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1 대한내과학회지 : 제 권제 호 00 Helicobacter pylori 연관만성위염환자에서고려홍삼치료의효능에대한무작위연구 아주대학교의과대학소화기내과학교실및해부병리학교실, 분당제생병원소화기센터 김덕기 이정아 김영배 이기명 함기백 =Abstract= A randomized controlled trial assessing Korea red ginseng treatment of Helicobacter pylori-associated chronic gastritis Deog Ki Kim, M.D., Jeong A Lee, B.S., Young Bae Kim, M.D. Kee Myung Lee, M.D. and Ki Baik Hahm, M.D. Department of Gastroenterology and Anatomic Pathology, Ajou University School of Medicine, Suwon and Center for Gastroenterology, Bundang Jesaeng Hospital, Seongnam, Korea Background : As Korea red ginseng has been reported to show a significant protective effect against H. pylori-induced cytotoxicity and DNA damage in vitro, we designed a study to assess the efficacy of red ginseng treatment in patients with H. pylori-associated chronic gastritis. Methods : A total of 84 patients with H. pylori-associated chronic gastritis were recruited and randomly divided into two groups. During the trial, 4 patients out of 4 patients in the placebo control group and 6 patients out of 4 patients in the red ginseng group completed the protocol. The patients received a one week triple therapy for the eradication of H. pylori and then received either placebo capsules that were composed of flour for the placebo group or red ginseng capsules for the treatment group, which were administered for 0 weeks. An endoscopic examination of gastritis with a visual analogue scale, a test for detection of H. pylori, immunohistochemistry of 8-OHdG, the 8-OHdG immunohistochemical staining for assessing oxidative DNA damage and TUNEL staining for apoptosis were performed, respectively. Results : H. pylori eradication rates were augmented in the red ginseng group as compared to the placebo group (9.% in the red ginseng group and 9.4% in the placebo group), but there was no statistical significance (p=0.4). For an analysis of gastritis based on Updated Sydney System, the red ginseng group showed significant improvement in neutrophil infiltrations (p=0.008) and intestinal metaplasia (p=0.005). An attenuation of 8-OHdG immunohistostaining after treatment was seen more frequently in the red ginseng group (p<0.00). An attenuation of DNA damage and apoptosis was seen for the red ginseng group as compared to the placebo group (p<0.00). Conclusions : Supplementary administration of red ginseng augmented eradication rates of H. pylori, attenuated gastric inflammation, and reduced oxidative DNA damage and apoptosis, suggesting the clinical usefulness of red ginseng.