Title Serotonergic Circuit for Respiratory Modulation under HypoxicExposure( 内容と審査の要旨(Summary) ) Author(s) 森永, 涼介 Report No.(Doctoral Degree) 博士(獣医学) 甲第520号 Issue Date 2019-03-13 Type 博士論文 Version none URL http://hdl.handle.net/20.500.12099/77951 ※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。
Ặྡ㸦ᮏ㸦ᅜ㸧⡠㸧 ᳃ Ọ ᾴ 㸦బ㈡┴㸧 ᣦ ᑟ ᩍ ဨ Ặ ྡ ᒱ㜧Ꮫ ᩍᤵ ᒣ ᮏ Ḡ 㑻 Ꮫ ࡢ ✀ 㢮 ༤ኈ㸦⋇་Ꮫ㸧 Ꮫ グ ␒ ྕ ⋇་༤⏥➨㸳㸰㸮ྕ Ꮫ ᤵ ᖺ ᭶ ᪥ ᖹᡂ㸱㸯ᖺ㸱᭶㸯㸱᪥ Ꮫ ᤵ ࡢ せ ௳ Ꮫつ๎➨㸲᮲➨㸯㡯ヱᙜ ◊ ✲ ⛉ ཬ ࡧ ᑓ ᨷ 㐃ྜ⋇་Ꮫ◊✲⛉ ⋇་Ꮫᑓᨷ ◊✲ᣦᑟࢆཷࡅࡓᏛ ᒾᡭᏛ Ꮫ ㄽ ᩥ 㢟 ┠ 6HURWRQHUJLF&LUFXLWIRU5HVSLUDWRU\0RGXODWLRQ XQGHU+\SR[LF([SRVXUH 㸦ప㓟⣲ᭀ㟢ࡢ྾ㄪ⠇࠾ࡅࡿࢭࣟࢺࢽࣥసື ᛶ⚄⤒ᅇ㊰㸧 ᑂ ᰝ ጤ ဨ ᰝ ᒾ ᡭ Ꮫ ᩍ ᤵ Ᏹ ሯ 㞝 ḟ ᰝ ᖏᗈ␆⏘Ꮫ ᩍ ᤵ ᮧ ᘏ ኵ ᰝ ᒾ ᡭ Ꮫ ᩍ ᤵ ᒣ ᮏ Ḡ 㑻 ᰝ ᮾி㎰ᕤᏛ ᩍ ᤵ ᰘ ⏣ ⚽ ྐ ᰝ ᒱ 㜧 Ꮫ ᩍ ᤵ 㜿 㛢 Ὀ 㑻 Ꮫㄽᩥࡢෆᐜࡢせ᪨ ᘏ㧊⭡ഃ྾⩌㸦VRC㸧ࡣᘏ㧊⭡እഃ㸦VLM㸧Ꮡᅾࡋ㸪Bötzinger complex㸦BC㸧㸪
pre-Bötzinger complex㸦PBC㸧㸪 rostral ventral respiratory group㸦rVRG㸧㸪caudal ventral respiratory group㸦cVRG㸧ࡢ㡿ᇦศࡅࡽࢀ㸪┦㐃⤡ࡍࡿࡇ࡛㸪྾ࣃࢱ࣮
