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Effect of Evodiae Fructus and Arecae Semen Mixture on Esophageal Mucosa in Chronic Acid Reflux Esophagitis
Biomed Sci Letters 2021;27:77-87
Published online June 30, 2021;  https://doi.org/10.15616/BSL.2021.27.2.77
© 2021 The Korean Society For Biomedical Laboratory Sciences.

Jin A Lee1,* , Mi-Rae Shin1,** , Hae-Jin Park2,** and Seong-Soo Roh1,†,**

1Department of Herbology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea
2DHU Bio Convergence Testing Center, Gyeongsangbuk-do 38610, Korea
Correspondence to: Seong-Soo Roh. Department of Herbology, College of Korean Medicine, Daegu Haany University, 136, Sincheondong-ro, Suseong-gu, Daegu 42158, Korea.
Tel: +82-53-770-2350, Fax: +82-53-768-6340, e-mail: ddede@dhu.ac.kr
*Graduate student, **Professor.
Received April 30, 2021; Revised June 9, 2021; Accepted June 14, 2021.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Reflux esophagitis (RE) is a disease that stomach contents, stomach acid, and pepsin continually refluxing and is curently increasing worldwide. This study was conducted to find natural materials that can reduce side effects and effectively treat RE. Animal experiments were conducted with a 1:1 (EA1), 1:5 (EA5) ratio of Evodiae Fructus and Arecae Semen known to be effective against reflux esophagitis. As a result of confirming the total lesion of the esophageal mucosa after EA1 or EA5 treatment in reflux esophagitis animals, it showed superior improvement compared to the REcontrol rats. In addition, by regulating the expression of MPO and NADPH oxidase, the activation of NF-κB was inhibited, and the expression of COX-1 and COX-2 was regulated. Moreover, its improved esophageal barrier function through regulating protein expressions of tight junction protein and MMPs/TIMPs. Taken together, a mixture of Evodiae Fructus and Arecae Semen can attenuate the damage to the esophageal mucosa that not only inactivationed the NF-κB through oxidative stress control, but also by regulating tight junctions and MMPs/TIMPs. This effect was more excellent in the 1:1 mixture (EA1) than in the Evodiae Fructus and Arecae Semen 1:5 mixture (EA5).
Keywords : Chronic acid reflux esophagitis, Evodiae Fructus, Arecae Semen, Inflammation, Tight junction
꽌 濡

뿭瑜섏꽦 떇룄뿼(Reflux esophagitis; RE)씠 뿬윭 媛吏 썝씤뿉 쓽븯뿬 쐞궛씠 뿭瑜섑빐 젏留 넀긽 諛 뿼利앹쓣 珥덈옒븯뒗 吏덊솚쑝濡, 뿰븯怨ㅻ(dysphagia), 냽벐由(heart burn), 뿭瑜섏쬆긽(regurgitation) 벑쓽 利앹긽쓣 룞諛섑븳떎(Yi et al., 1994). RE뒗 꽌援ъ뿉꽌 諛쒖깮 鍮덈룄媛 넂寃 굹굹怨 엳쑝硫, 꽌뼇씤뿉 鍮꾪븯뿬 븘떆븘씤뱾 쐞궛遺꾨퉬뒫씠 궙怨, 鍮꾨쭔솚옄媛 쟻쑝硫, 넂 븯遺떇룄 愿꾩빟洹쇱븬씠 넂 벑쓽 씠쑀濡 諛쒖깮 鍮덈룄媛 궙寃 굹굹怨 엳쑝굹(Baek et al., 2004) 理쒓렐 援궡뿉꽌룄 議곗씠뒗 蹂듭옣, 씉뿰, 깂궛쓬猷뚯쓽 鍮덈쾲븳 꽠痍 벑쓽 깮솢뒿愿 諛 吏諛⑹떇씠濡 씤븳 鍮꾨쭔씤援 利앷濡 씤빐 RE쓽 諛쒖깮 鍮덈룄媛 利앷븯怨 엳떎(Baek et al., 2004). RE 移섎즺瑜 쐞븯뿬 쐞궛 遺꾨퉬瑜 뼲젣떆耳쒖<뒗 H2 닔슜泥 李⑤떒젣 諛 PPIs 젣젣 벑쓽 泥섎갑씠 留롮씠 씠猷⑥뼱吏怨 엳쑝굹 씠윭븳 젣젣뱾 몴以 슜웾 諛 쑀吏 移섎즺 湲곌컙뿉 븳 젙蹂닿 遺덈챸솗븯硫, 蹂듭슜쓣 以묐떒븷 寃쎌슦 RE 솚옄뿉꽌 1뀈 씠궡 50~80%媛 옱諛쒗븯뒗 寃껋쑝濡 븣젮졇 엳뼱 옱諛 諛⑹瑜 쐞븳 옣湲곌컙 移섎즺뿉룄 遺옉슜씠 쟻 移섎즺젣쓽 媛쒕컻씠 븘슂븳 떎젙씠떎(Kim et al., 2011).

삤닔쑀(맫뙮맱; Evodiae Fructus)뒗 슫뼢怨(듃腰숂쭛; Rutaceae)뿉 냽븯뒗 삤닔쑀쓽 誘몄꽦닕 怨쇱떎쓣 留먮┛ 寃껋쑝濡 洹 꽦吏덉 媛(궄), 鍮(꽳), 쐞(긿)뿉 洹寃(閭며텚)븯硫(Yang et al., 2019; Kim et al., 2003), 븳諛⑹뿉꽌뒗 二쇰줈 嫄댁쐞(겈긿), 빐룆(鰲f캃) 벑뿉 궗슜릺뼱 솕떎(Yun et al., 2008). 삤닔쑀쓽 二쇱슂 꽦遺꾩쑝濡쒕뒗 evodiamine, rutaecarpine, evocarpine 벑씠 븣젮졇 엳怨(Yang et al., 2020), 빟由 슚뒫쑝濡쒕뒗 빆궛솕(Yang et al., 2020), 빆뿼利(Yun et al., 2008) 벑쓽 슚怨쇨 븣젮졇 엳쑝硫, 듅엳 씠쟾 뿰援щ 넻빐 삤닔쑀 臾 異붿텧臾쇱씠 湲됱꽦 諛 留뚯꽦 뿭瑜섏꽦 떇룄뿼뿉꽌 떇룄 젏留됱쓣 蹂댄샇븳떎뒗 뿰援 寃곌낵媛 諛앺議뚮떎(Kim and Roh, 2012; Lee et al., 2019).