(korean J Med :0-8, 00) Key Words : Red ginseng, Helicobacter pylori, Chronic gastritis Received : Accepted : Correspondence to : Ki-Baik Hahm, M.D., Center for Gastroenterology, Bundang Jesaeng Hospital, 55- Seohyeon-dong, Bundang-gu, Seongnam 46-4, Korea hanhmkb@hotmail.com * This stusy was granted from the Korea Ginseng Society - 0 -

2 -Deog Ki Kim, et al : Red ginseng supplement in the treatment of H. pylori-chronic gastritis - 서론 비침습적인그람음성균인 Helicobacter pylori (H., ) pylori) 는만성위염및소화성궤양의중요한원인이며 International Agency for Research on Cancer (IARC) 에서는 H. pylori를명확한발암인자 (group carcinogen) 로분류하였다 ). 근간의연구에서는만성염증이 H. pylori 연관암형성과정과발생에결정적인역할을하는데이는만성염증이암유발, 암세포의성장과생존에적합한전암미세환경을제공하기때문에 H. pylori 연관암을예방하기위해서는위염의원인이되는균을제균하거나염증을약화시키는방법이필수적이다 4, 5). 그렇지만 H. pylori 감염과위암발생과의연관성에대한많은연구에도불구하고 H. pylori 제균치료가위암예방을할수있는지에대해서는아직까지확실한답이없고 6) 오히려최근연구에서는 H. pylori 제균치료만으로는위암의위험을줄이지못한다고보고했다 ). 그러므로위암발생에서원인적인역할을하는 H. pylori 제균이외에더효과적으로 H. pylori와연관된위염의진전을막고, 위염의정도를감소시킬수있는또다른치료의필요성이대두되었다. 인삼 (Panax ginseng C.A. Meyer) 은오갈피나무과 (Araliaceae) 인삼속 (Panax) 에속하는다년생초본류이며, 말리지않은인삼을증숙하여건조한것이홍삼으로수천년간경험적인효능에의해건강식품과생약제로사용되고있다 8). 현재까지알려진인삼의효능은항산화 9), 항균 0) 그리고항염 ) 효과인데, 구체적으로는인삼에존재하는성분중진세노사이드 (ginsenoside) Rb은지질다당질 (lipopolysaccharide) 로유도된 tumor necrosis factor-alpha (TNF-a) 의발현을억제하고 ), 산성다당체 (acidic polysaccharide) 는인간위상피세포에대한 H. pylori의부착 (adhesion) 을방해하며 ), 인삼의대표적인폴리아세틸렌성분중홍삼에존재하는특이한성분인 panaxytriol 은실험적으로 H. pylori를억제할수있고이의 MIC (minimal inhibitory concentration) 는 50 microgram/ml으로알려져있다 0). 본저자들의이전연구결과녹차나홍삼의 H. pylori 감염에대한뚜렷한분자생물학적보호효과가있음을알게된점과홍삼이수용체신호전달차단으로 H. pylori에대한역할과기전, 그리고위점막손상에서의효능을실험적으로보고하였다 4, 5). Placebo group (n=4) H. pylori eradication for wk & Placebo (9 capsule/d) for 0 wks Per protocol (n=4) Recruit (n=88) Intention to treat (n=84) Ineligible (n=4) Red ginseng group (n=4) H. pylori eradication for wk & Red ginseng extract (. g/d) for 0 wks Per protocol (n=6) Endoscopy with biopsy, blood chemistry, rapid urease test, pathology, urea breath test Visit for symptom change, quality of life check, side effects and compliance Figure. Patient recruitment