ࣥࢆᙧᡂࡋ࡚࠸ࡿࠋᮏ◊✲࡛ࡣ㸪ప㓟⣲ᭀ㟢ᑐࡍࡿ྾ᛂ⟅ࢭࣟࢺࢽࣥ㸦5-HT㸧సື ᛶ⚄⤒ࡀ㛵ࡍࡿࡇὀ┠ࡋ㸪⦭⥺᰾ 5-HT సືᛶ⚄⤒ࡢ VRC ࡢᢞᑕࢆ⚄⤒ᶆ㆑ἲ ࡼࡾ᫂ࡽࡍࡿࡶᏙ᮰᰾㸦NTS㸧ࡸ VRC ࢆྵࡵࡓᘏ㧊య࡛ࡢప㓟⣲ᭀ㟢 ࡼࡿ5-HT 㝧ᛶᛂࡢኚࢆච⤌⧊Ꮫⓗゎᯒࡋࡓࠋ ⦭⥺᰾ࡽ VRC యࡢ 5-HT సືᛶ⚄⤒ࡢᢞᑕࢆ᫂ࡽࡍࡿࡇࢆ┠ⓗࡋ㸪 Wistar ࣛࢵࢺ㸦㞝㸪8-9 㐌㱋㸧ࡢ BC㸪PBC㸪rVRG ๓㒊㸪rVRG ᚋ㒊/cVRG ࡢ 4 㡿ᇦ㸪 ㏫⾜ᛶ⚄⤒ᶆ㆑≀㉁࡛࠶ࡿࢥࣞࣛࢺ࢟ࢩࣥ B ࢧࣈࣘࢽࢵࢺ㸦CTB㸧ࢆࡑࢀࡒࢀὀධࡋ㸪1 㐌㛫ᚋ4㸣ࣃ࣒ࣛ࣍ࣝࣝࢹࣄࢻ㸦PFA㸧࡛℺ὶᅛᐃࡋ㸪CTB ࠾ࡼࡧ 5-HT ྜᡂࡢᚊ㏿ 㓝⣲࡛࠶ࡾ5-HT సືᛶ⚄⤒ࢆᶆ㆑ࡍࡿࢺࣜࣉࢺࣇࣥỈ㓟㓝⣲ 2㸦TPH2㸧ᑐࡍࡿᢠ యࢆ⏝࠸ࡓච⤌⧊Ꮫࡼࡾ㸪⦭⥺᰾࠾ࡅࡿCTB ࠾ࡼࡧ TPH2 㝧ᛶᛂࢆ♧ࡍ⚄⤒ ࢆ᳨⣴ࡋࡓࠋࡢὀධ࠾࠸࡚ࡶ㸪CTB 㝧ᛶࢆ♧ࡍ⚄⤒⣽⬊యࡣ࿀ഃ⦭⥺᰾⩌࠾ࡼࡧᑿ ഃ⦭⥺᰾⩌ᗈࡃㄆࡵ࡚࠸ࡿࠋCTB 㝧ᛶ⚄⤒ࡢ⣽⬊యࡣᙧ㸪ᴃᙧࡲࡓࡣከゅᙧ࡛࠶ࡾ㸪 」ᩘࡢᶞ≧✺㉳ࢆ᭷ࡋ㸪ࢧࢬࡣ 67-976 μm2࡛࠶ࡿࡇࢆ♧ࡋࡓࠋࡲࡓ㸪⦭⥺᰾ㄆࡵ ࡽࢀࡓCTB 㝧ᛶ⚄⤒ࡢ୍㒊ࡣ TPH2 㝧ᛶᛂࢆ♧ࡋ㸪CTB/TPH2 ඹ㝧ᛶ⚄⤒ࡢ⣽⬊య ࡣᆺࡢࡶࡢࡀㄆࡵࡽࢀ࡞࠸ࡇࢆ♧ࡋࡓࠋ㒊ศࡢὀධ࠾࠸࡚ CTB/TPH2 ඹ㝧ᛶ ⚄⤒ࡣ㸪࿀ഃ⦭⥺᰾⩌࡛࠶ࡿ⫼ഃ⦭⥺᰾࠾ࡼࡧᑿഃ⦭⥺᰾࡛࠶ࡿ⦭⥺᰾㸪ᕧ⣽⬊⥙ᵝ᰾㸪 ഐᕧ⣽⬊⥙ᵝ᰾㸪☜⦭⥺᰾㸪ῐ⦭⥺᰾ከࡃㄆࡵࡽࢀ㸪ࡑࡢࡢ⦭⥺᰾ࡣᑡᩘ࡛࠶ 㸦㸱㸧