鍮덈옉옄(茹녔쫽耶; Arecae Serum)뒗 빞옄굹臾닿낵(汝뺞쳷燁; Arecaceae/Palmae)뿉 냽븯뒗 鍮덈옉굹臾댁쓽 뿴留ㅼ씠떎(Lee et al., 2014). 鍮덈옉옄뒗 tannin, isoflavones 벑쓽 꽦遺꾩쓣 룷븿븯硫, 븳諛⑹뿉꽌뒗 二쇰줈 쉶異(썡윸), 蹂듬뙺李(끃깿넧꽮), 꽕궗(力꾤), 냼솕遺덈웾(易덂뙑畑㎬돬) 벑뿉 궗슜릺뼱 솕떎(Lin et al., 2020). 빟由 슚뒫뿉 븳 뿰援щ줈뒗 二쇰줈 쐞옣슫룞꽦(Zhang et al., 2020; Zhnag et al., 2017)怨 愿젴맂 뿰援ш 씠猷⑥뼱議뚯쑝硫, 삉븳 湲됱꽦 諛 留뚯꽦 뿭瑜섏꽦 떇룄뿼뿉꽌 떇룄 젏留됱쓣 蹂댄샇븳떎뒗 뿰援 寃곌낵媛 諛앺議뚮떎(Kim, 2019).

씠뿉 蹂 뿰援ъ뿉꽌뒗 湲됱꽦 諛 留뚯꽦 뿭瑜섏꽦 떇룄뿼뿉 슚怨쇨 엳떎怨 븣젮吏 삤닔쑀 鍮덈옉옄쓣 샎빀븯뿬 洹 샎빀臾쇱씠 留뚯꽦 뿭瑜섏꽦 떇룄뿼 룞臾쇱뿉寃 誘몄튂뒗 슚怨쇰 솗씤븯떎. 삤닔쑀 鍮덈옉옄쓽 諛고빀 1:1 諛고빀鍮 諛 븳諛⑹뿉꽌 냼솕媛 옒 릺吏 븡븘 굹굹뒗 蹂묒쬆씤 닔怨〓━(麗당뿢), 넀꽕(繇㎪퀎)뿉 궗슜릺뒗 諛고빀씤 1:5(삤닔쑀-鍮덈옉옄 = 1:1, 1:5) 諛고빀鍮꾨 궗슜븯쑝硫, 留뚯꽦 뿭瑜섏꽦 떇룄뿼뿉 븳 삤닔쑀-鍮덈옉옄 샎빀臾쇱쓽 슚뒫 솗씤 寃곌낵, 쑀쓽븳 寃곌낵瑜 뼸뿀쑝硫 씠뿉 븯뿬 蹂닿퀬븯뒗 諛붿씠떎.

옱猷 諛 諛⑸쾿

옱猷

떆猷: 蹂 떎뿕뿉꽌 궗슜븳 삤닔쑀 鍮덈옉옄뒗 샊湲고븳빟援(援, 븳援)뿉꽌 援ъ엯븳 寃껋쓣 깮빟洹쒓꺽吏묒뿉 留욎텛뼱 愿뒫寃궗瑜 吏꾪뻾븳 썑 빟쟾洹쒓꺽뿉 쟻빀븳 寃껊쭔 젙궛븯뿬 궗슜븯떎. 鍮덈옉옄 삤닔쑀瑜 媛곴컖 200 g뵫 遺꾩뇙븯뿬 利앸쪟닔 2,000 mL 泥④븳 썑 뿴깢 異붿텧湲곕 씠슜븯뿬 2떆媛 룞븞 異붿텧븯떎. 뼸뼱吏 異붿텧臾쇱 媛먯븬 異붿텧옣移섎줈 냽異뺥븯쑝硫, 룞寃 嫄댁“湲곕 씠슜빐 嫄댁“떆耳 뙆슦뜑(삤닔쑀; 15.66%, 鍮덈옉옄; 6.75%)瑜 뼸뿀떎. 뙆슦뜑뒗 -80꼦뿉꽌 蹂닿븯쑝硫, 궗슜 吏곸쟾 利앸쪟닔뿉 끃뿬 궗슜븯떎.

떆빟: 蹂 떎뿕뿉 궗슜븳 potassium phosphate monobasic, potassium phosphate dibasic, 2', 7'Dichlorofluorescein diacetate (DCFH-DA) Sigma-Aldrich Co. (St. Louis, MO, USA)뿉꽌 援ъ엯븯뿬 궗슜븯떎. Nitrocellulose membrane Amersham GE Healthcare (Little. Chalfont, UK)뿉꽌 援ъ엯븯怨, NADPH oxidase 2 (NOX2), p47phox, phospho-p38 MAPK (p-p38), phosphorylation of nuclear factor-kappa B p65 (NF-觀Bp65), phosphorylation inhibitor of nuclear factor kappa B alpha (p-I觀B慣), inhibitor of nuclear factor kappa B alpha (I觀B慣), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), Occludin, Claudin-1, Claudin-4, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-8 (MMP-8), tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue inhibitor of metalloproteinase-2 (TIMP-2) Histone, 棺-actin Santa Cruz Biotechnology (Dallas, CA, USA)濡쒕꽣 援ъ엯븯떎. p38 MAPK (p38)뒗 Cell Signaling Technology, Inc. (Beverly, MA, USA)뿉꽌 援ъ엯븯뿬 궗슜븯쑝硫, 2李 빆泥대뒗 GeneTex, Inc. (Irvine, LA, USA)뿉꽌 援ъ엯븯뿬 궗슜븯떎. Protease inhibitor mixture, ethylenediaminetetraacetic acid (EDTA)뒗 Wako Pure Chemical Industries, Ltd. (Osaka. Japan)뿉꽌 援ъ엯븯떎. ECL western blotting detection reagents뒗 GE Healthcare 濡쒕꽣 援ъ엯븯뿬 궗슜븯쑝硫, 떒諛깆쭏 젙웾쓣 쐞븳 BCA protein assay kit뒗 Thermo Scientific (Rockford, IL, USA)뿉꽌 援ъ엯븯떎.