and protocol for randomized controlled trial. Eighty eight patients gave informed consent for the current trial, but four were found to be ineligible. Eighty four patients were randomly divided into two groups, a placebo control and the red ginseng group. All patients were scheduled to have performed two times an endoscopic examination and blood chemistry tests. The patients received a one week triple therapy for the eradication of H. pylori; for the placebo control group patients received placebo capsules containing flour (nine capsules/day, 0 weeks) and for the red ginseng group, patients received red ginseng capsules (00 mg/capsule containing red ginseng extracts,. g/day, 0 weeks). The number of patients per protocol was 4 for the placebo control group (8.0%) and 6 for the red ginseng group (85.%). The main causes of exclusion were denial to participate in follow-up endoscopy and withdrawal due to the side effects of the drug. 이러한배경하에저자들은본연구에서 H. pylori 연관만성위염환자에서 H. pylori 제균요법후 0주간의보충적인홍삼투여가임상적으로 H. pylori 제균율변화, Updated Sydbey System으로 scoring 한위염 score 변화, 산화적 DNA 손상그리고세포자멸사에대해어떤효능을나타내는지알아보고자하였다.. 대상 대상및방법 소화불량또는상복부불편감으로아주대학교의과대학부속병원에내원하여상부위장관내시경검사로 H. pylori 감염연관만성위염이확인된환자에서임상실험에참여할것을문서로동의하고, 동의서에서명한날짜를기준으로최소 개월이전에약물투약이없는환자 88명을대상으로하였다. 본연구는아주대학교의료원 IRB의승인 ( 승인번호 : 0-00) 을받았으며동의서를 - -

3 - 대한내과학회지 : 제 권제 호통권제 55 호 00 - 제출한 88명의환자중 4명이 H. pylori 감염의불확실성때문에실험에서제외되었다. 최종적으로 84명환자가대상이되었고이들을무작위로 4명의위약대조군과 4명의홍삼군으로나누었으며, 위약대조군중 4명이, 홍삼군중 6명이전체실험을만족하였다 ( 그림 ).. 방법 ) 치료군과대조군의약물투여위약대조군에는 H. pylori 제균 제요법 (pantoprazole 40 mg, bid + amoxicillin g, bid + clarithromycin 500 mg, bid) 을 주간투약후위약 (9캅셀 ( 동일캅셀의밀가루포함 / 일, 0주 ) 을투약했으며홍삼치료군에는동일한 H. pylori 제균 제요법후홍삼캅셀 ( 홍삼추출물 00 mg/ 캅셀 ( 한국인삼공사제공 ),. g/ 일, 0주 ) 을투약하였다. ) 위염의육안적인평가및 H. pylori 검출모든환자에게서두번의상부위장관내시경검사를시행하여위염의정도, 유형, 분포를서술하였다. 치료시작전과치료후즉 주에전정부의대만과소만부위에서 점, 위체부의대만과소만에서 점을생검하여생검조직 점은 CLO (rapid urease test) 를위해, 나머지 점은 H&E, Giemsa, immunohistochemical 염색을위해모두사용하였다. 모든환자에서실험시작시와종료후 H. pylori 진단을위하여 CLO 검사, 요소호기검사 (UBT검사 ), Giemsa 염색으로시행하였고, 이들세가지 H. pylori 진단검사모두에서음성으로판정되었을때균의음전위라고정의하였다. ) 조직학적평가 (Updated Sydney system) 위체부와전정부의생검조직으로 Updated Sydney system ) 에의거하여조직학적진단과등급을평가하였다. 급성염증의지표로서호중구의침윤정도를정상, 경증, 중등증, 중증으로등급을나누고 0,,,, 4, 5로점수화하였고, 만성염증의지표로서는단핵구의침윤, 그리고위축과장상피화생정도를역시같은방법으로등급화하여평가하고 chi squared test로통계처리하였다. 