ࡗࡓࠋ௨ୖࡢ⤖ᯝࡽ㸪࿀ഃ⦭⥺᰾⩌ࡽᑿഃ⦭⥺᰾⩌ࡢᗈ࠸⠊ᅖศᕸࡍࡿ 5-HT సື ᛶ⚄⤒ࡀ㸪VRC యᢞᑕࡋ࡚࠸ࡿࡇࢆ᫂ࡽࡋࡓࠋ ḟ㸪NTS ࡸ VRC ࢆྵࡴᘏ㧊య࠾ࡅࡿప㓟⣲ᭀ㟢ࡼࡿ 5-HT 㝧ᛶᛂࡢኚࢆ ᫂ࡽࡍࡿࡇࢆ┠ⓗࡋ࡚㸪Wistar ࣛࢵࢺࢆప㓟⣲࢞ࢫ㸦10㸣O2㸧1㸪2㸪4㸪6 㛫ᭀ㟢ࡋࡓᚋ㸪4㸣PFA ࡛℺ὶᅛᐃࡋ㸪5-HT ᑐࡍࡿᢠయࢆ⏝࠸࡚ච⤌⧊Ꮫⓗ᳨ウࢆ ⾜ࡗࡓࠋࡲࡓ㸪5-HT సືᛶ⚄⤒ࡢ⚄⤒ࡢ㛵ಀࢆ᫂ࡽࡍࡿࡓࡵ㸪5-HT ຍ࠼㸪 PBC ࡢ⚄⤒Ⓨ⌧ࡍࡿࢽ࣮ࣗࣟ࢟ࢽࣥ 1 ཷᐜయ㸦NK1R㸧ࡸ A1/C1 ࠾ࡼࡧ A2/C2 ࢝ࢸࢥ ࣑ࣛࣥసືᛶ⚄⤒ࢆᶆ㆑ࡍࡿࢻࣃ࣑ࣥβ Ỉ㓟㓝⣲㸦DBH㸧ᑐࡍࡿᢠయࢆ⏝࠸࡚ከ㔜⺯ ගචᰁⰍࢆ⾜ࡗࡓࠋప㓟⣲ᭀ㟢2 㛫⩌࠾࠸࡚㸪࿀ഃ⦭⥺᰾⩌࠾ࡼࡧᑿഃ⦭⥺᰾⩌ య࡛ 5-HT 㝧ᛶᛂࢆ♧ࡍ⚄⤒⣽⬊యᩘࡀ㠀ప㓟⣲ᭀ㟢⩌ࡼࡾቑຍࡋࡓࠋ5-HT 㝧ᛶ⚄⤒ ⥺⥔ࡣᘏ㧊ࡢᗈ࠸⠊ᅖศᕸࡋ㸪ప㓟⣲ᭀ㟢2 㛫⩌ࡢ 5-HT 㝧ᛶ⚄⤒⥺⥔ࡣ㠀ప㓟⣲ᭀ 㟢⩌ẚ㍑ࡋ㸪ከࡃㄆࡵࡓࠋࡑࢀࡒࢀࡢ⚄⤒᰾࠾࠸࡚ 5-HT 㝧ᛶ⚄⤒⥺⥔ࡢᢞᙳ㠃✚ࢆ 㠀ప㓟⣲ᭀ㟢⩌ẚ㍑ࡋࡓࡇࢁ㸪ࡍ࡚ࡢప㓟⣲ᭀ㟢⩌ࡢ࿀ഃ VLM ࠾ࡼࡧప㓟⣲ᭀ㟢 2㸪4㸪6 㛫⩌ࡢᑿഃ VLM ࠾࠸࡚㸪᭷ពቑຍࡋࡓࠋࡲࡓ㸪᰾㸦Amb㸧⦓ᐦ㒊࠾ ࠸࡚ࡶ㸪ࡍ࡚ࡢప㓟⣲ᭀ㟢⩌࡛ቑຍഴྥࡀ࠶ࡿࡇ㸪ప㓟⣲ᭀ㟢1㸪2 㛫⩌ࡢ NTS እ ഃ㒊ࡸDMX ࠾࠸࡚ࡶ᭷ព࡞ቑຍࡀ࠶ࡿࡇࢆ♧ࡋࡓࠋከ㔜⺯ගචᰁⰍ࠾࠸࡚ࡣ㸪 ㍈⣴⒗ࢆ᭷ࡍࡿ5-HT 㝧ᛶ⚄⤒⥺⥔ࡀ㸪 NK1R 㝧ᛶ⚄⤒ࡸ DBH 㝧ᛶ⚄⤒ࡢᶞ≧✺㉳ࡸ⣽ ⬊యࡑࢀࡒࢀ᥋ࡋ࡚࠸ࡿᵝᏊࢆ᫂ࡽࡋࡓࠋ௨ୖࡢ⤖ᯝࡽ㸪ప㓟⣲ᭀ㟢ୗ࡛ࡣ㸪⦭ ⥺᰾ᇦࡢ5-HT సືᛶ⚄⤒࡛ 5-HT ྜᡂࢆஹ㐍ࡋ㸪ᘏ㧊ࡢᗈ࠸⠊ᅖ࡛ 5-HT ศἪࢆஹ㐍 ࡍࡿࡇࢆ♧၀ࡋࡓࠋࡲࡓ㸪5-HT సືᛶ⚄⤒ࡣ VRC ࡛࠶ࡿ PBC ࡢ⚄⤒ࢆࡋ࡚┤᥋ⓗ ྾ࢆㄪ⠇ࡋ࡚࠸ࡿࡔࡅ࡛࡞ࡃ㸪A1/C1 ⚄⤒࡞ࡢ྾㛵ಀࡍࡿ⚄⤒ࢆࡋ࡚㛫᥋ⓗ ྾ࢆㄪ⠇ࡍࡿྍ⬟ᛶࢆ♧ࡋࡓࠋ ᮏ◊✲ࡢ⤖ᯝࡣ㸪ప㓟⣲ᭀ㟢ࡢ㝿㸪࿀ഃ⦭⥺᰾⩌ᑿഃ⦭⥺᰾⩌ࡢ୧᪉ࡢ 5-HT సື ᛶ⚄⤒ࡀప㓟⣲ᭀ㟢ࡼࡾ5-HT ྜᡂࢆஹ㐍ࡋ㸪VRC ࡛ࡢ 5-HT ศἪࢆஹ㐍ࡍࡿࡇࢆ♧ ࡋ࡚࠸ࡿࠋࡇࢀࡽࡢ5-HT ࡣ㸪VRC ࡢάືࢆㄪ⠇ࡋ࡚ప㓟⣲ᑐࡍࡿ྾ᛂ⟅ࢆ⏕ࡌࡉࡏ ࡿ⪃࠼ࡽࢀࡓࠋࡉࡽ㸪5-HT సືᛶ⚄⤒ࡣ㸪NTS ࡸឤ⚄⤒άືࢆㄪ⠇ࡍࡿ A1/C1 ⚄ ⤒㸪A2/C2 ⚄⤒㸪ឤ⚄⤒άືࢆㄪ⠇ࡍࡿ Amb ࡸ DMX ࡢ⚄⤒ࡢάືࢆㄪ⠇ࡍࡿࡇ ࡛㸪㛫᥋ⓗ྾ࢆㄪ⠇ࡋ࡚࠸ࡿྍ⬟ᛶࡀ࠶ࡿࠋ௨ୖࡢ⤖ᯝࡣ㸪ప㓟⣲ᭀ㟢ࡢ྾ㄪ⠇ ࠾ࡅࡿ5-HT ࡢ㔜せᛶࢆ♧ࡋࡓࡶࡢ࡛࠶ࡿࠋ ᑂ ᰝ ⤖ ᯝ ࡢ せ ᪨ ᘏ㧊⭡ഃ྾⩌㸦VRC㸧ࡣ pre-Bötzinger complex㸦PBC㸧ࢆ୰ᚰ྾ࣃࢱ࣮ࣥࢆᙧ ᡂࡋ࡚࠾ࡾ㸪ప㓟⣲ᭀ㟢ୗ࡛ࡣ㸪⾑୰㓟⣲⃰ᗘࡢపୗࢆཷᐜࡋࡓᮎᲈᏛཷᐜჾࡢ⯆ዧࡀ Ꮩ᮰᰾ࢆࡋ࡚ VRC ఏ࠼ࡽࢀࡿࡇ࡛㸪Ẽ㔞ࡢቑຍࡀ⏕ࡌࡿࡇࡀ▱ࡽࢀ࡚࠸ࡿࠋ ࡇࡢప㓟⣲ᭀ㟢ᑐࡍࡿ྾ᛂ⟅㸪ࢭࣟࢺࢽࣥ㸦5-HT㸧సືᛶ⚄⤒ࡀ㛵ࡋ࡚࠸ࡿࠋ5-HT సືᛶ⚄⤒ࡢ⣽⬊యࡣ⦭⥺᰾⩌ศᕸࡋ࡚࠾ࡾ㸪5-HT సືᛶ⚄⤒⥺⥔ࡣ VRC ࢆྵࡵࡓ ྾㛵ಀࡍࡿ⚄⤒ࡀศᕸࡍࡿ㡿ᇦᗈࡃᏑᅾࡍࡿࠋࡋࡋ㸪VRC ࡢ 5-HT సືᛶ⚄⤒ࡢ ᢞᑕᵝᘧࡸప㓟⣲ᭀ㟢ୗ࡛ 5-HT సືᛶ⚄⤒ࡀㄪ⠇ࢆ⾜࠺⚄⤒᰾ࡢヲ⣽ࡣ᫂ࡽ࡛࡞࠸ࠋ ࡑࡇ࡛㸪ᮏ◊✲࡛ࡣప㓟⣲ᭀ㟢ୗࡢ྾ㄪ⠇࠾ࡅࡿ 5-HT సືᛶ⚄⤒ᅇ㊰ࢆ᫂ࡽࡍ ࡿࡓࡵ㸪⚄⤒ᶆ㆑ἲ࠾ࡼࡧච⤌⧊Ꮫἲࡼࡿゎᯒࢆ⾜ࡗࡓࠋ ࡲࡎ㸪㏫⾜ᛶ⚄⤒ᶆ㆑≀㉁ࢆ⏝࠸ࡓゎᯒࡼࡗ࡚㸪࿀ഃ⦭⥺᰾⩌࠾ࡼࡧᑿഃ⦭⥺᰾⩌ࡢ ᗈ࠸⠊ᅖศᕸࡍࡿ 5-HT సືᛶ⚄⤒ࡀ VRC యᢞᑕࡋ࡚࠸ࡿࡇࢆ᫂ࡽࡋࡓࠋ ࡇࡢ⤖ᯝࡽ㸪⦭⥺᰾యศᕸࡍࡿ 5-HT సືᛶ⚄⤒ࡀ VRC ࡢ⚄⤒άືࢆㄪ⠇ࡋ㸪┤ ᥋ⓗ྾ࢆኚࡉࡏࡿ⏦ㄳ⪅ࡣ⪃ᐹࡋࡓࠋ5-HT ᑐࡍࡿᢠయࢆ⏝࠸ࡓච⤌⧊Ꮫ