떎뿕 룞臾: 5二쇰졊 닔而 Sprague-Dawley rat(븳諛붿씠삤留곹겕, 쓬꽦, 븳援)瑜 援ъ엯븯뿬 1二쇱씪 룞븞 떎뿕떎 솚寃쎌뿉 쟻쓳떆궓 썑 떎뿕쓣 吏꾪뻾븯떎. 룞臾 궗쑁떎 議곌굔 conventional system쑝濡 삩룄 22짹2꼦, 뒿룄 50짹5%, 紐낆븫二쇨린(light: dark cycle)뒗 12떆媛 二쇨린濡 議곗젅븯怨, 궗猷(議곕떒諛깆쭏 18% 씠긽, 議고쉶遺 8.0% 씠븯, 議곗꽟쑀 5.0% 씠븯, 議곗諛 5.0% 씠긽, 移쇱뒛 1.0% 씠긽, 씤 0.85% 씠긽, 移쇰ⅷ 0.55% 씠긽, 굹듃瑜 0.25% 씠긽, 留덇렇꽕뒛 0.15% 씠긽, NIH-41, Zeigler Bros, Inc., Gardners, PA, USA) 臾쇱 異⑸텇엳 怨듦툒븯떎. 蹂 뿰援щ뒗 룞臾쇱떎뿕쓽 怨쇳븰쟻, 쑄由ъ쟻 떦꽦 寃넗 諛 슚쑉쟻씤 愿由щ 쐞븯뿬 援ы븳쓽븰援 룞臾쇱떎뿕쑄由 쐞썝쉶(Institutional Animal Care and Use Committee: IACUC)쓽 듅씤(듅씤踰덊샇: DHU2021-026)쓣 諛쏆븘 吏꾪뻾릺뿀떎.

諛⑸쾿

留뚯꽦 뿭瑜섏꽦 떇룄뿼 쑀諛 諛 룞臾 泥섏튂: 18떆媛 젅떇 썑, Zoletil (Vibrac, France)쓣 蹂듦컯二쇱궗븯뿬 留덉랬떆耳곗쑝硫, 뿭瑜섏꽦 떇룄뿼 쑀諛쒖쓣 쐞븳 닔닠쓣 吏꾪뻾븯떎. 젣紐④린濡 蹂듬꽭쓣 젣嫄고븯뿬 蹂듦컙 젙以묐瑜 2 cm 젙룄 媛쒕났븯뿬 쐞遺(Fundus)瑜 釉붾옓 떎겕(2-0)떎濡 臾띔퀬, 쑀臾몃(pylorus)뿉뒗 latex ring (18-Fr Nelaton catheter, 2 mm in thickness)쓣 겮썙 latex ring씠 由ъ 븡룄濡 굹씪濡(5-0)떎濡 臾띠 썑 蹂듬쭑怨 뵾遺瑜 遊됲빀븯떎(Omura et al., 1999). 媛먯뿼쓣 以꾩씠湲 쐞빐 3씪媛 빆뿼利앹젣(Dexamethasone) 빆깮젣(Gentamicin sulfate)瑜 씗꽍븯뿬 뵾븯二쇱궗 븯쑝硫, 닔닠 24떆媛 썑 臾쇱쓣 怨듦툒빐二쇱뿀怨, 닔닠 48떆媛 썑遺꽣 궗猷뚮 怨듦툒빐 二쇱뿀떎. 1二쇱씪媛 쉶蹂듦린瑜 嫄곗튇 썑, 븘臾대윴 泥섏튂瑜 븯吏 븡 젙긽援(Normal), 留뚯꽦 뿭瑜섏꽦 떇룄뿼 쑀諛 썑 利앸쪟닔瑜 닾뿬븳 議곌뎔(Control), 留뚯꽦 뿭瑜섏꽦 떇룄뿼 쑀諛 썑 삤닔쑀-鍮덈옉옄(1:1) 샎빀臾 200 mg/kg瑜 닾뿬븳 援(EA1), 留뚯꽦 뿭瑜섏꽦 떇룄뿼 쑀諛 썑 삤닔쑀-鍮덈옉옄(1:5) 샎빀臾 200 mg/kg瑜 닾뿬븳 援(EA5) 珥 4洹몃9쑝濡 臾댁옉쐞 遺꾨쪟븯쑝硫, 紐⑤뱺 洹몃9 留ㅼ씪 씪젙븳 떆媛꾩뿉 紐몃Т寃 諛 궗猷 꽠痍⑤웾쓣 痢≪젙븯怨, 14씪媛 1씪 1쉶뵫 寃쎄뎄닾뿬 븯떎.

떇룄 넀긽 硫댁쟻 痢≪젙: 닔닠슜 媛쐞瑜 씠슜븯뿬 쟻異쒗븳 떇룄瑜 꽭濡쒕줈 젅떒븯떎. 젅떒맂 떇룄 궡遺瑜 saline쑝濡 꽭泥숉븳 썑 怨좎젙븯뿬 愿묓븰 뵒吏꽭 移대찓씪(DSCHX50V, Sony, Tokyo, Japan)瑜 씠슜븯뿬 珥ъ쁺븯떎. 넀긽맂 떇룄 젏留 痢≪젙 I-Solution lite (Innerview Co., Seongnam, Korea) 봽濡쒓렇옩쓣 씠슜븯뿬 떎젣 넀긽 遺쐞쓽 硫댁쟻쓣 痢≪젙븳 썑, 븘옒 떇쓣 씠슜븯뿬 넀긽 硫댁쟻쓣 굹궡뿀떎.

떇룄 넀긽 鍮꾩쑉=떇룄 넀긽 硫댁쟻떇룄 쟾泥 硫댁쟻100

삁븸遺꾩꽍: 蹂듬젙留μ뿉꽌 梨꾪삁븳 삁븸뿉꽌 삁泥쓣 遺꾨━븯뿬 GOT (Glutamic oxaloacetic transaminase), GPT (Glutamic pyruvic transaminase) 諛 MPO (Myeloperoxidase) level쓣 痢≪젙븯떎. GOT, GPT(븘궛젣빟, 꽌슱, 븳援) 諛 MPO (Biovision, Inc., CA, USA)뒗 떆빟꽭듃瑜 援ъ엯븯뿬 痢≪젙븯떎.

