钙敏感受体在大鼠缺氧性肺动脉收缩和血管重构中的作用和分子机制

⬇䇋ҷⷕ ফ⧚䚼䮼 ᬊӊ᮹ᳳ ফ⧚㓪ো Ẕᶹֱᡸ ೑೑ᆊᆊ㞾㞾✊✊⾥⾥ᄺᄺ෎෎䞥䞥 ⬇⬇ 䇋䇋 кк (( 22 00 11 00 ⠜⠜ )) 䌘ࡽ㉏߿˖ Ѯ㉏䇈ᯢ˖ 䰘⊼䇈ᯢ˖ 乍Ⳃৡ⿄˖ ⬇ 䇋 Ҏ˖ ⬉䆱˖ ձᠬऩԡ˖ 䗮䆃ഄഔ˖ 䚂ᬓ㓪ⷕ˖ ऩԡ⬉䆱˖ ⬉ᄤ䚂ㆅ˖ ⬇᡹᮹ᳳ˖ 2010ᑈ3᳜6᮹ ೑ᆊ㞾✊⾥ᄺ෎䞥ྨਬӮ ᙼᙼ⦄⦄೼೼ϡϡ㛑㛑ẔẔᶹᶹֱֱᡸᡸ᭛᭛ḷḷ៪៪ᠧᠧॄॄ᭛᭛ḷḷˈˈ䇋䇋ḍḍ᥂᥂ҹҹϟϟϝϝϾϾℹℹ偸偸᪡᪡԰԰˖˖ 1)བབᵰᵰᙼᙼᰃᰃWord2000,word XP, word 2003៪៪ҹҹϞϞ⠜⠜ᴀᴀ⫼⫼᠋᠋ˈˈ䇋䇋ᡞᡞWord ᅣᅣⱘⱘᅝᅝܼܼᗻᗻ䆒䆒ЎЎ:"ЁЁ" ᮍᮍ⊩⊩: Word㦰㦰ऩऩ->ᎹᎹ݋݋->ᅣᅣ->ᅝᅝܼܼᗻᗻ->ᅝᅝܼܼ㑻㑻,䆒䆒㕂㕂ЎЎ"ЁЁ" (བབᵰᵰᙼᙼᰃᰃWord97⫼⫼᠋᠋ˈˈ㒻㒻㓁㓁ᠻᠻ㸠㸠ҹҹϟϟℹℹ偸偸) (བབᵰᵰᙼᙼᰃᰃ Office2007 ⫼⫼᠋᠋ˈˈ⚍⚍ߏߏ word ᎺᎺϞϞ㾦㾦"ᅝᅝܼܼ䄺䄺ਞਞ"໘໘"䗝䗝乍乍" ЁЁⱘⱘ"ਃਃ⫼⫼ℸℸݙݙᆍᆍ") 2)݇݇䯁䯁ᴀᴀ᭛᭛ḷḷˈˈ䞡䞡ᮄᮄᠧᠧᓔᓔᴀᴀ᭛᭛ḷḷ 3)⚍⚍ߏߏ"ਃਃ⫼⫼ᅣᅣ"ᣝᣝ䪂䪂ˈˈेेৃৃᓔᓔྟྟ฿฿ݭݭᴀᴀ᭛᭛ḷḷ៪៪ᠧᠧॄॄњњ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 2 义 ⠜ᴀ 1.003.565 ෎ᴀֵᙃ ykKr4oHP ⬇ 䇋 Ҏ ֵ ᙃ ྦྷ ৡ ᕤ䭓ᑚ ᗻ߿ ⬋ ߎ⫳ ᑈ᳜ 1945ᑈ 4᳜ ⇥ ᮣ ∝ᮣ ᄺ ԡ ᄺ຿ 㘠⿄ ᬭᥜ ↣ᑈᎹ԰ᯊ䯈˄᳜˅ 4 ⬉ 䆱 0451-86674548 ⬉ᄤ䚂ㆅ xucq45@126.com Ӵ ⳳ 0451-86674548 ೑߿៪ഄऎ Ё೑ Ͼ Ҏ 䗮 䆃 ഄ ഔ જᇨⒼᏖफቫऎֱع䏃 157ো Ꮉ ԰ ऩ ԡ જᇨⒼए⾥໻ᄺ /෎⸔एᄺ䰶⮙⧚⫳⧚ᬭⷨᅸ Џ 㽕 ⷨ お 乚 ඳ ᖗ㙠㔎㸔-ݡ☠⊼ᤳӸⱘথ⫳ᴎࠊ੠ֱᡸ ձ ᠬ ऩ ԡ ֵ ᙃ ৡ ⿄ જᇨⒼए⾥໻ᄺ 㘨 ㋏ Ҏ 䛁ᵒ ⬉ᄤ䚂ㆅ guosong@ems.hrbmu.edu.cn ⬉ 䆱 0451ˉ86669470 㔥キഄഔ http://61.158.20.195/ ড় ԰ ⷨ お ऩ ԡ ֵ ᙃ ऩ ԡ ৡ ⿄ >೼ℸᔩׂܹᬍ@ >೼ℸᔩׂܹᬍ@ 乍 Ⳃ ෎ ᴀ ֵ ᙃ 乍Ⳃৡ⿄ 䩭ᬣᛳফԧ೼໻哴㔎⇻ᗻ㚎ࡼ㛝ᬊ㓽੠㸔ㅵ䞡ᵘЁⱘ԰⫼੠ߚᄤᴎࠊ 䌘ࡽ㉏߿ 䴶Ϟ乍Ⳃ Ѯ ㉏ 䇈 ᯢ 䰘⊼䇈ᯢ ⬇䇋ҷⷕ H0203:ᖗ㙠㒚㚲/㸔ㅵ㒚㚲ᤳӸǃ ׂ໡ǃ䞡ᵘ੠ݡ⫳ H0109:㚎ᕾ⦃ঞ㚎㸔ㅵ⮒⮙ ෎ഄ㉏߿ ⾥ᡔ䚼੠咥啭∳ⳕ⫳⠽ए㥃Ꮉ⿟䞡⚍ᅲ偠ᅸ\䚼䮼ᓔᬒ ⷨおᑈ䰤 2011ᑈ 1᳜ ² 2013ᑈ 12᳜ ⷨおሲᗻ ෎⸔ⷨお ᨬ 㽕 (䰤䰤 400 ᄫᄫ)˖˖㚎ࡼ㛝催य़(PAH)ৃᇐ㟈েᖗ㙹໻ǃ㹄チ⫮㟇⅏ѵDŽPAH ⹂ߛᴎࠊᇮ᳾䯤ᯢˈ ໮䅸ЎϢ㚎ࡼ㛝ᬊ㓽੠䞡ᵘ᠔㟈ⱘ໪਼䰏࡯๲໻᳝݇DŽ䩭ᬣᛳফԧ˄CaSR˅ᰃ G㲟ⱑي㘨ফ ԧDŽᴀ䇒乬㒘佪⃵থ⦄ᖗ㙠㒘㒛᳝ CaSRᄬ೼ˈᑊ䆕ᅲᅗখϢᖗ㙠㔎㸔-ݡ☠⊼ᤳӸǃ㒚㚲ޟ ѵ੠ᖗ㙠㙹໻ⱘথ⫳DŽԚᰃ CˈaSRϢ PAHথ⫳থሩⱘ݇㋏ˈ䖘Ҟ೑ݙ໪ᇮ᮴᡹䘧DŽ೼ࠡᳳⷨ おЁ ៥ˈӀথ⦄໻哴㚎ࡼ㛝᳝ CaSRⱘࡳ㛑㸼䖒 ᑊˈ೼乘ᅲ偠Ё㾖ᆳࠄ㔎⇻ᯊ CaSR㸼䖒๲ࡴDŽ ៥Ӏ᥼⌟㔎⇻ᯊ㚎ࡼ㛝 CaSR 㸼䖒ৃ䇅ᇐ㚎㸔ㅵᬊ㓽੠䞡ᵘˈ䖭ৃ㛑ᰃ㔎⇻ᗻ㚎ࡼ㛝催य़ⱘ ϔϾᮄᴎࠊDŽЎ䆕ᅲ䖭ϔ؛䇈ˈ៥Ӏᇚ໡ࠊ໻哴ᗹᗻ੠᜶ᗻ㔎⇻῵ൟˈ䞛⫼ߚᄤ⫳⠽ᄺǃ⌕ ᓣ㒚㚲ҾㄝᡔᴃˈҢᭈԧ-㸔ㅵ⦃-㒚㚲ϝϾሖ⃵ˈ㾖ᆳ CaSR㸼䖒๲ࡴ៪⌏࣪ᇍ㚎ࡼ㛝ᓴ࡯ǃ 㸔ㅵ䞡ᵘⱘᕅડঞֵ݊োӴᇐ䗮䏃DŽᴀ䇒乬ᇚҢᮄⱘ㾚㾝䯤ᯢ PAHথ⫳ⱘߚᄤᴎࠊ ᑊˈЎ PAH ⱘ䰆⊏ᦤկᮄ䵊⚍DŽ ݇ 䬂 䆡(⫼ߚোߚᓔˈ᳔໮ 5Ͼ) 㔎⇻ᗻ㚎ࡼ㛝催य़˗䩭ᬣᛳফԧ˗㚎ࡼ㛝ᑇ⒥㙠˗㸔ㅵ䞡ᵘ˗໻ 哴 ೑ ᆊ 㞾 ✊ ⾥ ᄺ ෎ 䞥 ⬇ 䇋 к 20 10 ⠜ ㄀ 3 义 ⠜ ᴀ 1. 