4) 8-hydroxydeoxyguanosine (8-OHdG) 를위한면역조직화학법위점막에서 oxidative DNA 손상을보기위해 8-OHdG 항체를이용한면역조직화학법을이용하였다. 각위생검조직을 5-m 두께절편으로만들어 8-OHdG 항체 (Chemicon) 와 차항체인 biotinylated anti-mouse IgG 으로 시간동안반응시켰다. 발색을위해서 avidinbiotin peroxidase method (ABC Elite kit, Vector Laboratories, Burlingame, CA) 을이용하였고, chromogen 으로 AEC (Zymogen, CA) 을사용하였다. 8-OHdG 면역염색정도 (intensity) 의점수화는조직에서위샘의염색정도에따라 0: 위샘염색안됨, : 위샘의 /4 이하염색 ( 00 magnified field), : /4 ~/4 염색, : /4~/4 염색, 4: /4 이상위샘의염색으로나타내었다. 5) 세포자멸사 (apoptosis) 의검출 (TUNEL method) Terminal deoxynucleotidyl transferase (TdT) FragEL DNA fragmentation detection kit (Oncogene Research Products, Darmstadt, Germany) 를이용해세포자멸사를검사하였다. 파라핀에고정된조직에서파라핀을제거한후 proteinase K (0 mg/ml in PBS) 로상온에서 0분간분해한후세척하였다. 조직절편을 equilibration buffer에서 0분간반응시킨후, TdT 효소로 에서 시간동안처리하였으며 methyl green 으로대조염색하였다. TUNEL로염색한절편들을저배율 ( 00 magnified field) 로검색하여 TUNEL 양성세포의수를평가하였다. 결과. 대상군의임상적특징각군의평균연령은위약대조군이 5.4±0.5세, 홍삼군은 48.0±0.5세이고남녀비는위약대조군에서 4:0, 홍삼군에서 :4이었다 ( 표 ).. H. pylori 제균율의변화 H. pylori 제균 제요법을 주간투약후 0주간위약투약을마친위약대조군 4명중에서제균율은 9.4%, 홍삼캅셀 ( 홍삼추출물 00 mg/ 캅셀,. g/ 일, 0주 ) 투약을마친홍삼군 6명중에서제균율은 9.% 로홍삼추가투여군에서헬리코박터제균율의상승이관찰되었으나통계적유의성은없었다 (p<0.4, 그림 )( 그림 ). - -

4 - 김덕기외 인 : Helicobacter 연관만성위염에서고려홍삼투여효능 - Table. Demographic and clinical characteristics of the study subjects. Mean age (years) Male : Female Endoscopic finding Hyperemia Erosion Atrophy Compliance PP, per protocol; ITT, intention to treat Placebo group (n=4) 5.4±0.5 4: % 4 (PP)/4 (ITT) Red ginseng group (n=6) 48.0±0.5 : % 6 (PP)/4 (ITT). 위염의조직학적변화실험전위약대조군 (n=4) 과홍삼군 (n=6) 의내시경소견차이는없었고 ( 표 ), 만성위염의병리학적 score 에서도호중구침윤의평균값이위약대조군대홍삼군이.9±. 대.9±.4, 단핵구침윤의평균값이.±0.4 대.0±0.6, 장상피화생평균값이.8 ±.99 대.56±0.86, 그리고위축의평균값이.0±0. 대.0±.0으로차이가없었다 ( 표 ). 치료 주후병리학적 score 분류상 등급이상으로호중구침윤이호전된경우는위약대조군에선 44.%, 홍삼군에선 5.0% 로통계적으로의미있는소견을보였다 (p<0.008). 또한병리학적 score 분류에서 등급이상으로단핵구침윤이호전된경우는위약대조군에선 4.%, 홍삼군에선.8% 로홍삼군에서더많이호전되었으나통계적유의성은없었다 (p=0.89). 위축과장상피화생점수의변화도관찰되었는데이들변화는 등급이아닌 등급이상장상피화생호전된경우는위약대조군에선 4.8%, 홍삼군에선 48.5% 로통계적으로의미있는소견을보였으나 OR=.8, p=0.4 P < % 9.4% Placebo group Red ginseng group (p=0.005), 한등급이상위축이호전된경우는위약대조군에선 8.5%, 홍삼군에선 4.4% 으로홍삼군에서호전율이통계적으로유의하게높았다 (p=0.049) ( 그림 ). 4. 산화 DNA 손상과 DNA 변이에대한홍삼의효과 H. pylori 연관만성위염환자에서위점막의산화 DNA 손상을보기위해시행한 8-OHdG 면역조직화학염색에서헬리코박터에감염된경우대부분위샘상피세포의세포질과핵모두에의미있게염색되는소견을보였다. 현미경으로관찰하여측정한평균 8-OHdG 양은치료전두군간에는차이가없었다. 