떇룄 議곗쭅 western blotting: 떇룄 議곗쭅쓽 꽭룷吏덉쓣 뼸湲 쐞빐 1.5 M sucrose, 0.1 M DTT, 100 mM Tris-HCl (pH 7.4), 15 mM CaCl2, 5 mM Tris-HCl (pH 7.5), 2 mM MgCl2, protease inhibitor cocktail쓣 泥④븳 buffer A瑜 꽔怨 議곗쭅 遺꾩뇙湲(tissue grinder) (Biospec Product, Bartlesville, OK, USA)濡 遺꾩뇙븳 썑 10% NP-40쓣 泥④븯뿬 븘씠뒪 쐞뿉꽌 30遺꾧컙 젙移섑븯쑝硫, 썝떖遺꾨━(12,000 rpm, 4꼦, 2遺)븯뿬 꽭룷吏덉쓣 룷븿븯怨 엳뒗 긽痢듭븸쓣 遺꾨━븯떎. 빑쓣 뼸湲 쐞빐 10% NP-40媛 뜑빐吏 buffer A뿉 몢 踰 뿹援ш퀬 100 關L쓽 buffer C (50 mM HEPES, 50 mM KCl, 1 mM DTT, 0.3 mM NaCl, 0.1 mM EDTA, 0.1 mM PMSF, 10% glycerol)瑜 泥④빐 옱遺쑀떆궓 썑 10遺꾨쭏떎 vortex瑜 3踰 븯떎. 洹 썑 썝떖遺꾨━(12,000 rpm, 4꼦, 10遺)븯뿬 빑쓣 룷븿븯怨 엳뒗 긽痢듭븸쓣 뼸뼱 -80꼦뿉꽌 媛곴컖 깋룞 蹂닿븯떎. 떇룄 議곗쭅 꽭룷吏덉쓽 NOX2, p47phox, p-p38, p38, p-I觀B慣, I觀B慣, iNOS, COX-1, COX-2, Occludin, Claudin-1, Claudin-4, MMP-2, MMP-8, TIMP-1, TIMP-2, 棺-actin 떒諛깆쭏怨 빑뿉꽌쓽 NF-觀Bp65, histone 떒諛깆쭏 諛쒗쁽쓣 痢≪젙븯湲 쐞븯뿬 12 關g쓽 떒諛깆쭏쓣 10~12% SDS polyacrylamide gel쓣 씠슜븯뿬 쟾湲곗쁺룞 썑, acrylamide gel쓣 nitrocellulose membrane쑝濡 씠룞떆耳곕떎. 以鍮꾨맂 membrane뿉 媛곴컖쓽 1李 antibody (1:1,000)瑜 泥섎━븯뿬 4꼦뿉꽌 overnight 떆궓 떎쓬 PBS-T濡 6遺꾨쭏떎 5쉶 꽭泥숉븯怨, 媛곴컖 泥섎━맂 1李 antibody뿉 궗슜릺뒗 2李 antibody (1:3,000)瑜 궗슜븯뿬 긽삩뿉꽌 2떆媛 諛섏쓳떆궓 썑, PBS-T濡 6遺꾨쭏떎 5쉶 꽭泥숉븯떎. 떒諛깆쭏 諛쒗쁽쓣 솗씤븯湲 쐞븯뿬 membrane쓣 enhanced chemiluminescence (ECL) 슜븸뿉 끂異쒖떆궓 썑, Sensi-Q2000 Chemidoc (Lugen Sci Co., Ltd., Seoul, Korea)뿉 媛먭킅떆耳 떒諛깆쭏 諛쒗쁽쓣 솗씤븳 썑, 빐떦 band瑜 ATTO Densitograph Software (ATTO Corporation, Tokyo, Japan) 봽濡쒓렇옩쓣 궗슜븯뿬 젙웾븯떎.

넻怨꾨텇꽍: In vivo쓽 닔移섎뒗 mean 짹 SD濡 몴떆븯쑝硫, SPSS (Version 25.0, IBM, Armonk, NY, USA)瑜 궗슜븯뿬 one-way analysis of variance (ANOVA) test瑜 떎떆븳 썑 least-significant differences (LSD) test濡 궗썑寃利앹쓣 떎떆븯뿬 媛 援곗쓽 룊洹 李⑥씠뿉 븳 넻怨꾩쟻 쑀쓽꽦쓣 *P<0.05, **P<0.01, ***P<0.001뿉꽌 寃利앺븯떎.

寃 怨

떇룄 넀긽 硫댁쟻 痢≪젙

떇룄 젏留됱쓽 넀긽쓣 솗씤븳 寃곌낵, 븘臾대윴 泥섏튂瑜 븯吏 븡 Normal援(0.58짹0.26%)뿉꽌뒗 떇룄 젏留됱쓽 넀긽 諛 沅ㅼ뼇씠 솗씤릺吏 븡븯쑝굹 Control援(7.74짹2.43%; P<0.001)뿉꽌뒗 떇룄 以묒븰遺뿉꽌 겙 沅ㅼ뼇씠 諛쒓껄릺뿀쑝硫, 븯遺떇룄뿉꽌 삉븳 沅ㅼ뼇쓣 솗씤븷 닔 엳뿀떎. 諛섎㈃, Control援곗뿉 鍮꾪븯뿬 EA1援곗뿉꽌 60% (P<0.001), EA5援곗뿉꽌 47% (P<0.01) 떇룄 넀긽씠 쑀쓽븯寃 媛먯냼븳 寃껋쓣 솗씤븯떎(Fig. 1).

Fig. 1. Surgical induction of chronic acid reflux esophagitis. A representative gross image; (A), esophageal ulcer ratio; (B). Normal group; Normal, chronic acid reflux esophagitis rats; Control, mixture of Evodiae Fructus and Arecae Semen in 1:1 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA1, mixture of Evodiae Fructus and Arecae Semen in 1:5 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA5. Significance: ###P<0.001 vs. Normal group, **P<0.01, ***P<0.001 vs. Control group.

GOT, GPT 諛 MPO 痢≪젙

GOT 諛 GPT 닔移 솗씤 寃곌낵, Normal援 鍮 Control援(P<0.001)뿉꽌 쑀쓽븯寃 利앷븯쑝硫, 듅엳 GPT쓽 닔移섍 Normal援 鍮 Control援곗뿉꽌 빟 2諛 겕寃 利앷븯떎. 諛섎㈃, Control援 鍮 EA1援(P<0.001)뿉꽌뒗 쑀쓽븯寃 媛먯냼븯뿬 Normal援곌낵 鍮꾩듂븳 닔移섎 굹깉쑝硫, EA5援곗뿉꽌 삉븳 GOT (P<0.01), GPT (P<0.001) 紐⑤몢 쑀쓽븯寃 媛먯냼븯떎. MPO 痢≪젙 寃곌낵, Normal援 鍮 Control援곗뿉꽌 69% (P<0.01) 쑀쓽븯寃 利앷븯쑝硫, Control援 鍮 EA1援곗뿉꽌 38% (P<0.05) 쑀쓽븯寃 媛먯냼븯뿬 Normal援곌낵 鍮꾩듂븳 닔移섎 굹깉쑝硫, EA5援 삉븳 30% (P<0.05) 쑀쓽븯寃 媛먯냼븯떎(Table 1).

