng. Triglyceride, LDL cholesterol and total cholesterol were reduced, whereas increasement in HDL cholesterol occurred in the group of red ginseng extracts containing 15% corn oil diet. The effect of red ginseng extracts on serum lipid concentration was different with containing dietary fat type and level of fat content. Total lipid and triglyceride concentration in liver was reduced in 25㎎ of red ginseng extracts group containing 15% corn oil diet. In conclusion, the effectiveness of supplements of red ginseng extracts was the highest in 25㎎ group of red ginseng extracts supplements. Inhibition of platelet aggregation, elevation of cyclic GMP, elongation of APTT and reduction of serum triglyceride, total cholesterol and phospholipid were usually considered antithrombotic. Supplementation of red ginseng extracts may result in benefical changes in pathological process leading to thrombotic occulsion. 2. Human study The participant in this study were 47 normal healthy volunteers (male 24, female 23) with an age range of 30-49 years and a median age of 41 years residing in Taejon. Based on the diet history, subjects were classed into one of three groups: omnivorous, vegetarians and ginseng consuming beyond 4 years. They were engaged in a variety of occupations and their socioeconomic status was middle class. Venous blood samples were taken for serum lipid profiling plasma clotting assay and platelet function. Dietary calorie intake were not significantly different in subjects. But fat intakes of vegetarians were lower than those of omnivorous and ginseng consumed group. Difference in fat intake affected serum lipid profiles, such that omnivorous male groups generally showed higher total cholesterol, LDL cholesterol, triglyceride and phospholipid than vegetarian male groups. But serum lipid profile values of ginseng consumed male groups, such as total cholesterol, triglyceride and phospholipid were lower than those of omnivorous male groups. The serom lipid profiles in the female subjects were not different, but total cholesterol, triglyceride and LDL-cholesterol levels in the group of ginseng consumed were low. Platelet cell count and platelet aggregation were low in the group of ginseng consumed. Ativated partial thromboplastin time was significantly elongated in the group of ginseng consumed. As mentioned above, it was found that consumption of ginseng could affect serum triglyceride, total cholesterol, phospholipid, plasma clotting factor and platelet aggregation. Therefore it is suggested that consumption of ginseng may have antithrombotic effect.