00 3. 56 5 乍 Ⳃ 㒘 Џ 㽕 খ Ϣ 㗙 ˄ ⊼ : 乍 Ⳃ 㒘 Џ 㽕 খ Ϣ 㗙 ϡ ࣙ ᣀ 乍 Ⳃ ⬇ 䇋 Ҏ ˈ ೑ ᆊ ᵄ ߎ 䴦 ᑈ ⾥ ᄺ ෎ 䞥 乍 Ⳃ ϡ ฿ ݭ ℸ ᷣ DŽ˅ 㓪 ো ྦྷ ৡ ߎ ⫳ ᑈ ᳜ ᗻ ߿ 㘠 ⿄ ᄺ ԡ ऩ ԡ ৡ ⿄ ⬉ 䆱 ⬉ ᄤ 䚂 ㆅ 乍 Ⳃ ߚ Ꮉ ↣ ᑈ Ꮉ ԰ ᯊ 䯈 ˄ ᳜ ˅ 1 ᐁ ⥝ ᜻ 19 76 -1 2- 19 ཇ 䆆 Ꮬ ⸩ ຿ જ ᇨ Ⓖ ए ⾥ ໻ ᄺ 04 51 -8 66 74 5 48 xy hu i7 7@ 12 6. co m ߚ ᄤ ⫳ ⠽ ᄺ 4 2 ᴢ 吓 ⦴ 19 77 -0 3- 08 ཇ 䆆 Ꮬ म ຿ જ ᇨ Ⓖ ए ⾥ ໻ ᄺ 04 51 -8 66 74 5 48 lih on gz hu 19 78 03 08 @ 12 6 .c om 㒚 㚲 ݙ 䩭 ⌟ ᅮ 4 3 ᴢ ܝ ӳ 19 70 -0 3- 05 ⬋ म ຿ ⫳ ⸩ ຿ જ ᇨ Ⓖ ए ⾥ ໻ ᄺ 04 51 -8 66 74 5 48 lig ua ng w ei 6@ so hu .c om 㚎 㸔 ㅵ 䞡 ᵘ ⱘ ֵ ো Ӵ ᇐ 6 4 䚱 䴭 䕝 19 84 -1 1- 18 ཇ ⸩ ຿ ⫳ ᄺ ຿ જ ᇨ Ⓖ ए ⾥ ໻ ᄺ 04 51 -8 66 74 5 48 ha oj in gh ui 11 @ 12 6. co m 㙠 ᓴ ࡯ Ẕ ⌟ 6 5 ⥟ ⃷ ➩ 19 75 -1 2- 22 ཇ Џ ⊏ ए Ꮬ ⸩ ຿ જ ᇨ Ⓖ ए ⾥ ໻ ᄺ 04 51 -8 66 74 5 48 w xy ly f1 1@ 16 3. co m ܡ ⭿ 㒘 ࣪ 3 6 ᄭ ع 19 75 -8 -1 ཇ म ຿ ⫳ ⸩ ຿ જ ᇨ Ⓖ ए ⾥ ໻ ᄺ 04 51 -8 66 74 5 48 m dj su nj ia n@ 12 6. co m 㒚 㚲 ਼ ᳳ 6 7 ᄨ ޵ ࿳ 19 85 -7 -2 8 ཇ ⸩ ຿ ⫳ ᄺ ຿ જ ᇨ Ⓖ ए ⾥ ໻ ᄺ 04 51 -8 66 74 5 48 kf j_ 85 07 28 @ si na .c om ⫳ ࣪ ⌟ ᅮ 4 8 䌒 ⋾ Б 19 84 -2 -8 ཇ ⸩ ຿ ⫳ ᄺ ຿ જ ᇨ Ⓖ ए ⾥ ໻ ᄺ 04 51 -8 66 74 5 48 jia ho ng li@ 12 6. co m ῵ ൟ ࠊ ໛ 6 9 ਈ म 19 78 -1 0- 15 ཇ ࡽ ᬭ ⸩ ຿ જ ᇨ Ⓖ ए ⾥ ໻ ᄺ 04 51 -8 66 74 5 48 w ub ow @ 16 3. co m ߚ ᄤ ⫳ ⠽ ᄺ 4 ᘏ Ҏ ᭄ 催 㑻 Ё 㑻 ߱ 㑻 म ຿ ৢ म ຿ ⫳ ⸩ ຿ ⫳ 1 0 1 3 1 2 3 䇈 ᯢ : 催 㑻 ǃ Ё 㑻 ǃ ߱ 㑻 ǃ म ຿ ৢ ǃ म ຿ ⫳ ǃ ⸩ ຿ ⫳ Ҏ ਬ ᭄ ⬅ ⬇ 䇋 Ҏ 䋳 䋷 ฿ ᡹ ˄ ৿ ⬇ 䇋 Ҏ ˅ˈ ᘏ Ҏ ᭄ ⬅ ৘ ߚ 乍 㞾 ࡼ ࡴ ੠ ѻ ⫳ DŽ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 4 义 ⠜ᴀ 1.003.565 㒣䌍⬇䇋㸼 ˄䞥乱ऩԡ˖ϛܗ˅ ⾥Ⳃ ⬇䇋㒣䌍 ໛⊼˄䅵ㅫձ᥂Ϣ䇈ᯢ˅ ϔ..