Levels of GOT, GPT, and MPO in Serum

GOT (IU/L) GPT (IU/L) MPO (mU/mL)
Normal 32.89±2.90 6.11±0.62 0.53±0.07
Control 51.50±2.08### 11.52±0.34### 0.90±0.10##
EA1 38.26±1.63*** 6.00±0.46*** 0.56±0.11*
EA5 43.24±1.16** 8.28±0.42*** 0.63±0.07*

GOT; Glutamic oxaloacetic transaminase, GPT; Glutamic pyruvic transaminase, MPO; Myeloperoxidase. All date are expressed mean ± SD (n=8). Normal group; Normal, chronic acid reflux esophagitis rats; Control, mixture of Evodiae Fructus and Arecae in 1:1 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA1, mixture of Evodiae Fructus and Arecae in 1:5 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA5. Significance: ##P<0.01, ###P<0.001 vs. Normal group, *P<0.05, **P<0.01, ***P< 0.001 vs. Control group



媛 議곗쭅 western blotting

NADPH oxidase/iNOS 諛쒗쁽웾 遺꾩꽍: 떇룄 議곗쭅 궡 NADPH oxidase쓽 諛쒗쁽웾쓣 遺꾩꽍븳 寃곌낵, Normal援 鍮 Control援곗뿉꽌 NOX2 33%, p47phox 21% 쑀쓽븯寃 利앷븯쑝硫, Control援 鍮 EA1援곗 NOX2 p47phox 紐⑤몢 빟 50% 쑀쓽븯寃 媛먯냼븯쑝硫, EA5援곗뿉꽌 삉븳 NOX2, p47phox 紐⑤몢 빟 40% 쑀쓽븯寃 媛먯냼븯떎. 삉븳, iNOS쓽 諛쒗쁽 Normal援 鍮 Control援곗뿉꽌 41% 쑀쓽븯寃 利앷븯쑝硫, Control援 鍮 EA1援 41%, EA5援 27% 쑀쓽븯寃 媛먯냼븯뿬 EA1怨 EA5援 紐⑤몢 Normal援곌낵 鍮꾩듂븳 닔移섍퉴吏 媛먯냼븯떎(Fig. 2).

Fig. 2. Expression of NADPH oxidase and iNOS in esophagus. All date are expressed mean ± SD (n=8). Normal group; Normal, chronic acid reflux esophagitis rats; Control, mixture of Evodiae Fructus and Arecae Semen in 1:1 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA1, mixture of Evodiae Fructus and Arecae Semen in 1:5 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA5. Significance: #P<0.05, ##P<0.01 vs. Normal group, **P<0.01, ***P<0.001 vs. Control group.

뿼利 쟾궗씤옄 諛쒗쁽웾 遺꾩꽍: 떇룄 議곗쭅 궡 뿼利 쟾궗씤옄 p-p38, NF-觀Bp65, p-I觀B慣쓽 諛쒗쁽쓣 솗씤븳 寃곌낵, p-p38쓽 諛쒗쁽웾 Normal援 鍮 Control援곗뿉꽌 2諛 씠긽 쑀쓽븯寃 利앷븯쑝硫, Control援 鍮 EA1援곌낵 EA5援 紐⑤몢 36% 쑀쓽븯寃 媛먯냼븯떎. 삉븳, Normal援 鍮 Control援곗뿉꽌 NF-觀Bp65쓽 諛쒗쁽 82% 쑀쓽븯寃 利앷븯쑝硫, p-I觀B慣쓽 諛쒗쁽 56% 쑀쓽븯寃 利앷븯떎. 諛섎㈃, Control援 鍮 EA1援곗뿉꽌 NF-觀Bp65쓽 諛쒗쁽웾씠 37% 쑀쓽븯寃 媛먯냼븯쑝硫, EA5援곗뿉꽌 NF-觀Bp65 p-I觀B慣쓽 諛쒗쁽웾쓽 빟 30% 쑀쓽븯寃 媛먯냼븯떎(Fig. 3).

Fig. 3. Expression of inflammatory transcription factors in esophagus. All date are expressed mean ± SD (n=8). Normal group; Normal, chronic acid reflux esophagitis rats; Control, mixture of Evodiae Fructus and Arecae Semen in 1:1 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA1, mixture of Evodiae Fructus and Arecae Semen in 1:5 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA5. Significance: ###P<0.001 vs. Normal group, **P<0.01, ***P<0.001 vs. Control group.

Arachidonic acid 愿젴 씤옄 諛쒗쁽웾 遺꾩꽍: 떇룄 議곗쭅 궡 arachidonic acid 愿젴 씤옄씤 COX-1 諛 COX-2쓽 諛쒗쁽쓣 솗씤븳 寃곌낵, Normal援 鍮 Control援곗뿉꽌 COX-1 54% 쑀쓽븯寃 媛먯냼븯쑝硫, COX-2뒗 50% 쑀쓽븯寃 利앷븯떎. 諛섎㈃, COX-1쓽 諛쒗쁽 Control援 鍮 EA1援곗뿉꽌 53%, EA5援곗뿉꽌 68% 쑀쓽븯寃 利앷븯쑝硫, COX-2쓽 諛쒗쁽 Control援 鍮 EA1援 43%, EA5援 32% 쑀쓽븯寃 媛먯냼븯떎(Fig. 4).

Fig. 4. Expression of arachidonic acid proteins in esophagus. All date are expressed mean ± SD (n=8). Normal group; Normal, chronic acid reflux esophagitis rats; Control, mixture of Evodiae Fructus and Arecae Semen in 1:1 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA1, mixture of Evodiae Fructus and Arecae Semen in 1:5 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA5. Significance: ###P<0.001 vs. Normal group, *P<0.05, **P<0.01, ***P<0.001 vs. Control group.

Tight junction 諛쒗쁽웾 遺꾩꽍: 떇룄 議곗쭅 궡뿉꽌 tight junction 떒諛깆쭏씤 Occludin, Claudin-1 諛 Claudin-4쓽 諛쒗쁽쓣 솗씤븳 寃곌낵, Claudin-1쓽 諛쒗쁽 Normal援 鍮 Control援곗뿉꽌 59% 쑀쓽븯寃 媛먯냼븯쑝硫, Control援 鍮 EA1援곌낵 EA5援곗뿉꽌 60% 쑀쓽븯寃 利앷븯떎. 삉븳, Normal援 鍮 Control援곗뿉꽌 Occludin怨 Claudin-4쓽 諛쒗쁽씠 48% 쑀쓽븯寃 媛먯냼븯쑝硫, Control援 鍮 EA1援곌낵 EA5援곗뿉꽌 Occludin怨 Claudin-4쓽 諛쒗쁽씠 빟 40% 쑀쓽븯寃 利앷븯떎(Fig. 5).