치료후위약대조군에서의 8-OHdG 는통계적으로의미있는감소소견을보였고 (p=0.04), 홍삼군에서 8-OHdG의감소는위약대조군보다더욱현저하였다 (p<0.00)( 그림 4). 5. 세포자멸사에대한홍삼의효과표본조직에서 TUNEL method 로본세포자멸사는치료전두군간에차이는없었으며치료후 TUNEL 양성세포의감소는위약대조군에서도통계적으로의미있는감소소견을보였고 (p<0.000) 이는헬리코박터균의제균에의한것인데이러한변화는홍삼군에서도통계적으로의미있는 TUNEL 양성세포의감소를보였다 (p<0.000). 치료후두군에서의 TUNEL 양성세포의수를비교하였을때같은헬리코박터균이박멸된경우에서도위약대조군보다홍삼군에서더욱현저하게적었다 (p<0.000)( 그림 5). 0 Figure. The H. pylori eradication rate according to the treatment groups. 고찰 H. pylori 는감염된환자에서만성위염이나소화성 - -

5 -The Korean Journal of Medicine : Vol., No., 00 - Table. Pathological grading of gastritis before treatment. Neutrophils 5 4 Mononuclear cells 4 Intestinal metaplasia > 0 Atrophy > 0 Placebo group (n=4).9±. 6.± ±.99.0± Red ginseng group (n=6).9± ± ± ± a) b) Patients achieving improvement > scores (neutrophil infiltrations) p= % (/6) p= % (5/4) 5.0% 4.% (9/6) (8/4) c) Placebo Red ginseng d) Placebo Red ginseng Patients achieving improvement > scores (gastric atrophy) 8.5% (5/) Placebo *p= % (4/) Red ginseng Patients achieving improvement > scores (mononuclear cell infiltrations) Patients achieving improvement > scores (intestinal metaplasia) 4.8% (4/) Placebo *p= % (6/) Red ginseng Figure. The improvement of the pathological grading of gastritis according to the treatment groups

6 -Deog Ki Kim, et al : Red ginseng supplement in the treatment of H. pylori-chronic gastritis P p=0.04 P p< P p<0.000 P p<0.000 P p< Placebo group Red ginseng group 0 Placebo group Red ginseng group Pre Post Pre Post 0 Pre Post Pre Post Treatment Figure 4. The change of 8-OHdG intensity according to the treatment groups. Figure 5. The change of TUNEL positive cells according to treatment groups. 궤양의중요한원인인자이며한번감염되면자연적으로치유되는경우는드물고대부분거의평생동안감염이지속되어위점막조직의파괴를일으킨다 ). H. pylori 감염과위암발생과의연관성에대한연구로는역학조사를통해위암발생률이높은나라에서 H. pylori 감염률이높다는사실 8), Uemura 등이 년간의 cohort study 에서 H. pylori가위암을유발한다는보고 9) 그리고조기위암의내시경적제거후 H. pylori 제균이 차위암발생을감소시킨다는연구 0) 등으로 H. pylori 감염이위암발생에서원인적인역할을하기때문에위염원인이되는이균주를박멸시키는것이필수적일것이라고생각하였으나최근연구 ) 에서는 H. pylori 제균치료만으로는위암의위험을줄이지못한다고하여위암발생에서원인적인역할을하는 H. pylori 제균이외에더효과적으로 H. pylori 연관위염의진행을막고위염을감소시킬수있는새로운치료방법이나약제의개발이필요하게되었다. 