Browse > Article

Effects of Concurrent Administration of Sopunghwalhyeol-tang and Clopidogrel on Atherosclerosis in the $ApoE^{(-/-)}$ Mouse  

Lee, Beom-Joon (Dept. of Oriental Internal Medicine, Kangnam Korean Hospital, Kyunghee university)
Oh, Sae-Choon (East-west Medicine, The graduate School of East-West Medical Science, Kyunghee university)
Kim, Young-Chan (East-west Medicine, The graduate School of East-West Medical Science, Kyunghee university)
Lee, Jeong-Sook (East-west Medicine, The graduate School of East-West Medical Science, Kyunghee university)
Kang, Deok-Hee (East-west Medicine, The graduate School of East-West Medical Science, Kyunghee university)
Lee, Woo-Kyoung (East-west Medicine, The graduate School of East-West Medical Science, Kyunghee university)
Lee, Young-Il (East-west Medicine, The graduate School of East-West Medical Science, Kyunghee university)
Lew, Jae-Hwan (East-west Medicine, The graduate School of East-West Medical Science, Kyunghee university)
Publication Information
The Journal of Korean Medicine / v.31, no.5, 2010 , pp. 124-135 More about this Journal
Abstract
Background and Objective: Atherosclerosis is a diffuse, systemic disease that affects the coronary, cerebral, and peripheral arterial trees. Clopidogrel is widely used antiplatelet agent and its efficacy has been proven in cardiac and extracardiac vascular diseases, but it has several side effects. Therefore we investigated whether Sopunghwalhyeoltang, which is widely used for treating the blood stasis syndrome in traditional medicine, could decrease the side effect of antiplatelets and have a synergic effect. Methods & Materials: Male $ApoE^{(-/-)}$ mice were randomly divided into three different experimental groups, non-treated group (Control group), clopidogrel-treated group (CP group) and clopidogrel with Sopunghwalhyeol-tang treated group (CPS group). The control group was fed with only an atherogenic diet, the CP group an atherogenic diet plus clopidogrel 25mg/kg and the CPS group an atherogenic diet plus clopidogrel 25mg/kg with Sopunghwalhyeol-tang 100 mg/kg. We investigated plasma lipids with liver function test, and performed a histological investigation of liver and abdominal aorta. Results: 1. Photomicrographs of liver and abdominal aorta tissue showed lower histological injury and lipid accumulation in the CP and CPS groups than those in the Control group. 2. In the CPS group, plasma triglyceride level was significantly lower than in the Control and CP groups. 3. In the CPS group, the plasma aspartate aminotransferase (AST) level was significantly lower than in the CP group. Conclusions: The above results shows that a combined treatment of Sopunghwalhyeol-tang and clopidogrel have a synergic effect through inhibiting vessel injury and decrease the side effects of clopidogrel alone.
Keywords
atherosclerosis; hyperlipidemia; Sopunghwalhyeol-tang; clopidogrel; $ApoE^{(-/-)}$ mouse;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Wong ND, Cupples LA, Ostfeld AM, Levy D, Dannel WB. Risk factors for long-term coronary prognosis after initial myocardial infarction. The Framingham Study. Am J Epidemiol. 1989;(130) :469-80.
2 Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007; 115:450-458.   DOI   ScienceOn
3 Rodondi N, Bauer DC. Assessing the risk benefit profile before recommending aspirin for the primary prevention of cardiovascular events. American J Med. 2004;117:528-30.   DOI   ScienceOn
4 김태영. 加味疎風活血湯이 류마토이드 關節炎에 미치는 實驗的硏究. 대전: 대전대학교대학원; 2006.
5 Moon YH, Kim GW, Um KJ. Pharmacological studies on the Sopunghwalhul-Tang -on Analgesic, Antiinflammation and Hypotension. Kor J Pharmacogn. 1991;22(4):240-5.
6 곽중문. 疎風活血湯加味가 류마토이드 關節炎 患者에서 分離한 synoviocytes에 對한 免疫反應 과 collagen으로 誘發된 생쥐의 關節炎抑制에 關한 硏究. 대전: 대전대학교대학원; 2002.
7 양동원. 加味疎風活血湯이 炎症誘發cytokine과 MRL/MpJ-lpr 생쥐의 關節炎抑制에 關한 硏究. 대전: 대전대학교대학원; 2003.
8 남영. 歷節風에 응용되는 疎風活血湯의 消炎, 鎭痛, 解熱효과에 관한연구. 서울: 경희대학교대학 원; 1981.
9 방혜정, 강윤호. 고지혈증의 처방에 관한 문헌적 고찰. 동서의학. 1996;21(2):70-81.
10 沈金鰲. 沈氏尊生書. 臺北: 自由出版社. 1980: 309-17.
11 송언석. 加味疎風活血湯水鍼이 Adjuvant 關節炎에 미치는 影響. 서울: 경희대학교대학원; 1990.
12 김정진. 濃度에 따른 加味疎風活血湯水鍼이 흰쥐의 Adjuvant 關節炎에 미치는 影響. 서울: 경희 대학교대학원; 1990.
13 안선준. 鍼灸刺戟및 疎風活血湯加味方 投與가 류마티스性 關節炎 患者의 血液에 미치는 影響. 익산: 원광대학교대학원; 1994.
14 Fauci AS, Braunwald E, Isselbacher KJ, Longo DL. Harrison's principles of intermal medicine 14th ed. McGraw-Hill Hesgpth Professions Division: USA; 1994,2139.