ⷨお㒣䌍 29.6400 1.⾥ⷨϮࡵ䌍 7.2000 ˄1˅⌟䆩/䅵ㅫ/ߚᵤ䌍 2.2000 mRNA⌟ᑣǃᓩ⠽ড়៤ǃ೒ڣߚᵤǃ⌕ᓣ㒚㚲Ҿǃ⬉䬰Ẕᶹ䌍ㄝ ˄2˅㛑⑤/ࡼ࡯䌍 ˄3˅Ӯ䆂䌍/Ꮒᮙ䌍 1.9000 ᄺᴃӮ䆂 0.4h4Ҏ⃵,⾥ⷨ䇗ⷨᏂᮙ䌍 0.3 ˄4˅ߎ⠜⠽/᭛⤂/ֵᙃӴ᪁䌍 2.3000 ೑ݙ໪ᳳߞ䆎᭛থ㸼䌍 1.5,᭛⤂䌘᭭䌍 0.3,ㄨ䕽䆘ᅵ䌍 0.3,ֵᙃӴ᪁䌍 0.3 ˄5˅݊Ҫ 0.8000 ϡৃ乘㾕䌍 2.ᅲ偠ᴤ᭭䌍 20.7000 ˄1˅ॳᴤ᭭/䆩ࠖ/㥃ક䌁㕂䌍 18.5000 RNA䆩ࠖⲦǃRT-PCR䆩ࠖǃ৘⾡ᡫԧǃ࣪ᄺ䆩ࠖǃ PCRᓩ⠽ⱘ䆒䅵ǃ৘⾡㗫ᴤ ˄2˅݊Ҫ 2.2000 ᷛޚᅲ偠ࡼ⠽䌁фঞ但ݏ 3.Ҿ఼䆒໛䌍 0.9400 ˄1˅䌁㕂 0.9400 ∂⇨থ⫳఼ ˄2˅䆩ࠊ 4.ᅲ偠ᅸᬍ㺙䌍 0.8000 5.ण԰䌍 Ѡ..೑䰙ড়԰ϢѸ⌕䌍 3.8000 1.乍Ⳃ㒘៤ਬߎ೑ড়԰Ѹ⌕ 2.4000 খࡴ೑䰙Ӯ䆂 1Ҏ⃵ 2.๗໪ϧᆊᴹढড়԰Ѹ⌕ 1.4000 ๗໪ϧᆊⷁᳳᴹढড়԰Ѹ⌕೑䰙ᮙ䌍੠⫳⌏䌍 ϝ..ࢇࡵ䌍 3.8000 খࡴ䇒乬ⱘⷨお⫳੠म຿ৢⱘࢇࡵ੠⫳⌏㸹ࡽ䌍 ಯ..ㅵ⧚䌍 1.9600 ᣝ෎䞥ྨ㾘ᅮ˖㒣䌍 5ˁЎㅵ⧚䌍 ড় 䅵 39.2000 Ϣᴀ乍ⳂⳌ݇ⱘ ݊Ҫ㒣䌍ᴹ⑤ ೑ᆊ݊Ҫ䅵ߦ䌘ࡽ㒣䌍 ݊Ҫ㒣䌍䌘ࡽ˄৿䚼䮼ऍ䜡˅ ݊Ҫ㒣䌍ᴹ⑤ড়䅵 0.0000 ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 5 义 ᶹⳟ᡹ਞℷ᭛᪄ݭᦤ㒆 ᡹ਞℷ᭛ ďྡྷĐोົྦྷ࡬ူཙࡎઝఘ 1. ົંԅोົྦྷ࡬ 㚎ࡼ㛝催य़(pulmonary arterial hypertensionˈPAH)ᰃϡৠ⮙಴ᇐ㟈ⱘҹ㚎ࡼ㛝य़࡯੠㚎㸔 ㅵ䰏࡯छ催Ў⡍⚍ⱘϔ㒘⮒⮙៪Јᑞ㓐ড়ᕕˈথথ⮙⥛੠⅏ѵ⥛ᕜ催ˈ݊থ⮙ᴎࠊЏ㽕Ў㸔ㅵᬊ㓽ǃ 㸔ㅵ䞡ᵘ੠㸔ᷧᔶ៤Ǐ1ˈ2ǐDŽབᵰPAHϡࡴ⊏⭫ˈ᳔㒜ᇐ㟈েᖗ㹄チǃᆍ䞣䋳㥋๲ࡴⳈ㟇⅏ѵǏ3ǐDŽ䗮 ᐌ㚎ࡼ㛝催य़ⱘ߸ᅮᷛޚЎ˖ᑇഛ㚎ࡼ㛝य़࡯೼䴭ᙃ⢊ᗕϟ>25 mm Hgˈ䖤ࡼ⢊ᗕϟ>30 mm HgDŽ PAH᳝໮⾡ߚ㉏ᮍ⊩DŽ1998ᑈࠡ ҙˈߚЎॳথᗻ㚎ࡼ㛝催य़(PPH)੠㒻থᗻ㚎ࡼ㛝催य़(SPH)ϸ໻ ㉏DŽ2003ᑈ㄀3ሞ࿕ሐᮃPAHӮ䆂ˈᇚPAH䖯ϔℹߚЎ˖ķ ⡍থᗻPAH(IPAH)˗ĸ ᆊᮣᗻPAH(FPAH)˗ Ĺ 㦋ᕫᗻPAH(APAH)˗ĺ Ϣ䞡㽕䴭㛝៪↯㒚㸔ㅵⳌ݇ⱘPAH˗Ļᮄ⫳ܓᣕ㓁ᗻPAH(PPHN)DŽḍ᥂㕢೑ ⮒᥻Ёᖗⱘ䌘᭭ˈ৘৘㉏ൟPAHᙷ⮙⥛Ꮖ䍙䖛3O̚5OҎˋ100ϛҎǏ4ˈ5ǐDŽ 䆌໮᜶ᗻ੐਌㋏㒳⮒⮙៪㔎⇻ৃᓩ䍋Ԣ⇻ᗻPAH 1˖˅䰏าᗻ㚎⮒⮙˖᜶ᗻ䰏าᗻ㚎⮒⮙(COPD)ǃ ಞ⊵ᗻ㑸㓈࣪/ᬃ⇨ㅵᠽᓴㄝ˗2˅䯈䋼ᗻ㚎⮙˖⡍থᗻ䯈䋼ᗻ㚎♢ㄝ˗3˅㚎⊵ᤶ⇨ϡ䎇˖㙹㚪䗮⇨ ϡ㡃㓐ড়⮛⼲㒣㙠㙝⮙ㄝ˗˄4˅ⴵ⳴䱰⹡ᗻ੐਌˖ⴵ⳴੐਌᱖ذㄝ˗˄5˅Йሙ催ቅ៪催ॳ˗˄6˅ থ㚆ᓖᐌ/ᮄ⫳ܓ㚎⮒ᙷǏ6ǐDŽ PAHⱘথ⫳ᴎࠊ໡ᴖDŽ⡍থᗻ੠ᆊᮣᗻPAHЏ㽕ϢBMPR2ㄝ෎಴さব᳝݇Ǐ7ǐDŽӫ᠔਼ⶹˈ㚎㸔ㅵ ᬊ㓽ᰃPAHⱘᮽᳳ㒘ߚˈ⬅㒚㚲ݙ䩭๲ࡴ㾺থˈֵোӴᇐ䗮䏃Џ㽕ࣙᣀPKCǃRho▔䝊੠⦃⻋䝌㝎㣋 ˄cAMP੠cGMP˅ˈ䩭ᑧ᪡㒉ᗻ䩭䗮䘧੠⬉य़䮼᥻ᗻ䪒䗮䘧˄㾕೒1˅Ǐ8ǐDŽ ೒1 㚎ࡼ㛝ᑇ⒥㙠㒚㚲ⱘ䩭〇ᗕ䇗㡖ᴎࠊ ೼催㚎㸔⌕ǃԢ⇻ǃ↦⠽ㄝ⮙⧚ᴵӊϟˈ㸔ㅵݙⲂ㒚㚲ǃᑇ⒥㙠㒚㚲ǃ៤㑸㓈㒚㚲ҹঞ㸔ᇣᵓ੠ ऩḌᎼీ㒚㚲ߚ⊠㸔ㅵ⌏ᗻҟ䋼ⱘᑇ㸵༅䇗ˈৃ֗䖯㸔ㅵᬊ㓽ǃ㸔ㅵ䞡ᵘҹঞ㸔ᷧᔶ៤˄೒2˅Ǐ1ǐDŽ PAHথ⫳ⱘߚᄤᴎࠊϢ㸔ㅵ㟦ᓴ੠ᬊ㓽಴ᄤ༅㸵ǃ偼ᔶᗕথ⫳㲟ⱑIIൟফԧ˄BMPRII˅ֵো䗮䏃 ▔⌏ǃᔍᗻ㲟ⱑ䝊⌏࣪ǃ䪒䗮䘧ࡳ㛑䱰⹡ǃ㒓㉦ԧᓖᐌǃⶀᯊফԧ⬉ԡ䩭䗮䘧˄TRPC˅▔⌏ǃAMPK ▔⌏㸔ㅵຕ֗♢ডᑨㄝ᳝݇˄೒3˅Ǐ9ǐDŽ ⇨ԧֵোߚᄤNOǃCOǃH2Sঞ݊䇗㡖ㄝᏆ៤ЎPAHⱘⷨお⛁⚍Ǐ7ǐˈᴰ ݯֱㄝᏆᓔሩњ㋏߫ⷨおDŽNotch3 ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 6 义 ֵোӴᇐ䗨ᕘ೼֗䖯PAHথሩЁ԰⫼ᓔྟফࠄҎӀ䞡㾚˄ Li XD et al, nature medicine 2009; 15: 1289- 1299˅. 䖥ᑈᴹˈજए໻ᴅ໻ኁㄝᇍ15-HETE೼Ԣ⇻ᗻPAHⱘ԰⫼੠ᴎࠊ䖯㸠њ㋏㒳ⷨおǏ10ˈ11ǐDŽ ೒2 ৘⾡㒚㚲೼㚎ࡼ㛝催य़ᯊ㸔ㅵ䞡ᵘЁ԰⫼ ೒3 㚎ࡼ㛝催य़˄PAH˅ߚᄤথ⫳ᴎࠊ ḍ᥂PAHথ⫳ⱘߚᄤᴎࠊˈҎӀ䞛⫼ᔍᗻ㲟ⱑ䝊ᡥࠊࠖǃKvᓔᬒࠖǃTRP䗮䘧ᡥࠊࠖǃ䋳ᗻ⫳ᄬ ㋴ǃҪ∔㉏㥃⠽ǃPPARȖ ▔ࡼࠖǃ৘⾡⫳䭓಴ᄤফԧⱘᡥࠊࠖǃ㚒Ϟ㝎傧䋼㋴ǃRho ▔䝊ᡥࠊࠖǃ ݙⲂ⼪㒚㚲ǃ⦃ᄶ䳝㋴Aㄝ⊏⭫Ǐ9ǐDŽ ೑ݙ೼ PAHⱘⷨおᰃᮍ݈᳾㡒DŽ ヨ㗙ҹĀ㚎ࡼ㛝催य़āЎẔ㋶Џ乬䆡Ẕ㋶೑ᆊ㞾✊⾥ᄺ෎䞥ྨ 㔥キˈ㒧ᵰᰒ⼎˖᳔䖥 5ᑈݙᕫࠄ೑ᆊ㞾✊⾥ᄺ෎䞥ྨ䌘ࡽⱘ᳝݇Ā㚎ࡼ㛝催य़āⷨお乍Ⳃড়䅵 37 乍ˈਜ䗤ᑈ๲ࡴ䍟࢓˄05ᑈ 3乍ˈ06ᑈ 4乍ˈ07ᑈ 7乍ˈ08ᑈ 9乍ˈ09ᑈ 14乍˅ˈⷨおݙᆍЏ㽕 ⍝ঞϞ䗄ᦤࠄⱘ᳝݇಴㋴Ǐ7-11ǐDŽ Ԛᰃ 㚎ˈࡼ㛝催य़ⱘⷨお㱑᳝100໮ᑈⱘग़৆ˈ݊ থ⮙ᴎࠊ㟇Ҟᇮ᳾䯤ᯢǏ1ˈ7ˈ12ǐDŽሑㅵ⦄ҷ࣪ⱘ ⊏⭫ᯢᰒᬍ୘њPAHᙷ㗙ⱘ⫳⧚ࡳ㛑੠ᓊ䭓њᇓੑˈԚ݊⅏ѵ⥛ҡ催䖒50%Ǐ13ǐDŽ䖭ህ㽕∖ҎӀҢ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 7 义 ᮄⱘ㾚㾝ˈ䖯ϔℹ䯤ᯢ㚎ࡼ㛝催य़ⱘথ⫳ᴎࠊˈҹ֓Ў᳝݊ᬜ䰆⊏ᦤկᮄ䵊⚍DŽ 䩭ᬣᛳফԧ(calcium-sensing receptor, CaSR)ᰃG 㲟ⱑ㗺㘨ফԧⱘCᆊᮣ៤ਬDŽ1993 ᑈΤBrown et al 佪⃵⬅⠯⬆⢊ᮕ㝎ܟ䱚ߎCaSRDŽCaSR⬅⇼෎㚲໪ඳ˄ECD ǃ˅7Ͼ䎼㝰㶎ᮟⱘ䎼㝰ඳ˄TCD˅੠ 㚲ݙ㕻෎ሒ䚼᠔㒘៤˄㾕೒4 DŽ˅CaSRЏ㽕ߚᏗ೼খϢ䩭〇ᗕ䇗㡖ⱘ⬆⢊ᮕ㝎ǃ㚒㙴䘧ǃ偼㒘㒛੠㚒 㒘㒛ҹঞ݊Ҫ㒚㚲˄՟བˈЁᵶ੠໪਼⼲㒣ǃ㙱㛣ˈ㸔㒚㚲ǃ㛄㝎ȕ 㒚㚲ㄝ˅DŽ݊ࡳ㛑Џ㽕ᰃ㓈ᣕ Ca 2+੠݊Ҫ䞥ሲ⾏ᄤ〇ᗕ ᇮˈৃ䇗㡖㒚㚲๲Ⅺǃߚ࣪ǃ⾏ᄤ䗮䘧ᓔਃǃ▔㋴ߚ⊠ㄝDŽ㒚㚲໪Ca2ˇᰃCaSR ⱘЏ㽕䜡ԧˈMg2ˇǃGd3ˇǃᮄ䳝㋴ǃ㊒㛎˄spermine˅ㄝ໮Ӌ䰇⾏ᄤѺᰃCaSRⱘ▔ࡼࠖ[14]DŽ ೒ 4 䩭ᬣᛳফԧᴎᵘ⼎ᛣ೒ ᖗ㸔ㅵ乚ඳ CaSRⱘⷨおᓔሩ䕗ᰮDŽ乍Ⳃ⬇䇋ҎϢࡴᣓ໻ Wang Ruiᬭᥜড়԰ˈ佪⃵೼೑䰙Ϟ䆕 ᯢњ໻哴ᖗ㙠᳝ CaSR 㸼䖒˄Wang R, Xu CQ, Zhao WM, et al. Calcium and polyamine regulated calcium-sensing receptors in cardiac tissues. Eur. J. Biochem. 