Fig. 5. Expression of tight junction proteins in esophagus. All date are expressed mean ± SD (n=8). Normal group; Normal, chronic acid reflux esophagitis rats; Control, mixture of Evodiae Fructus and Arecae Semen in 1:1 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA1, mixture of Evodiae Fructus and Arecae Semen in 1:5 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA5. Significance: ###P<0.001 vs. Normal group, *P <0.05, **P<0.01 vs. Control group.

MMPs/TIMPs 諛쒗쁽웾 遺꾩꽍: 떇룄 議곗쭅 궡뿉꽌 MMP-2, MMP-8, TIMP-1 諛 TIMP-2쓽 諛쒗쁽쓣 솗씤븳 寃곌낵, Normal援 鍮 Control援곗뿉꽌 MMP-2쓽 諛쒗쁽씠 39% 쑀쓽븯寃 利앷븳 諛섎㈃ Control援 鍮 EA1援, EA5援 紐⑤몢 41% 쑀쓽븯寃 媛먯냼븯떎. 삉븳, MMP-8쓽 諛쒗쁽 Normal援 鍮 Control援곗뿉꽌 50% 쑀쓽븯寃 利앷븯쑝硫, Control援 鍮 EA1援곗뿉꽌 33%, EA5援곗뿉꽌 28% 쑀쓽븯寃 媛먯냼븯떎. TIMP-1怨 TIMP-2쓽 諛쒗쁽 Normal援 鍮 Control援곗뿉꽌 41% 쑀쓽븯寃 媛먯냼븯쑝硫, Control援 鍮 EA1援곗뿉꽌 30% 씠긽 쑀쓽븯寃 利앷븯怨, EA5援곗뿉꽌 35% 씠긽 쑀쓽븯寃 利앷븯떎(Fig. 6).

Fig. 6. Expression of MMP/TIMP proteins in esophagus. All date are expressed mean ± SD (n=8). Normal group; Normal, chronic acid reflux esophagitis rats; Control, mixture of Evodiae Fructus and Arecae Semen in 1:1 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA1, mixture of Evodiae Fructus and Arecae Semen in 1:5 ratio 200 mg/kg-treated chronic acid reflux esophagitis rats; EA5. Significance: ##P<0.01, ###P<0.001 vs. Normal group, *P<0.05, **P<0.01, ***P<0.001 vs. Control group.
怨 李

뿭瑜섏꽦 떇룄뿼(Reflux esophagitis) 씪諛섏쟻쑝濡 쐞븸쓽 뿭瑜섎줈 씤빐 뿼利앹씠 깮寃 떇룄 議곗쭅쓽 異쒗삁, 젏留 沅ㅼ뼇 諛 愿댁궗媛 씪뼱굹뒗 吏덊솚쑝濡쒖뜥 뿭瑜섏꽦 떇룄뿼쓽 썝씤 떎뼇븯吏留 씪諛섏쟻쑝濡 븯遺떇룄 愿꾩빟洹(lower esophageal spincter; LES)쓽 븬젰씠 궙븘 遺쟻젅븯寃 씠셿릺뼱 諛쒖깮븯뒗 寃껋쑝濡 븣젮졇 엳떎(Shin et al., 2016). 1990뀈源뚯留 븯뜑씪룄 슦由щ굹씪瑜 룷븿븳 븘떆븘 援媛뿉꽌뒗 뿭瑜섏꽦 떇룄뿼쓽 쑀蹂묒쑉씠 궙寃 굹궗湲 븣臾몄뿉 愿떖쓣 媛吏뜕 吏덊솚씠 븘땲쑝굹 2000뀈뿉 뱾뼱꽌硫댁꽌 쑀蹂묒쑉씠 吏냽쟻쑝濡 利앷븿쑝濡쒖뜥 뿭瑜섏꽦 떇룄뿼뿉 븳 愿떖怨 떎뼇븳 뿰援ш 利앷븯怨 엳뒗 異붿꽭씠떎(Cho et al., 2005). 씠뿉 蹂 뿰援ъ뿉꽌뒗 湲됱꽦 諛 留뚯꽦 뿭瑜섏꽦 떇룄뿼뿉 븯뿬 떇룄 젏留 蹂댄샇 슚怨쇨 엳떎怨 븣젮吏 삤닔쑀 鍮덈옉옄瑜 諛고빀븯쑝硫, 洹 샎빀臾쇱씠 떇룄 젏留됱뿉 誘몄튂뒗 슚怨쇰 븣븘蹂닿퀬옄 븯떎(Kim and Roh, 2012; Kim, 2019; Lee et al., 2019). 삤닔쑀 鍮덈옉옄쓽 諛고빀 1:1 諛고빀鍮 諛 븳諛⑹뿉꽌 냼솕媛 옒 릺吏 븡븘 굹굹뒗 蹂묒쬆씤 닔怨〓━(麗당뿢), 넀꽕(繇㎪퀎)뿉 궗슜릺뒗 諛고빀씤 1:5(삤닔쑀-鍮덈옉옄 = 1:1, 1:5) 諛고빀鍮꾨 궗슜븯떎.

癒쇱, 18떆媛 젅떇 썑 닔닠쓣 넻빐 SD rat뿉寃 뿭瑜섏꽦 떇룄뿼쓣 쑀諛쒗븯쑝硫, 1二쇱씪 룞븞 쟻쓳 湲곌컙쓣 嫄곗튇 썑, 2二쇨컙 삤닔쑀-鍮덈옉옄 1:1 샎빀臾(EA1)怨 1:5 샎빀臾(EA5)쓣 寃쎄뎄닾뿬븯뿬 떇룄 議곗쭅쓣 쟻異쒗븯떎. 쟻異쒗븳 떇룄 議곗쭅쓽 넀긽 硫댁쟻쓣 솗씤븳 寃곌낵, 븘臾대윴 泥섏튂瑜 븯吏 븡 Normal援곗뿉꽌뒗 떇룄 젏留됱쓽 넀긽 諛 沅ㅼ뼇씠 솗씤릺吏 븡븯쑝굹 Control援곗뿉꽌뒗 떇룄 以묒븰遺뿉꽌 겙 沅ㅼ뼇씠 諛쒓껄릺뿀쑝硫, 븯遺떇룄뿉꽌 삉븳 沅ㅼ뼇쓣 솗씤븷 닔 엳뿀쑝硫, Control援곗뿉 鍮꾪븯뿬 EA1援곗뿉꽌 60%, EA5援곗뿉꽌 47% 떇룄 젏留됱쓽 넀긽씠 쑀쓽븯寃 媛쒖꽑맂 寃껋쓣 솗씤븯떎(Fig. 1).