최근 H. pylori 감염에제균과위염경감을위해보조요법으로생균제 (probiotics) ), H. pylori 백신 ), 장기복용할수있는식물성화학물 (phytochemicals) 에대한연구가이루어지고있는데본저자들은이전의전향적인연구로 H. pylori 연관소화궤양질환을가진 5명의환자들을대상으로 proton pump inhibitor (PPI) 와 amoxicillin 투여군과 PPI와 amoxicillin 그리고항산화, 항염증및 prostaglandin 유도기능이있는것으로알려진 rebamipide 투여군간의제균율을상호비교하였는데결과적으로 H. pylori 제균요법에 rebamipide 를추가하므로서양적및질적으로 H. pylori 제균율을증가시키고 H. pylori로인한산화스트레스와사이토카인 (IL-6, TNF-, IL-8, GRO-, RANTES) 의감소를확인하 였고 ), 실험실적연구로 H. pylori에의한위점막손상에서홍삼추출물이수용체신호전달차단으로세포사멸을방해하고, NF-κB의 DNA 결합을감소시키는위점막보호의효능을보고하여 5) 본연구에서는 H. pylori 연관만성위염환자에서 H. pylori 제균요법후보충적인홍삼투여의효능을임상적으로알아보았다. 본연구에서는 H. pylori 제균요법후보충적인홍삼투여 (. g/day for 0 weeks) 가제균율에미치는영향을본결과위약대조군 4명중에서제균율은 9.4%, 홍삼군 6명중에서제균율은 9.% 로비록통계적유의상은없었으나 (p=0.4) 제균요법후홍삼의보충은적어도제균치료실패율을감소시키는긍정적인효과를기대할수있는것으로보인다. 또한홍삼이직접적인향균작용이있을수있다는보고에근거하여병행하여추가로시행한실험에서홍삼만을 8주간단독으로투약한 8명중 4명에서제균효능 (0.5%) 이있었으나대조군에서는관찰기간중에제균된예가없는사실에서고려홍삼이균자체를박멸시키는것인지, 균증식만을억제하는지아니면제균요법의취약성을보상하는것인지에대해서는명확한결과를입증하기위한추가연구가필요하리라생각되지만본연구결과를종합하면제균치료율상승이나제균자체에유익하다는결론을유추할수있겠다. 오랜기간동안의 H. pylori 감염이위점막의위축, 장상피화생과같은조직학적변화를일으키는데 Ito 등 4) 에의하면 H. pylori 제균요법후위점막의위축과장상피화생이오랜기간후가역적으로호전될수있음을보고하였고 Correa 등 5) 에의하면위점막의위축, 장상피화생을가진위암위험군에서 H. pylori 제균요법과항산화제투여가위암발생의위험을감소시킬수있음을보고하였는데본연구에서는 H. pylori 제균요법과 0주 - 5 -

7 - 대한내과학회지 : 제 권제 호통권제 55 호 00 - 간의보충적인홍삼투여가제균요법만시행한대조군에비해현저한위염의호전뿐만아니라장상피화생의호전도관찰되어이는장기적인홍삼의투여가전구병변에서예방적인기능의가능성을짐작할수있게한다. 994년 WHO IARC 에서는 H. pylori가인간에서 group 의발암물질이며위암발생의원인적인역할을하는유기물로결론지었다 ). H. pylori 감염은위암발생에중요한많은요소즉, 위액의비타민 C의양, 반응성산화대사물, 상피세포의증식, MMR 단백질그리고 ornithine decarboxylase 활성의감소를유발한다. 그중산소유리기에의한 DNA 손상이잠재적으로돌연변이와발암유발가능한유전자변이를유발하는매우유해한결과를가진다 6). 최근 8-hydroxydeoxyguanosine (8-OHdG) 이나 8- oxodeoxyguanosine (8-OXdG) 가손상장기에서산화 DNA 손상을반영하는민감한표지자로받아들여진다. 8-OHdG는복제시와 G-T transversions 시불일치를유발할수있다, 8). DNA 중합효소에의해 8-OHdG 함유 DNA의오독으로 RNA 중합효소로 RNA 합성시 poly d (A-T), d (A-T) 주형에 UTP 대신 8-OHdG가 RNA로일체화된다. 그래서 8-OHdG 는 adenine의염기쌍을형성한다. 그러므로 DNA에서 8-OHdG의측정은반응산소대사물로인한손상측정에매우유용하다. 최근연구에서 H. pylori 감염에의한 DNA 산화손상은 8-OHdG의증가및핵내로의이동을유도함을관찰하였고 9) 본저자들은 H. pylori 제균후 8-OHdG 양의가역성을이전연구에서보여주었다 0). 이번연구에서도위점막조직의 8-OHdG 면역조직화학염색에서대부분위샘상피세포에서세포질과핵모두에서의미있는염색을보였고성공적인 H. pylori 제균은통계적으로의미있는 8-OHdG 감소를보이며 (p=0.04), 8-OHdG 감소는위약대조군보다홍삼군에서더욱현저하였으므로고려홍삼의장기복용은 H. pylori 감염된위샘을 DNA 손상으로부터구제할수있음을나타낸다. H. pylori 감염은위상피의세포자멸사를유도하는데이는위상피세포소실의직접원인으로위산분비교란, 위선감소등으로질환의발생과관련되고암화를촉진시키는것으로추론된다. H. pylori가세포자멸사를유발하는기전에대하여아직정확히알려져있지않으나최근연구에서는 H. pylori vaca가사립체로부터 cytochrome C를방출하여 caspase-를활성화하고 PARP 의단백분해분할로 cytochrome C-의존세포자멸사를매개하고 ) H. pylori 감염은 mitogen-activated protein kinase (MAPK) 중 extracellular signal regulated kinases (ERK) 를활성화시켜세포자멸사를유도하는 데 ) Park 등 ) 의연구에서는인삼의사포닌 (saponin) 성분인진세노이드 Rh (ginsenoid Rh) 가간암세포에서 caspase- 를활성화시켜 PARP 의단백분해분할로 cytochrome C-의존세포자멸사함을보고하였고, 본저자들은이전연구 5) 에서홍삼이 ERK의활성화를억제함을보고한바있다. 