2003ˈ270˖ 2680±2688 ) [15]DŽ䖘Ҟˈ䆹᭛㹿 SCIᓩ⫼ 31⃵DŽ 2006ᑈˈTfelt-Hansen ㄝҎ᡹ਞˈCaSR೼ᮄ⫳໻哴ᖗᅸ㙠㒚㚲г᳝ࡳ㛑ᗻ㸼䖒 [16]DŽ䖥ᑈᴹˈ ݊Ҫᅲ偠ᇣ㒘гᦤկњϔѯ䆕᥂ˈ㸼ᯢ CaSR೼Џࡼ㛝ㄝ㸔ㅵⱘݙⲂ㒚㚲੠ᑇ⒥㙠᳝ࡳ㛑ᗻ㸼䖒 [17ˉ 18]DŽ᳔䖥ˈMasih-ul Alam ㄝ䆕ᅲᗻ㚒㹄ᯊⱘ㸔ㅵ䩭࣪Ԉ᳝㸔ㅵᑇ⒥㙠㒚㚲ࡳ㛑ᗻ䩭ᬣᛳফԧⱘ϶ ༅Ǐ19ǐDŽ 2004 ᑈҹᴹˈ乍Ⳃ⬇䇋Ҏ㦋ᕫњ 3 乍೑ᆊ㞾✊⾥ᄺ෎䞥䌘ࡽ˖1˅lj໻哴ᖗ㙠㒚㚲䩭ᬣᛳফԧ ⱘ⫳⠽ᄺ⌏ᗻঞ݊೼ᖗ㙠㔎㸔/ݡ☠⊼ᤳӸЁⱘ԰⫼NJ˄30370577ˈ2004-2006˅˗2˅໻哴ᖗ㙠໮㛎 ҷ䇶㾘ᕟ੠"ঠߗࠥ"԰⫼ᴎࠊⱘⷨおNJ˄30470688ˈ2005-2007˅˗˄3˅lj䩭ᬣᛳফԧᇍࡼ㛝㉹ḋ ⹀࣪໻哴ᗹᗻᖗ㙠ṫ⅏ᯧᛳᗻⱘᕅડ੠ֱᡸⷨおNJ˄ 30871012ˈ2009-2011 DŽ˅ ೼Ϟ䗄乍Ⳃⱘ䌘ࡽϟ ᴀˈ䇒乬㒘佪⃵থ⦄ (˖1)CaSR೼໻哴ᖗ㙠㒘㒛Ёᄬ೼ঞϡৠ哴啘ⱘ㸼䖒㾘 ᕟ˗˄ 2˅CaSR▔⌏䗮䖛G㲟ⱑ-PLC-IP3䗮䏃ᓩ䍋[Ca2+]i๲ࡴˈᇐ㟈䩭䍙䕑˗˄ 3˅CaSR೼ᖗ㙠㔎㸔-ݡ ☠⊼ᯊⱘ㸼䖒㾘ᕟˈৃ 䗮䖛㒓㉦ԧ䗮䏃ǃFas⅏ѵফԧ䗮䏃੠ݙ䋼㔥ᑨ▔䗮䏃䇅ᇐᖗ㙠㒚㚲ޟѵ˗˄ 4˅ PKCİ ҟᇐCaSR⌏ᗻᬍবˈখϢњ㔎㸔ৢ䗖ᑨ˗˄ 5˅CaSR䗮䖛⼲㒣䩭䇗⻋䝌䝊খϢAngII䇅ᇐⱘ໻哴 ᖗ㙠㙹໻˗˄ 6 C˅aSR㸼䖒๲ࡴৃՓࡼ㛝㉹ḋ⹀࣪໻哴ᇍᖗ㙠ṫ⅏ⱘᬣᛳᗻ๲ࡴǏ15ˈ20-28ǐDŽ䖘Ҟ Ꮖˈথ 㸼Ⳍ݇䆎᭛30ԭ㆛ˈ݊ЁSCIᬊᔩ12㆛˄䆺㾕ϟ䴶ⷨお෎⸔˅DŽ೑ᆊ㞾✊෎䞥乍Ⳃlj໻哴ᖗ㙠㒚㚲䩭 ᬣᛳফԧⱘ⫳⠽ᄺ⌏ᗻঞ݊೼ᖗ㙠㔎㸔/ݡ☠⊼ᤳӸЁⱘ԰⫼NJᏆ㦋2008ᑈ咥啭∳ⳕᬓᑰ㞾✊⾥ᄺѠ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 8 义 ㄝ༪˄⬇䇋Ҏᥦৡ㄀ϔ˅DŽ CaSRⳂࠡᏆ៤Ў೑䰙ⱘⷨお⛁⚍ˈ೼៥೑гᓔྟᕫࠄ݇⊼DŽ䖘ҞЎℶˈ೑ᆊ㞾✊෎䞥ྨ䌘ࡽ᳝ ݇CaSRⱘⷨお乍Ⳃ݅9乍˄㾕ϟ㸼˅˖ ሑㅵ೑ݙ໪ᄺ㗙೼ᖗ㸔ㅵ㋏㒳ⱘ䩭ᬣᛳফԧ˄CaSR˅ᮍ䴶ᓔሩњϔѯⷨおˈԚᰃ㚎ࡼ㛝ᑇ⒥㙠 㒚㚲᳝᮴ CaSRⱘࡳ㛑㸼䖒ঞ݊⮙⧚⫳⧚ᛣНˈ䖘Ҟ᳾㾕᳝ PubMedᬊᔩ䆎᭛থ㸼DŽ 2010.3.6ˈヨ㗙೼㔥ϞẔ㋶њ PubMedDŽ೼Ā乬Ⳃ/ᨬ㽕ā㣗⭈ݙˈҹĀ㚎ࡼ㛝催य़āǃĀ㚎ࡼ㛝 ᑇ⒥㙠āǃĀ㚎ࡼ㛝ᑇ⒥㙠㒚㚲āǃĀ䩭ᬣᛳফԧāЎẔ㋶䆡ˈߚ߿Ẕߎ 8106ǃ1314ǃ472ǃ1274 ㆛䆎 ᭛ˈԚᰃᇚĀ䩭ᬣᛳফԧāϢ݊ҪẔ㋶䆡㘨ড়Ẕ㋶ˈ߭Ẕ㋶㒧ᵰഛЎĀ0ā˄ 㾕ϟ㸼 DŽ˅ Mo-Jun Linㄝ㾖ᆳࠄˈ᜶ᗻ㔎⇻ᯊⶀᯊফԧ⬉ԡ(TRPC) ෎಴䋳䋷㓪ⷕⱘ䩭ᑧ᪡㒉ᗻ䰇⾏ᄤ䗮䘧 ੠ফԧ᪡㒉ᗻ䰇⾏ᄤ䗮䘧೼㚎ࡼ㛝ᑇ⒥㙠㸼䖒Ϟ䇗ˈᑊ䅸Ў䖭ৃ㛑ᰃ㔎⇻ᗻPAHⱘϔϾᮄᴎࠊǏ29ǐDŽ 䡈ѢCaSR᱂䘡೼ᴎԧ৘㋏㒳ǃ఼ᅬǃ㒘㒛੠㒚㚲Ё᳝㸼䖒ˈ㗠ϨCaSRᓩ䍋㒚㚲ݙ䩭छ催ⱘᴎࠊ гᰃ䗮䖛䩭ᑧ᪡㒉ᗻ䩭䗮䘧˄SOCC˅੠ফԧ᪡㒉ᗻ䩭䗮䘧˄ROCC˅ˈ಴ℸˈ៥៥Ӏ᥼⌟CaSR೼㚎ࡼ㛝 ᑇ⒥㙠㒚㚲᳝ࡳ㛑㸼䖒ˈᑊৃ㛑খϢ㔎⇻ᗻ㚎ࡼ㛝催य़ⱘথ⫳DŽ䖭⾡؛䇈Ꮖ೼乘ᅲ偠Ёᕫࠄњ߱ℹ 䆕ᅲ˄䆺㾕Ꮉ԰෎⸔˅˖ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 9 义 ៥Ӏⷨおᇣ㒘੠ৠ⌢एᄺ䰶㚵⏙ढⷨおᇣ㒘೼೑ݙৠᯊᓔሩњ㚎ࡼ㛝 CaSR ⱘⷨおˈᑊߚ߿䆕ᯢ 㚎ࡼ㛝᳝ CaSRⱘ㸼䖒 㚵˖⏙ढᬭᥜⱘम຿ⷨお⫳㔫টḍথ㸼њҪⱘᄺԡ䆎᭛Āᮄⱘ㒚㚲໪䩭ᛳফᴎ ࠊ೼㔎⇻ᓩ䍋㚎ࡼ㛝ᑇ⒥㙠㒚㚲㚲Ḽ䩭⾏ᄤ⌧ᑺব࣪Ёⱘ԰⫼ā˄ 2009.5.23˅˗ ᴀҎⱘम຿ⷨお⫳ᴢ ܝӳ೼lj㄀ϗሞ⍋ኵϸኌᖗ㸔ㅵ⾥ᄺⷨ䅼ӮNJ˄ 2009.8.14-17,ᯚᯢ˅г԰њĀ䩭ᬣᛳফԧ೼໻哴㚎 ࡼ㛝ᑇ⒥㙠㒚㚲ⱘࡳ㛑ᗻ㸼䖒āⱘᄺᴃ᡹ਞ˄᭛〓 KM222˅ˈ Ⳃࠡ㣅᭛〓ӊᏆᡩߎǏ30ǐDŽ ᜶ᗻ੐਌㋏㒳⮒⮙៪㔎⇻ᚙމ೼ЈᑞϞᕜᐌ㾕DŽ՟བˈ᜶ᗻ䰏าᗻ㚎⮒⮙(COPD)೼៥೑ⱘ࣫ᮍ ഄऎ˄ᇸ݊ݰᴥ˅कߚᐌ㾕DŽ᜶ᗻᬃ⇨ㅵ♢ė䰏าᗻ㚎⇨㚓ė㔎⇻ᗻ㚎ࡼ㛝催य़ėেᖗ㙹໻ėেᖗ 㹄チˈ޴Т៤њ⮒⮙থ⫳থሩⱘ㾘ᕟDŽ㔎⇻ᗻPAHⱘথሩˈᇍ⮒⮙ⱘ䖯ሩ䍋ⴔ᥼⊶ࡽ╰ⱘ԰⫼DŽ᜶䰏 㚎(COPD)ϡҙ㒭ᙷ㗙ᏺᴹњᎼ໻ⱘ⮯㢺ˈг㒭ᆊᒁ੠⼒Ӯᏺᴹњ≝䞡ⱘ㒣⌢䋳ᢙDŽ៥៥Ӏⱘⷨおᇚ䖯 ϔℹᧁ⼎㔎⇻ᗻ㚎ࡼ㛝催य़ⱘথ⫳ᴎࠊˈЎ᳝݊ᬜ䰆⊏ᦤկᮄ⧚䆎੠㥃⠽ᮄ䵊⚍DŽ খ㗗᭛⤂ 1. 