࡛ࡣ㸪ప㓟⣲࢞ࢫ㸦10㸣O2㸧ᭀ㟢ࡋࡓࣛࢵࢺࡢ⦭⥺᰾⩌యࡢ5-HT 㝧ᛶ⚄⤒⣽⬊యࡸ ᘏ㧊యㄆࡵࡽࢀࡿ 5-HT 㝧ᛶ⚄⤒⥺⥔ࡀ㸪ᭀ㟢ࢆ⾜ࡗ࡚࠸࡞࠸ࣛࢵࢺẚ㸪ከࡃㄆ ࡵࡽࢀࡿࡇࢆ᫂ࡽࡋࡓࠋࡲࡓ㸪㍈⣴⒗ࢆ᭷ࡍࡿ5-HT 㝧ᛶ⚄⤒⥺⥔ࡣ㸪PBC ࡢ⚄⤒ ࡸᘏ㧊ࡢ࢝ࢸࢥ࣑ࣛࣥసືᛶ⚄⤒ࡢᶞ≧✺㉳ࡸ⣽⬊యࡑࢀࡒࢀ᥋ࡋ࡚࠸ࡿࡇࢆ᫂ࡽ ࡋࡓࠋࡇࢀࡽࡢ⤖ᯝࡽ㸪ప㓟⣲ᭀ㟢ࡼࡾ⦭⥺᰾యศᕸࡍࡿ 5-HT సືᛶ⚄⤒ࡢ 5-HT ྜᡂࡀஹ㐍ࡋ㸪ᘏ㧊య࡛ 5-HT ࢆศἪࡋ࡚࠸ࡿ⏦ㄳ⪅ࡣ⪃ᐹࡋࡓࠋࡲࡓ㸪5-HT సືᛶ⚄⤒ࡣ VRC ࡢ⚄⤒άືࢆ┤᥋ㄪ⠇ࡋ࡚࠸ࡿࡔࡅ࡛࡞ࡃ㸪࢝ࢸࢥ࣑ࣛࣥసືᛶ⚄⤒ ࡞ࡢVRC ௨እࡢ⚄⤒ࢆࡋ࡚㸪㛫᥋ⓗ྾ࢆㄪ⠇ࡋ࡚࠸ࡿ⏦ㄳ⪅ࡣ⪃ᐹࡋࡓࠋ ௨ୖࡢᵝ㸪ᮏㄽᩥ࡛ࡣ⚄⤒ᶆ㆑ἲ࠾ࡼࡧච⤌⧊Ꮫἲࡼࡗ࡚㸪ప㓟⣲ᭀ㟢ୗ࠾ ࡅࡿ VRC యࡢ⚄⤒άືࡢㄪ⠇⦭⥺᰾యࡢ 5-HT సືᛶ⚄⤒ࡀ㛵ࡋ࡚࠸ࡿࡇࢆ ᫂ࡽࡋࡓࠋࡲࡓ㸪5-HT సືᛶ⚄⤒ࡣ㸪VRC ࡔࡅ࡛࡞ࡃ㸪VRC ௨እࡢ⚄⤒ࡢάືࢆㄪ ⠇ࡍࡿࡇ࡛㛫᥋ⓗ྾ࢆㄪ⠇ࡋ࡚࠸ࡿྍ⬟ᛶࡀ࠶ࡿࡇࡶ♧ࡋࡓࠋᮏ◊✲ࡀ᪂ࡋࡃᥦ ♧ࡋࡓప㓟⣲ᭀ㟢ୗࡢ྾ᛂ⟅࠾ࡅࡿ 5-HT సືᛶ⚄⤒ࡢㄪ⠇ᅇ㊰ࡣ㸪」㞧࡞୰ᯡᛶ ྾ㄪ⠇ᅇ㊰ࡢゎ᫂ࡍࡿୖ࡛㔜せ࡞ᇶ♏ᡤぢ࡞ࡾᚓࡿࡶࡢ࡛࠶ࡿࠋ ௨ୖࡘ࠸࡚㸪ᑂᰝጤဨဨ୍⮴࡛ᮏㄽᩥࡀᒱ㜧ᏛᏛ㝔㐃ྜ⋇་Ꮫ◊✲⛉ࡢᏛㄽ ᩥࡋ࡚༑ศ౯್ࡀ࠶ࡿㄆࡵࡓࠋ ᇶ♏࡞ࡿᏛ⾡ㄽᩥ
㸯㸧㢟 ┠㸸 Hypoxia-induced increases in serotonin-immunoreactive nerve fibers in the medulla oblongata of the rat
ⴭ ⪅ ྡ㸸 Morinaga, R., Nakamuta, N. and Yamamoto, Y. Ꮫ⾡㞧ㄅྡ㸸 Acta Histochemica