洹 썑, 삁븸뿉꽌 遺꾨━븳 삁泥쓣 씠슜븯뿬 GOT, GPT 諛 MPO쓽 닔移섎 솗씤븯떎. 媛꾩꽭룷媛 넀긽릺硫 GOT 諛 GPT 媛숈 슚냼뱾씠 삁以묒쑝濡 쓽윭굹 삁以 GOT, GPT 냽룄媛 긽듅븳떎(Fitzhugh and Nelson, 1948). 蹂 뿰援ъ뿉꽌 궗슜븳 鍮덈옉옄뒗 留롮 뿰援щ 넻빐 룆꽦씠 엳뒗 寃껋쑝濡 븣젮졇 엳뼱 궓슜븷 寃쎌슦 떖媛곹븳 遺옉슜씠 굹굹뒗 寃껋쑝濡 븣젮졇 엳떎(Roh and Seo, 2012). 씠뿉 蹂 뿰援ъ뿉꽌뒗 鍮덈옉옄쓽 룆꽦쑝濡 씤븳 룞臾쇱쓽 媛 넀긽 쑀臾대 솗씤븯湲 쐞븯뿬 삁以 GOT 諛 GPT쓽 닔移섎 솗씤븳 寃곌낵, 뒪듃젅뒪 諛 留뚯꽦 뿭瑜섏꽦 떇룄뿼 닔닠 怨쇱젙뿉꽌 GOT GPT 닔移섍 EA1援곗뿉꽌 쑀쓽븯寃 媛먯냼븯뿬 Normal援곌낵 鍮꾩듂븳 닔移섎 굹깉쑝硫, EA5援곗뿉꽌 삉븳 GOT, GPT 紐⑤몢 쑀쓽븯寃 媛먯냼븯떎(Table 1).

MPO (myeloperoxidase)뒗 硫댁뿭 泥닿퀎쓽 빑떖 슂냼씠硫, 긽泥 諛 媛먯뿼遺쐞뿉꽌 蹂묒썝泥댁뿉 븳 諛⑹뼱瑜 쐞븯뿬 샇以묎뎄濡쒕꽣 諛⑹텧릺뼱 媛먯뿼쓽 移섎즺뿉 룄쓣 以떎(Davies and Hawkins, 2020; Khan et al., 2018). 삉븳, MPO뒗 H2O2 chloride ions (Cl-)瑜 珥됰ℓ븯뿬 hypochlorous acid (HOCl)瑜 삎꽦떆耳 궛솕쟻 넀긽 諛 꽭룷 湲곕뒫 옣븷瑜 珥됱쭊븷 肉 븘땲씪 吏덈퀝쓽 諛쒕퀝 諛 留뚯꽦 뿼利앹쓣 쑀諛쒗븳떎怨 븣젮졇 엳떎(Daives and Hawkins, 2020). 궛솕쟻 뒪듃젅뒪(oxidative stress; OS)뒗 쇅遺쓽 뿬윭 옄洹뱀뿉 쓽빐 NADPH oxidase (NOX)濡쒕꽣 諛쒖깮맂 솢꽦궛냼醫(reactive oxygen species; ROS)뿉 쓽빐 깮꽦릺뼱 뿼利앸퓧 븘땲씪 떎뼇븳 吏덈퀝쓽 쑀諛쒓낵 諛젒븳 愿젴씠 엳뒗 寃껋쑝濡 븣젮졇 엳떎. OS瑜 諛쒖깮떆궎뒗 삉 떎瑜 슂냼 以 븯굹씤 吏덉냼醫(NO) 삉븳 怨쇱엵 깮궛맆 寃쎌슦 꽭룷쓽 궛솕 諛 넀긽뿉 愿뿬븯뿬 뿼利앹쓣 쑀諛쒗븯뒗 湲곗큹쟻씤 湲곗쟾씠 맂떎怨 븣젮졇 엳떎(Kim and Son, 2006). 蹂 떎뿕뿉꽌 EA1 닾뿬뒗 留뚯꽦 뿭瑜섏꽦 떇룄뿼뿉 쓽빐 利앷븳 삁以 MPO 닔移 諛 NADPH oxidase iNOS쓽 諛쒗쁽쓣 Normal援곌낵 鍮꾩듂븳 닔移섍퉴吏 쑀쓽쟻쑝濡 媛먯냼떆耳곗쑝硫, EA5 닾뿬 삉븳 MPO 닔移 諛 NADPH oxidase iNOS쓽 諛쒗쁽쓣 쑀쓽븯寃 媛먯냼떆耳곕떎(Table 1, Fig. 2). 씠윭븳 寃곌낵뒗 삤닔쑀-鍮덈옉옄 샎빀臾쇱씠 궛솕쟻 뒪듃젅뒪瑜 媛먯냼떆궡쑝濡쒖뜥 떇룄 젏留됱쓽 뿼利 셿솕뿉 愿뿬븷 寃껋씠씪 뙋떒맂떎.

NF-觀B뒗 씤媛꾩쓽 硫댁뿭 諛 뿼利 諛섏쓳뿉꽌 以묒슂븳 뿭븷쓣 븳떎怨 븣젮졇 엳뒗 쟾궗씤옄濡쒖뜥 二쇰줈 NF-觀B쓽 뼲젣젣씤 I觀B慣 寃고빀븯뿬 꽭룷吏덉뿉 議댁옱븯떎媛 뿬윭 蹂묒썝泥대뱾뿉 쓽빐 I觀B慣媛 씤궛솕릺硫댁꽌 빑 븞쑝濡 씠룞빐 DNA 寃고빀븯뿬 COX-2, iNOS 媛숈 源 쑀쟾옄쓽 諛쒗쁽쓣 옄洹뱁븿쑝濡쒖뜥 吏덈퀝쓣 쑀諛쒖떆궎硫, MAPK family 以 븯굹씤 p38 삉븳 NF-觀B쓽 솢꽦솕뿉 愿뿬븯뿬 NF-觀B쓽 뿼利 諛섏쓳쓣 룙뒗 寃껋쑝濡 븣젮졇 엳떎(Youn, 2012; Chien et al., 2018). 떇룄 議곗쭅 궡 뿼利 쟾궗씤옄 p-p38, NF-觀Bp65, p-I觀B慣쓽 諛쒗쁽쓣 솗씤븳 寃곌낵, EA1怨 EA5 닾뿬뒗 p-p38, NF-觀Bp65, p-I觀B慣쓽 諛쒗쁽쓣 쑀쓽쟻쑝濡 媛먯냼떆궓 寃껋쓣 솗씤븯떎(Fig. 3).

Cyclooxygenase (COX)뒗 븘씪궎룉궛(arachidonic acid)쓣 봽濡쒖뒪湲뵖(prostaglandin)쑝濡 蹂솚떆궎뒗 뿭븷쓣 븯硫, COX-1怨 COX-2쓽 삎깭濡 議댁옱븳떎(Vane et al., 1998). NF-觀B쓽 솢꽦솕濡 씤빐 諛쒗쁽릺뒗 COX-2뒗 뿼利 諛섏쓳뿉 愿뿬븯뒗 씤옄濡 븣젮졇 엳쑝硫, 뿼利 議곗쭅, 븙꽦醫낆뼇 벑뿉꽌 젙긽꽭룷뿉 鍮꾪빐 留롮 뼇쓽 봽濡쒖뒪湲뵖쓣 깮꽦븯뿬 꽭룷쓽 利앹떇쓣 룄슱 肉 븘땲씪 븫꽭룷쓽 꽦옣뿉 쟻빀븳 솚寃쎌쓣 젣怨듯븳떎(Cho et al., 2015). 諛섎㈃, COX-2 뼲젣젣濡 옒 븣젮졇 엳뒗 COX-1 쐞 諛 삁냼뙋뿉 議댁옱븯硫, 쐞궛쓣 議곗젅븷 肉 븘땲씪 쐞 젏留됱쓣 蹂댄샇븯뿬 냼솕湲곌퀎媛 젙긽쟻씤 湲곕뒫쓽 쑀吏瑜 룙뒗 以묒슂븳 뿭븷쓣 븳떎(Foye and Lemke, 2008; Bhagavan, 2002). 떇룄 議곗쭅 궡 arachidonic acid 愿젴 씤옄씤 COX-1 諛 COX-2쓽 諛쒗쁽쓣 솗씤븳 寃곌낵, EA1怨 EA5 닾뿬뒗 떇룄 議곗쭅 궡 COX-1 諛 COX-2쓽 諛쒗쁽쓣 쑀쓽쟻쑝濡 議곗젅븯떎(Fig. 4). 씠윭븳 寃곌낵뒗 삤닔쑀-鍮덈옉옄 샎빀臾쇱씠 NF-觀Bp65쓽 솢꽦솕瑜 뼲젣떆궡쑝濡쒖뜥 COX-1怨 COX-2쓽 諛쒗쁽쓣 議곗젅븯뒗 寃껋쑝濡 뙋떒맂떎.

留롮 뿰援щ 넻빐 NF-觀B뒗 tight junction (TJ) 떒諛깆쭏 諛 matrix metalloproteinases (MMPs)쓽 諛쒗쁽쓣 議곗젅븯뒗 寃껋쑝濡 븣젮議뚮떎(Shin and Choi, 2013). TJ 떒諛깆쭏 몴뵾 꽭룷痢듭쓽 꽭룷 媛꾧꺽뿉 쐞移섑븯뿬 꽭룷-꽭룷媛 닔遺, 쟾빐吏 벑쓽 씠룞쓣 議곗젅븯뒗 옣踰 떒諛깆쭏씠떎. TJ 떒諛깆쭏뿉뒗 Occludin, Claudin 벑씠 엳쑝硫(Kim and Jang, 2015), 뿭瑜섏꽦 떇룄뿼씠 쑀諛쒕릺硫 떇룄 젏留됱쓽 넀긽쑝濡 씤빐 寃고빀 議곗쭅뿉꽌쓽 TJ씠 媛먯냼븯뒗 寃껋쑝濡 븣젮졇 엳떎(Lee et al., 2020). 삉븳 MMPs뒗 떒諛깆쭏遺꾪빐슚냼濡쒖뜥 tissue inhibitor of metalloproteinases(TIMPs)뿉 쓽빐 議곗젅릺硫, TIMPs 븿猿 떊泥댁쓽 寃고빀 議곗쭅쓽 빆긽꽦쓣 쑀吏떆耳쒖<뒗 寃껋쑝濡 븣젮졇 엳쑝굹 MMPs/TIMPs쓽 洹좏삎씠 遺뺢눼릺硫 꽭룷쇅湲곗쭏쓽 遺꾪빐瑜 쑀룄븳떎(Lee et al., 2020). 蹂 떎뿕뿉꽌뒗 삤닔쑀-鍮덈옉옄 샎빀臾쇱쓣 닾뿬븯쓣 븣 tight junction 떒諛깆쭏쓽 諛쒗쁽씠 쑀쓽쟻쑝濡 利앷븯쑝硫, MMPs쓽 諛쒗쁽씠 Normal援곌낵 鍮꾩듂븳 닔以源뚯 媛먯냼븯쓣 肉 븘땲씪 TIMPs쓽 諛쒗쁽씠 쑀쓽쟻쑝濡 利앷븯떎. 씠윭븳 寃곌낵뒗 삤닔쑀-鍮덈옉옄 샎빀臾쇱씠 긽뵾꽭룷쓽 寃고빀 議곗쭅쓣 蹂댄샇븯쓬쓣 굹궦떎.

씠긽쓽 寃곌낵뒗 留뚯꽦 뿭瑜섏꽦 떇룄뿼뿉꽌 삤닔쑀-鍮덈옉옄 샎빀臾쇱 궛솕쟻 뒪듃젅뒪 議곗젅쓣 넻빐 NF-觀B 寃쎈줈瑜 뼲젣븯쓣 肉 븘땲씪 꽭룷쓽 寃고빀 議곗쭅뿉꽌 以묒슂븳 뿭븷쓣 븯뒗 tight junction怨 MMPs/TIMPs瑜 議곗젅븿쑝濡쒖뜥 떇룄 젏留됱쓽 넀긽쓣 셿솕븳 寃껋쑝濡 뙋떒릺硫, 씠윭븳 슚怨쇰뒗 삤닔쑀-鍮덈옉옄 1:1 샎빀臾(EA1)뿉꽌 뜑슧 쎇뼱굹寃 굹궗떎.

ACKNOWLEDGEMENT

This work has supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1I1A1A01064068 and No. 2017R1A2B2006858).

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

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