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Wang LN, Wang C, Lin Y, Xi YH, Zhang WH, Zhao YJ, Li HZ, Tian Y, Lv YJ, Yang BF, Xu CQ˄ ˅.Involvement of calcium-sensing receptor in cardiac hypertrophy-induced by angiotensinII through calcineurin ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 11 义 pathway in cultured neonatal rat cardiomyocytes. Biochemical and Biophysical Research Communications 2008,369(2):584-589 28. Guo J, Li HZ, Zhang WH, Wang LC, Wang LN, Zhang L, Li GW, Li HX, Yang, BFˈWu LY, Wang R, Xu CQ˄ ˅. Increased expression of calcium-sensing receptors induced by ox-LDL amplifies apoptosis of cardiomyocytes during simulated ischaemia̢reperfusion. Clinical and Experimental Pharmacology and Physiology (2010) 37, e128̢e135 29. Mo-Jun Lin, George P.H. Leung, Wei-Min Zhang, et al. Chronic Hypoxia̢Induced Upregulation of Store-Operated and Receptor-Operated Ca 2+ Channels in Pulmonary Arterial Smooth Muscle Cells ̢ A Novel Mechanism of Hypoxic Pulmonary Hypertension. Circ Res. 2004;95:496-505 30. Li GW, Wang QS, Hao JH, Xing WJ, Guo J, Li HZ, Bai SZ, Li HX, Yang BF, Wu LY, Wang R and Xu CQ˄ ˅. Functional expression of the extracellular calcium-sensing receptor in rat pulmonary artery smooth muscle cells. AM J PHYSIOL-LUNG C (in submit) 2. ົંԅཙࡎઝఘcཙࡎંγ,ྻރથࠓࢅԅڑߏࢳ༰ูඕ ཙࡎઝఘ ˄1˅໻哴㚎ࡼ㛝ᑇ⒥㙠䩭ᬣᛳফԧⱘߚᏗǃ㸼䖒੠ࡳ㛑˄Ꮖ෎ᴀᅠ៤˅ 䞛⫼㒘㒛࣪ᄺ੠ܡ⭿㤻ܝᡔᴃ ⹂ˈᅮ CaSR೼໻哴㚎ࡼ㛝ᑇ⒥㙠੠㒚㚲ⱘߚᏗ⡍⚍ 䞛˗⫼ PR-PCR ੠ Western Blot ᡔᴃˈ㾖ᆳ CaSR೼໻哴㚎ࡼ㛝ᑇ⒥㙠㒘㒛੠㒚㚲ⱘ㸼䖒ᚙމ˗䞛⫼▔ܝ݅㘮⛺ᡔ ᴃ ⹂ˈᅮ CaSR▔⌏ᓩ䍋㚎ࡼ㛝ᑇ⒥㙠㒚㚲[Ca2+]i๲ࡴⱘᴎࠊ੠䗨ᕘ 䞛˗⫼㸔ㅵ⦃Ẕ⌟ᡔᴃ 㾖ˈᆳ CaSR ᇍ㚎ࡼ㛝ᑇ⒥㙠ᓴ࡯ⱘᕅડDŽᜢᆚߚ㒘ˈᑨ⫼৘⦃㡖▔ࡼࠖ៪ᡥࠊࠖˈҹ⹂ֱ㒧䆎ৃ䴴˄ϟ䆺 DŽ˅ ˄2˅㔎⇻ᯊ໻哴㚎ࡼ㛝ᑇ⒥㙠䩭ᬣᛳফԧ㸼䖒ⱘব࣪ঞ݊ᇍ㸔ㅵᬊ㓽੠䞡ᵘⱘᕅડ 䞛⫼໻哴ᭈԧ㔎⇻῵ൟ੠㒚㚲㔎⇻῵ൟ԰Ўⷨおᇍ䈵 䞛ˈ⫼Ϟ䗄৘⾡ᅲ偠ᡔᴃ 㾖ˈᆳᗹ᜶ᗻ㔎 ⇻˄㔎⇻ϡৠᯊ䯈˅ᇍ໻哴㚎ࡼ㛝ᑇ⒥㙠ⱘ CaSR㸼䖒ǃ㙠ᓴ࡯ǃ㒘㒛䞡ᵘ˄㒚㚲๲Ⅺ੠㒚㚲ޟѵ˅ ⱘᕅડ ᧁˈ⼎ CaSR㸼䖒๲ࡴ੠▔⌏ᇍ㚎㸔ㅵᬊ㓽ǃ㸔ㅵ䞡ᵘⱘᕅડ੠ֵোӴᇐ䗨ᕘ ҹˈ֓䯤ᯢ CaSR ೼㔎⇻ᗻ㚎ࡼ㛝催य़Ёⱘ԰⫼੠ߚᄤᴎࠊDŽCaSR 㸼䖒ǃ㙠ᓴ࡯੠[Ca2+]i⌟ᅮⱘᮍ⊩ৠϞ˗⫼㒚㚲๲ Ⅺ੠㒚㚲ޟѵ԰Ўড᯴㸔ㅵ䞡ᵘⱘᣛᷛˈ㾖ᆳᔶᗕᄺǃ๲Ⅺ˄ޟѵ˅⥛ǃⳌᑨֵোӴᇐ䗮䏃݇䬂ߚ ᄤ㸼䖒ⱘব࣪DŽ݋ԧⱘⷨおݙᆍǃᮍ⊩੠䏃㒓ˈ䆺㾕ϟ䴶ⱘⷨおᮍḜDŽ ཙࡎંγ ˄1˅䆕ᅲ໻哴㚎ࡼ㛝ᑇ⒥㙠᳝ࡳ㛑ᗻ䩭ᬣᛳফԧ˄CaSR˅ⱘ㸼䖒DŽ ˄2˅ᧁ⼎㔎⇻ᯊ㚎ࡼ㛝ᑇ⒥㙠 CaSR 㸼䖒๲ࡴˈ䗮䖛֗䖯㸔ㅵᬊ㓽ǃ㸔ㅵ䞡ᵘখϢ㔎⇻ᗻ㚎ࡼ 㛝催य़˄PAH˅ⱘᔶ៤ˈҢᮄⱘ㾚㾝ᧁ⼎݊ߚᄤᴎࠊˈЎ㔎⇻ᗻ PAHⱘ䰆⊏ᦤկᮄᗱ䏃੠ᮄ䵊⚍DŽ થࠓࢅԅڑߏࢳ༰ูඕ ˄1˅㚎ࡼ㛝ᑇ⒥㙠᳝ࡳ㛑ᗻ䩭ᬣᛳফԧ˄CaSR˅ⱘ㸼䖒ˈ䖭ᰃ᥶䅼 CaSR ೼㚎ࡼ㛝催य़থ⫳Ё ⱘ԰⫼ҹঞৢ㓁ⷨおⱘࠡᦤ੠෎⸔DŽḍ᥂ K. WonnebergerㄝҎⱘ᭛⤂ ℆ˈ߸ᮁᶤ㒘㒛ᰃ৺ᄬ೼ CaSR 䳔⫼ߚᄤ⫳⠽ᄺᮍ⊩੠ࡳ㛑ᗻẔ偠䆕ᅲ˖(1)[Ca2+]o ๲ࡴৃᓩ䍋[Ca2+]i๲ࡴ˗(2) [Ca2+]i๲ࡴᴹ⑤Ѣ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 12 义 䩭ᑧࡼਬ˗(3) ໪䩭ݙ⌕䳔㒣䴲⬉य़ձ䌪ᗻ䩭䗮䘧˗(4) Gd3+ ੠ Ca 2+ ᰃ▔ࡼࠖ˗(5) CaSR䕀ᔩ੠㸼 䖒ⱘᄬ೼(⫼ PT-PCR ˈܡ⭿㒘࣪ nˈorthern blot, western blotㄝ䆕ᅲ)˄ K. Wonneberger, M.A. Scofield, P. Wangemann. Evidence for a calcium-sensing receptor in the vascular smooth muscle cells of the spiral modiolar artery.J Membr Biol. 2000 1;175 (3):203-12 DŽ˅៥Ӏ䗮䖛ⷨおݙᆍ˄1˅᠔⼎৘⾡Ⳍ݇ᅲ偠ˈᇚ ܙߚ䆕ᅲ㚎ࡼ㛝ᑇ⒥㙠㒚㚲᳝ CaSRⱘࡳ㛑ᗻ㸼䖒DŽ ˄2˅ϔ㠀䅸Ўˈ㚎㸔ㅵᬊ㓽ǃ䞡ᵘ੠ॳԡ㸔ᷧᔶ៤ᰃ㚎ࡼ㛝催य़˄PAH˅থ⫳থሩⱘ䞡㽕⮙⧚ ⫳⧚෎⸔DŽᴀᅲ偠ᢳ䗮䖛ᅲ偠䆕ᅲ㔎⇻˄ᇸ݊᜶ᗻ㔎⇻˅㛑Փ㚎ࡼ㛝ᑇ⒥㙠 CaSR㸼䖒๲໮ˈৢ㗙জ 䗮䖛㒚㚲ݙ䩭๲ࡴ֗䖯㚎㸔ㅵᬊ㓽ˈ䗮䖛䇗㡖㒚㚲ޟѵ੠㒚㚲๲Ⅺᓩ䍋㸔ㅵ䞡ᵘˈ䖯㗠ᇐ㟈㔎⇻ᗻ PAH ⱘথ⫳থሩDŽབᵰϞ䗄؛䆒ᕫࠄ䆕ᅲˈ䖭ᇚЎ㚎ࡼ㛝催य़ⱘĀCaSR ▔ࡼ؛䇈āᦤկ䗮䖛њമᅲ ⱘᅲ偠ձ᥂DŽⷨお៤ᵰᇚ݋᳝䞡㽕⧚䆎ᛣН੠┰೼ⱘᑨ⫼ࠡ᱃DŽ 3. થϰ௜ԅཙࡎֺ̣ރࢶ໻໿ד๥ ᴀ乍Ⳃⱘ⾥ⷨ䆒䅵ᇚձ᥂䱣ᴎˈᇍ✻੠䞡໡ⱘϝ໻ॳ߭DŽḍ᥂ϡৠᚙމˈߚ߿䞛⫼㒘䯈ᇍ✻੠ 㞾䑿ࠡৢᇍ✻ˈᑊ䖯㸠Ⳍᑨⱘ㒳䅵ߚᵤDŽ ď1Đಬིಁޙۤޏ೬াຬ 1˅ℷᐌ໻哴㚎ࡼ㛝ᑇ⒥㙠 CaSRⱘࡳ㛑ᗻ㸼䖒 èಬིՎ๞ġWister໻哴ˈԧ䞡 200-250g,䲠䲘ϡ᢬ˈ⏙⋕㑻ˈજए໻ࡼ⠽ЁᖗᦤկDŽ↣㒘 n=7-13(㾚݋ԧᚙމ㗠ᅮ)DŽ éᄷྑೋޔԅರဈૉէġ CaSR▔ࡼࠖ˖ GdCl3 0.3 mM ± 1 mM CaSRᡥࠊࠖ NPS2390 ��ȝ0 㙠⌚㔥˄SR˅䩭⋉ᡥࠊࠖ˖ Thapsigargin ��ȝ0 ⻋㛖䝊 C˄PLC˅ᡥࠊࠖ˖ U73122 ��ȝ0 U73122ⱘ㉏Ԑ⠽ U73343 ��ȝ0 䩴䩭Ѹᤶԧᡥࠊࠖ˖ NiCl2 10 mM L-ൟ䩭䗮䘧ᡥࠊࠖ˖ CdCl2 0.2 mM SR䩭ᑧ㗫チࠖ˖ Coffeine 10 mM ê࡮඘ಬֺི֥ġď܊ືĐ ëޏ೬াຬġ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 13 义 ೒ 1ℷᐌ໻哴㚎ࡼ㛝੠㚎ࡼ㛝ᑇ⒥㙠㒚㚲 CaSRⱘ㸼䖒ǃᅮԡǃࡳ㛑Ẕ⌟੠ᴎࠊ᥶䅼 2˅᜶ᗻ㔎⇻໻哴㚎ࡼ㛝ᑇ⒥㙠 CaSR㸼䖒ব࣪ঞ݊Ϣ㚎ࡼ㛝催य़ⱘ݇㋏ èಬིՎ๞ġৠϞ éᄷྑೋޔԅರဈૉէġৠϞ ê࡮඘ಬֺི֥ġď܊ືĐ ëޏ೬াຬġ A. CaSR৚৆ߖ๏ᇡᅢ࠮ޱౠ༯ྭݨቘᄜ ೒ 2 CaSR▔ࡼࠖ੠ᡥࠊࠖᇍᗹᗻ㔎⇻ᴵӊϟ㚎ࡼ㛝⦃㙠ᓴ࡯ⱘᕅડ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 14 义 B. ౧ᅢ๏ᇡܹཌྷ࠮ޱౠ CaSRؙܵና࠮ޱౠ࢝ᆥݨᄐࣴᅢ ೒ 3 ᜶ᗻ㔎⇻ᯊ໻哴㚎ࡼ㛝 CaSRⱘ㸼䖒Ϣ㚎ࡼ㛝催य़Ⳍ݇খ᭄ⱘব࣪ C. ๏ᇡ་࠮ޱౠ CaSRؙܵዼਉߖᆖࣸ᎚ࣕݨቘᄜ০ෆ৒ᎈ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 15 义 ೒ 4 㔎⇻ᇍ෍ݏ㚎ࡼ㛝ᑇ⒥㙠㒚㚲 CaSR㸼䖒੠㒚㚲๲Ⅺঞޟѵⱘᕅડঞֵ݊োӴᇐ䗮䏃 ď2Đཙࡎֺ֥ 1˅㚎ࡼ㛝㸔ㅵᓴ࡯ⱘ⌟ᅮ˖ ೑ᆊ㞾✊⾥ᄺ෎䞥⬇䇋к 2010⠜ ㄀ 16 义 Wister໻哴 2%៞Ꮘ↨ཹ䩴㝍㜨⊼ᇘ咏䝝˄ 2mg/kg DŽ˅ᓔ㛌পᖗ㛣੠㚎㛣 ゟˈे㕂Ѣ 4ćⲯ᳝ Hepes ⎆ⱘ෍ݏⲓЁˈԧ㾚ᰒᖂ㾷ࠪ䬰ϟˈ␌⾏Ⳉᕘ 0.3-0.7 mm㚎ݙ㚎ࡼ㛝ˈ䰸এ㸔ㅵ਼ೈ㛖㙾੠㒧㓨㒘 㒛ˈ࠾៤䭓ᑺ㑺Ў 3mm㸔ㅵ⦃ˈ ᣖ೼ϸḍ䩼ϱϝ㾦⦃Ϟ,ϔッᣖ೼ล᭭ᬃᶊϟ䴶ⱘ䪕䩽Ϟˈ㕂Ѣⲯ ᳝4ml Krebs⎆ᘦ⏽⍈ῑݙ,঺ϔッᣖ೼ᓴ࡯ᤶ㛑఼ⱘ⬉ᵕϞ ᣕˈ㓁䗮ҹ 95%O2-5%CO2⏋ড়⇨DŽ೼30 min ݙ䗤⏤㒭㚎ࡼ㛝⦃䋳㥋 0.3gⱘ෎⸔ᓴ࡯ˈᑇ㸵 1 hৢˈߚ߿⌟ᅮϡৠᴵӊϟⱘ㸔ㅵᓴ࡯DŽ Ǐখ㾕˖ Zhu D, Effros RM, Harder DR, Roman RJ, Jacobs ER (1998) Tissue sources of cytochrome P450 4A and 20-HETE xyntheses in rabbit lungs, Am J Respir Cell Mol Biol, 19,121-128 ǐ 2˅㚎ࡼ㛝ᑇ⒥㙠㒚㚲ⱘॳҷঞӴҷ෍ݏ˖ 䞛⫼Ċൟ㛊ॳ䝊⍜࣪⊩෍ݏ㚎ࡼ㛝ᑇ⒥㙠㒚㚲ⱘᮍ⊩[2]ˈेপ 200gᎺেⱘ໻哴ˈ⫼ 2ml∈ড়∃ 䝯咏䝝DŽ ᇚ咏䝝ৢⱘ໻哴೎ᅮѢ᠟ᴃৄˈ⫼䜦㊒ẝᇍ໻哴㸼䴶Ⲃ㙸䖯㸠⍜↦DŽ⊓ⴔ໻哴ࠥさ䚼ԡ࠾ ᓔ㛌㜨ˈᲈ䴆ᖗ㛣੠㚎䚼ˈ⫼䬞ᄤ䕏ᦤᖗ㛣ˈ⊓⇨ㅵ໘পϟ㚎䚼ˈ㟇Ѣ PBS 㓧ކ⎆ЁDŽᇚ㚎৊೎ᅮ Ѣ⸙㛊ᵓϞˈ⫼ᰒᖂ᠟ᴃ࠾೼ԧᓣᰒᖂ䬰ϟপߎ䖰ッ㚎ࡼ㛝ˈএݙⲂৢ⫼࠾ߔᇚ㸔ㅵ࠾៤⹢ഫˈ㕂 ѢĊൟ㛊ॳ䝊Ё⍜࣪៤㍂⢊DŽ ⫼ 20% DMEM催㊪෍ݏ⎆㒜ℶ⍜࣪ৢˈ⫼ 2000䕀⾏ᖗ 5ߚ䩳ˈপϟሖ ≝⎔ˈ⫼෍ݏ⎆䞡 ˈᬒѢ෍ݏ⫊Ё෍ݏDŽ䱨໽䖯㸠ᤶ⎆ˈϔ਼ৢ䖯㸠䡈ᅮDŽ ॳҷ෍ݏ㒚㚲䭓⒵⫊ᑩ80%-90% े ৃӴҷ෍ݏˈপ㄀2-4ҷ⫳䭓㡃དⱘ⫼Ѣᅲ偠DŽӴҷ෍ݏⱘ㚎 ࡼ㛝ᑇ⒥㙠㒚㚲䭓㟇60%Ꮊে㵡ড়ᯊˈᤶ᮴㸔⏙෍ݏ24hˈ䖯㸠ᅲ偠DŽ Ǐখ㾕˖