Suppression of aortic expansion and contractile recovery in a rat abdominal aortic aneurysm model by biodegradable gelatin hydrogel sheet incorporating basic fibroblast growth factor

Title

Suppression of aortic expansion and contractile recovery in a rat

abdominal aortic aneurysm model by biodegradable gelatin

hydrogel sheet incorporating basic fibroblast growth factor( 要約

版(Digest) )

Author(s)

河合, 憲一

Report No.(Doctoral

Degree)

博士(医学) 甲第1076号

Issue Date

2018-03-25

Type

博士論文

Version

none

URL

http://hdl.handle.net/20.500.12099/75215

※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。

࣏ࣜࢪࢺࣜ㛵ಀ㸦ู⣬㸲㸧

Repository㸦Form4㸧





Ꮫ఩ㄽᩥせ⣙

Extended Summary in Lieu of the Full Text of a Doctoral Thesis

Ặ ྡ㸸

Full Name

Ἑྜ ᠇୍

Ꮫ఩ㄽᩥ㢟┠㸸

Thesis Title

Suppression of aortic expansion and contractile recovery in a rat abdominal aortic aneurysm model by biodegradable gelatin hydrogel sheet incorporating basic fibroblast growth factor

Ꮫ఩ㄽᩥせ⣙㸸

Summary of Thesis ࠙⫼ᬒ࡜┠ⓗࠚ ⭡㒊኱ື⬦⒗ࡢ἞⒪ࡣື⬦⒗⮬యࢆእ⛉ⓗ࡟⨨᥮ࡍࡿேᕤ⾑⟶⨨᥮⾡ࡀ୺ὶ࡛࠶ࡗࡓࡀ㸪㏆ᖺ㸪⾑⟶ෆ἞⒪ ࡜ࡋ࡚ࢫࢸࣥࢺࢢࣛࣇࢺෆᤄ⾡ࡀ⾜ࢃࢀࡿ㢖ᗘࡀቑ኱ࡋ࡚࠸ࡿࠋࢫࢸࣥࢺࢢࣛࣇࢺෆᤄ⾡ࡣ㛤⭡࡟ࡼࡿேᕤ ⾑⟶⨨᥮⾡࡟ẚ࡭࡚ࡼࡾప౵く࡛࠶ࡾ㸪᭱㏆࡛ࡣᒁᡤ㯞㓉ୗ࡛ࡢ἞⒪ࡶቑຍࡋ࡚࠸ࡿࠋࡋ࠿ࡋேᕤ⾑⟶⨨᥮ ⾡࡛ࡣ⑓ኚ㒊఩ࢆษ㝖ࡍࡿࡀࢫࢸࣥࢺࢢࣛࣇࢺෆᤄ⾡࡛ࡣ⮬ᕫࡢ⾑⟶㸦ື⬦⒗ቨ㸧ࡣࡑࡢࡲࡲṧᏑࡍࡿࡓࡵ㸪 ἞⒪ᑐ㇟㒊఩⾑⟶࡟࠾ࡅࡿࢫࢸࣥࢺࢢࣛࣇࢺෆᤄᚋࡢ୰ᯡഃ኱ື⬦࡛ࡢࢢࣛࣇࢺ QHFN ࡢ PLJUDWLRQ ࡸ W\SH ,, ࡟ศ㢮ࡉࢀࡿHQGROHDN ࡟ࡼࡿື⬦⒗ࡢ෌ᣑ኱ࡀ㐲㝸ᮇࡢ◚⿣ࡸṚஸࡢཎᅉ࡜࡞ࡗ࡚࠾ࡾ㸪἞⒪ୖࡢၥ㢟 Ⅼ࡛࠶ࡿ࡜⪃࠼ࡿࠋື⬦⒗ࡢᣑ኱ࢆ⸆๣ᢞ୚࡟ࡼࡾᢚไࡍࡿ◊✲ࡣከࡃ⾜ࢃࢀ࡚࠾ࡾ㸪ࡑࡢ୰࡛ EDVLF ILEUREODVWJURZWKIDFWRU㸦௨ୗ E)*)㸧ࡣ⥺⥔ⱆ⣽⬊ቑṪస⏝㸪⾑⟶᪂⏕స⏝ࢆᣢࡕ㸪෌⏕἞⒪࡟࠾࠸࡚ ᵝࠎ࡞ᐇ㦂ሗ࿌ࡀࡉࢀ࡚࠸ࡿࠋ  ᮏ◊✲࡛ࡣ㸪⸆๣ᢞ୚࡟ࡼࡿື⬦⒗ࡢᶵ⬟ⓗᨵၿࢆホ౯ࡍࡿࡓࡵ࡟㸪E)*) ࢆྵᾐࡉࡏࡓ⏕≀ศゎᛶࣁ࢖ࢻ ࣟࢤࣝࢩ࣮ࢺ㸦ELRGHJUDGDEOHJHODWLQK\GURJHOVKHHW ௨ୗ %*+6㸧ࢆ⏝࠸࡚ࣛࢵࢺື⬦⒗ࣔࢹࣝ࡟࠾࠸࡚⒗ ࡢᣑ኱ᢚไ࡜ື⬦ቨࡢ⾑⟶཰⦰ຊࡢᨵၿࡀᚓࡽࢀ࠿ྰ࠿ࢆ᳨ウࡋࡓࠋ ࠙ᑐ㇟࡜᪉ἲࠚ 6SUDJXH'DZOH\ ⣔㞝ᛶࣛࢵࢺ㸦 㐌㱋㸪J㸧ࢆ౑⏝ࡋ㸪௨ୗࡢ㸲⩌ࢆసᡂࡋࡓࠋ&RQWURO ⩌㸸୍᫬ ⤖⣻ࡋࡓ⭡㒊኱ື⬦ෆ࡟⏕⌮㣗ሷỈࢆ PP+J ࡛  ศ㑏ὶࡋࡓ⩌㸪(ODVWDVHRQO\ ⩌㸸ྠᵝࡢᡭ㡰࡛㇜⮅⮚ ⏤᮶ (ODVWDVH ༢఩ࢆ℺ὶࡋࡓ⩌㸪+\GURJHO ⩌㸸(ODVWDVH ࢆ℺ὶࡋࡓື⬦࡟⏕⌮㣗ሷỈࢆྵᾐࡉࡏࡓ %*+6 ࢆ⿕そࡋࡓ⩌㸪E)*) ⩌㸸(ODVWDVH ࢆ℺ὶࡋࡓື⬦࡟ E)*)ȣJ ࢆྵᾐࡉࡏࡓ %*+6 ࢆ⿕そࡋࡓ⩌ࠋྛ⩌  ౛ࡎࡘ࡟ᑐࡋ௨ୗࡢ஦㡯࡟ࡘࡁ⤫ィᏛⓗᡭἲࢆ⏝࠸࡚ẚ㍑᳨ウࡋ㸪S ࢆ᭷ពᕪ࠶ࡾ࡜ࡋࡓࠋձ⾡๓㸪 ⾡ᚋ  ᪥㸪⾡ᚋ  ᪥ࡢ㉸㡢Ἴィ ࡟ࡼࡿ⭡㒊኱ື⬦⒗᭱኱ᚄࡢᖹᆒ㸪ղ⾡ᚋ  ᪥ࡢື⬦ᚄࡢ⾡๓࡟ẚ㍑ࡋ ࡓᣑ኱⋡㸪ճ⾡ᚋ  ᪥㸦௨ୗྠᵝ㸧ࡢື⬦⒗⾑⟶࡟࠾ࡅࡿᙎᛶ⧄⥔ࡢ๭ྜ㸪մȘᖹ⁥➽࢔ࢡࢳࣥ㸦Ș60$㸧 㝧ᛶ⣽⬊ࡢ๭ྜ㸪յື⬦⒗⾑⟶ࣜࣥࢢࡢ཰⦰సື⸆ᢞ୚᫬ࡢᖹᆒ཰⦰ຊࡢ⤒᫬ⓗ᥎⛣㸪ն཰⦰సື⸆ᢞ୚᫬ ࡢ᭱኱཰⦰ຊ ࠙⤖ᯝࠚ