15 Gum PA, Kottke MK, Poggio ED, Gurm H, Welsh PA, Brooks L, et al. Profile and prevalence of aspirin resistance patients with cardiovascular disease. American J Cardiol. 2001;88:230-5.   DOI   ScienceOn
16 Gwak HS, Chun IK. Performulation study of aspalatone. a new antithrombotic agent. J Appl Pharmacol. 2000;8:332-7.
17 정우열, 안규석. 韓方臨床病理學. 서울:永林社. 1998:545.
18 Cho HK, Jang YS. Small Dense LDL and Atherosclerosis. J Korean Soc Lipidol Atheroscler. 2003;13(2):333-8.
19 김치정. 동맥경화증의 정의와 역사. 서울:의약정보. 1994;12월호:22-8.
20 Arbige M, Pitcher WH. Industrial enzymology. a look towards the future. Trends Biotechnol.1989;7:330-35.   DOI   ScienceOn
21 대한병리학회. 병리학. 서울:고문사. 1990;480.
22 Beltran RM, Marquez SE, Sanchez MD, Romero GM. Hepatotoxicity induced by clopidogrel. Journal of Hepatology. 2004;40:559-565.   DOI   ScienceOn
23 전국한의과대학 심계내과학교실. 心系內科學(심혈관계, 신경계). 서울:군자출판사. 2006:169-78.
24 Christeopher KG, Joseph IW. Atherosclerosis: The road ahead. Cell. 2001;104:503-16.   DOI   ScienceOn
25 Han KH. Is Triglyceride Atherogenic? Journal of Korean Endocrine Society. 2009;24(3):151-5.   DOI   ScienceOn
26 Reddick RL, Zhang SH, Maeda N. Atherosclerosis in mice lacking ApoE. Evaluation of lesional development and progression. Arterioscler Thromb Vasc Biol. 1994;14:141-7.   DOI
27 신현호. 고지혈증의 약물요법. 한국지질학회 제1차 동맥경화와 고지혈증 Workshop. 1994;41-9.
28 Roselaar SE, Kakkanathu PX, Daugherty A. Lymphocyte populations in atherosclerotic lesion of ApoE-/- and LDL receptor-/- mice. Decreasing density with disease progression. Arterioscler Thromb Vasc Biol. 1996;16:1013-8.   DOI   ScienceOn
29 Wiper A, Schmitt M, Roberts DH. Clopidogrelinduced hepatotoxicity. Journal of Postgraduate Medicine. 2008:54(2);152.   DOI   ScienceOn
30 Zhou X, Stemme S, Hansson GK. Evidence for a local immune response in atherosclersis. CD4+ T cells infiltrate lesion of apolipoprotein E deficient mice. Am J Pathol. 1996;149:359-66.
31 Beckman JS, Beckman YW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA. 1990;(4) :1620-4.
32 Plump AS, Smith JD, Hayek T, Aalto-Setala K, Walsh A, Verstuyft JG, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E deficient mice created by homologous recombination in ES cells. Cell. 1992;71:343-53.   DOI   ScienceOn
33 Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb Vasc Biol. 1994;14:133-140.   DOI
34 易法銀. 中醫瘀血證診療大全. 北京:中國中醫藥出版社. 1996;184-9.
35 신재용. 方藥合編解說. 서울:성보사. 1989;99-100.
36 許浚. 東醫寶鑑. 서울:남산당. 1989;372.
37 Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R. ApoE defidient mice develop lesion of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb. 1994;14:133- 40.   DOI
38 Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 1992;258:468-71.   DOI
39 Ross R. Atherosclerosis-An inflammatory disease. New Engl J Med. 1999;(340):115-26.
40 서울대학교의과대학 내과학교실. 최신지견 내과학(I). 서울:고려의학. 2003;540-53.
41 오구택. 형질전환모델동물을 이용한 동맥경화증의 연구 및 치료제 개발. Biochemistry news. 2002;22(1):12-21.
42 Ross R. The pathogenesis of atherosclerosis. a perspective for the 1990's. Nature. 1993:(362): 801-9.
43 Han EJ, Kim CJ, Hong SU, Kim YB. A case of treatment of Livedo Vasculopathy. The Journal of Korean Oriental Medical Ophthalmology & Otolaryngology & Dermatology. 2001;14(2):84-88.
44 Cybulsky MI, Gimbrone MA. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991; (251):788-91.
45 Cushing SD, Berliner JA, Valente AJ, Territo MC, Navab M, Parhami F, et al. Minimally modification low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci USA. 1990;(87):5134-8.
46 Chawla A, Boisvert WA, Lee CH, Lafitte BA, Barak Y, Joseph SB, et al. A PPAR LXR ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell. 2001;(7):161-71.
47 전병렬. 한국인의 고지혈증 및 동맥경화증 질환 의 시대적 변천. J Korean Soc Lipidol Atheroscler. 2001;11(1):29-38.
48 Jeon WK, Kim JH, Lee AY, Kim HK. Inhibition of whole blood platelet aggregation from traditional medicines. Korean Journal of Oriental Medicine. 2003;9(2):55-67.   과학기술학회마을
49 경희의료원. 경희한방처방집. 서울:나도기획. 2007 :399.
50 통계청. 2007년 사망원인 통계연보. 서울;통계청. 2008.
51 Naito HK. Atherogenesis:current topics on etology and risk factors. Clin. Chem. 1995;41(1):132-3.