이번임상연구에서도 0주간홍삼을투여한군에서통계적으로의미있는 TUNEL 양성세포의감소를보였는데이는 H. pylori 제균요법만시행한군에비해더욱의미있는감소소견을보여 (p<0.000) 홍삼이임상적으로 H. pylori로인한위점막의세포자멸사를감소시킴을알수있다. 결론적으로 H. pylori 연관위염환자에서 H. pylori 제균요법후 0주간의보충적인홍삼투여가임상적으로 H. pylori 제균율을향상시키고 H. pylori 감염이유발한산화스트레스로부터 DNA 보호기능을나타내고세포자멸사를억제함으로 H. pylori 연관된위암전구병변에서의예방적인기능의가능성을짐작할수있으나이를확인하기위해서는추후장기적인대단위임상실험이필요하리라생각한다. 요약목적 : H. pylori가만성위염과위암발생에관련되어있다는많은연구에도불구하고 H. pylori 제균치료만으로는위암발생의위험을줄이지못함으로인해더효과적으로 H. pylori 연관위염의진행을막고위염을감소시킬수있는치료가요구된다. 홍삼의 H. pylori 감염에대한효과와위점막손상에서의효능이실험적으로보고되어, 이번연구의목적은 H. pylori 연관만성위염환자에서 H. pylori 제균요법후보충적인홍삼투여가임상적으로미치는효능을알아보고자하였다. 방법 : 상부위장관증상으로상부위장관내시경검사및 H. pylori 감염여부검사로 H. pylori 연관만성위염이확인된환자 84명을대상으로 4명씩무작위로위약대조군과홍삼군으로나누어 주간 H. pylori 제균 제요법후위약대조군에서는위약 (9캅셀/ 일, 0주 ) 을홍삼군에서는홍삼 ( 홍삼추출물 00 mg/ 캅셀,. g/ 일, 0주 ) 을투약후두군간의 H. pylori 제균율의변화, 위 - 6 -

8 - 김덕기외 인 : Helicobacter 연관만성위염에서고려홍삼투여효능 - 염의조직학적변화를비교하고위점막의산화 DNA 손상을보기위해 8-OHdG 면역조직화학염색과 comet assay를이용하여평가하고세포자멸사를 TUNEL method 로비교평가하였다. 결과 : H. pylori 제균율은홍삼추가투여군이위약군보다높았으나통계적유의성은없었다. 위염의조직학적변화중호중구침윤의감소 (p<0.008) 와장상피화생의호전도홍삼군에서통계적으로의미있는소견을보였다 (p=0.005). 치료전, 후의 8-OHdG 강도의변화는두군에서모두통계적으로의미있는감소소견을보였으며, 치료전후의 TUNEL 양성세포의수는두군에서모두통계적으로의미있는감소소견을보였고위약대조군보다홍삼군에서더욱현저하게감소하였다 (p<0.000). 결론 : H. pylori 연관위염환자에서 H. pylori 제균요법후보충적인홍삼투여가위암발생에서원인적인역할을하는 H. pylori 제균이외에더효과적으로 H. pylori 연관위염의진행을막고위염을감소시킬수있는유용한치료로생각한다. 중심단어 : 홍삼, Helicobacter pylori, 만성위염 REFERENCES ) Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet :-5, 984 ) Hentschel E, Brandstatter G, Dragosics B, Hirschl AM, Nemec H, Schutze K, Taufer M, Wurzer H. Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer. N Engl J Med 8:08-, 99 ) World Health Organization. Schistosomes, liver flukes and Helicobacter pylori: IARC working group on the evaluation of carcinogenic risks to humans. Vol 6. p., Lyon, IARC, 994 4) Davies GR, Rampton DS. Helicobacter pylori, free radicals and gastroduodenal disease. Eur J Gastroenterol Hepatol 6:-0, 994 5) Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentrich N, Sibley RK. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 5:-, 99 6) Correa P. A human model of gastric carcinogenesis. Cancer Res 48: , 988 ) Crespi M, Citarda F. Helicobacter pylori and gastric cancer: an overrated risk? Scand J Gastroenterol :04-046, 996 8) Liu CX, Xiao PG. Recent advances on ginseng research in China. J Ethnopharmacol 6:-8, 99 9) Shao ZH, Xie JT, Vanden Hoek TL, Mehendale S, Aung H, Li CQ, Qin Y, Schumacker PT, Becker LB, Yuan CS. Antioxidant effects of American ginseng berry extract in cardiomyocytes exposed to acute oxidant stress. Biochim Biophys Acta 60:65-, 004 0) Bae EA, Han MJ, Baek NI, Kim DH. In vitro anti-helicobacter pylori activity of panaxytriol isolate from ginseng. Arch Pharm Res 4:9-99, 00 ) Park EK, Choo MK, Han MJ, Kim DH. Ginsenoside Rh possesses antiallergic and anti-inflammatory activities. Int Arch Allergy Immunol :-0, 004 ) Smolinski AT, Pestka JJ. Modulation of lipopolysaccharide-induced proinflammatory cytokine production in vitro and in vivo by the herbal constituents apigenin (chamomile), ginsenoside Rb() (ginseng) and parthenolide (feverfew). Food Chem Toxicol 4:8-90, 00 ) Belogortseva NI, Yoon JY, Kim KH. Inhibition of Helicobacter pylori hemagglutination by polysaccharide fractions from roots of Panax ginseng. Planta Med 66:-0, 000 4) Lee KM, Yeo M, Choue JS, Jin JH, Park SJ, Cheong JY, Lee KJ, Kim JH, Hahm KB. Protective mechanism of epigallocatechin--gallate against Helicobacter pylori-induced gastric epithelial cytotoxicity via the blockage of TLR-4 signaling. Helicobacter 9:6-64, 004 5) Park S, Yeo M, Jin JH, Lee KM, Jung JY, Choue R, Cho SW, Hahm KB. Rescue of Helicobacter pylori-induced cytotoxicity by red ginseng. Dig Dis Sci 50:8-, 005 6) Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis: the updated Sydney System: International Workshop on the Histopathology of Gastritis, Houston 994. Am J Surg Pathol 0:6-8, 996 ) Dixon MF. Helicobactor pylori and peptic ulceration: histopathological aspects. J Gastroenterol Hepatol 6:5-0, 99 8) The EUROGAST Study Group. An international association between Helicobactor pylori infection and gastric cancer. Lancet 4:59-6, 99 9) Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, - -

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김범수

김범수 Analysis of Outcomes after Resection of Sarcomatous Hepatocellular Carcinoma Purpose: Sarcomatous hepatocellular carcinoma (HCC) is rare. Therefore, the clinicopathologic characteristics and prognosis