ᕳ࣭ྕ࣭㡫࣭Ⓨ⾜ᖺ㸸118㸦8㸧㸸806817㸪2016
㸰㸧㢟 ┠㸸 Serotonergic projections to the ventral respiratory column from raphe nuclei in rats
ⴭ ⪅ ྡ㸸 Morinaga, R., Nakamuta, N. and Yamamoto, Y. Ꮫ⾡㞧ㄅྡ㸸 Neuroscience Research
ᕳ࣭ྕ࣭㡫࣭Ⓨ⾜ᖺ㸸In Press ᪤Ⓨ⾲Ꮫ⾡ㄽᩥ
㸯㸧㢟 ┠㸸 Differences in respiratory changes and Fos expression in the
ventrolateral medulla of rats exposed to hypoxia, hypercapnia, and hypercapnic hypoxia
ⴭ ⪅ ྡ㸸 Wakai, J., Takamura, D., Morinaga, R., Nakamuta, N. and Yamamoto, Y.
Ꮫ⾡㞧ㄅྡ㸸 Respiratory Physiology & Neurobiology
ᕳ࣭ྕ࣭㡫࣭Ⓨ⾜ᖺ㸸215㸸64-72㸪2015
㸰㸧㢟 ┠㸸 Time-dependent changes in cardiorespiratory functions of anesthetized rats exposed to sustained hypoxia
ⴭ ⪅ ྡ㸸 Kato, K., Morinaga, R., Fushuku, S., Nakamuta, N. and Yamamoto, Y.
Ꮫ⾡㞧ㄅྡ㸸 Autonomic Neuroscience : Basic and Clinical ᕳ࣭ྕ࣭㡫࣭Ⓨ⾜ᖺ㸸212㸸19㸪2018