ձ ⾡ᚋ  ᪥࡟࠾࠸࡚ &RQWURO ⩌࡟ẚ࡭ (ODVWDVHRQO\ ⩌㸪+\GURJHO ⩌㸪E)*) ⩌࡜ࡶ࡟᭷ព࡟⾑⟶ᚄࡣᣑ ኱ࡋࡓࠋࡲࡓ E)*) ⩌ࡣ㸪(ODVWDVHRQO\ ⩌࡟ẚ࡭࡚᭷ព࡟⾑⟶ᚄࡣ⦰ᑠࡋࡓࠋ

ղ &RQWURO ⩌ࡢື⬦ᚄᣑ኱⋡ࡣ  ᪥┠࡛⾡๓ࡢ  ಸ㏆ࡃࡢ s࡛࠶ࡗࡓࠋ(ODVWDVHRQO\ ⩌࡜ +\GURJHO ⩌ࡢᣑ኱⋡ࡣ㸪ࡑࢀࡒࢀ s㸪s࡛࠶ࡾ㸪&RQWURO ⩌࡟ẚ࡭࡚᭷ព࡟ቑຍࡋࡓࠋE)*) ⩌ࡢᣑ ኱⋡ࡣ s࡛࠶ࡾ㸪&RQWURO ⩌࡟ẚ࡭࡚᭷ព࡞ቑຍࡣㄆࡵ࡞࠿ࡗࡓࡀ㸪(ODVWDVHRQO\ ⩌࡜ẚ㍑ࡋ ᭷ព࡟ᢚไࡉࢀࡓࠋ

ճ ᙎᛶ⧄⥔ࡢ๭ྜࡣ &RQWURO ⩌࡛ s࡜᭱ࡶከࡃ㸪ࡇࢀ࡟ẚ㍑ࡋ (ODVWDVHRQO\ ⩌ࡣ s࡛ ࠶ࡾ㸪᭷ព࡟ప࠸๭ྜ࡛࠶ࡗࡓࠋ+\GURJHO ⩌ࡣ s࡛࠶ࡾ &RQWURO ⩌࡟ẚ࡭᭷ព࡟ప࠿ࡗࡓࡀ㸪

(ODVWDVHRQO\ ⩌࡟ẚ࡭ࡿ࡜᭷ពᕪࡣ࡞࠸ࡶࡢࡢ㧗࠸ഴྥ࡟࠶ࡗࡓࠋE)*) ⩌ࡣ s࡛࠶ࡾ &RQWURO ⩌࡟ẚ࡭᭷ព࡞పୗࡣㄆࡵࡎ㸪+\GURJHO ⩌࡜␗࡞ࡾ (ODVWDVHRQO\ ⩌࡟ẚ࡭࡚᭷ព࡟ቑຍࡋࡓࠋ մ Ș60$ 㝧ᛶ⣽⬊ࡢ๭ྜࡣ &RQWURO ⩌࡛ࡣ s࡛࠶ࡾ㸪࡟ (ODVWDVHRQO\ ⩌ࡢ s࡜ẚ㍑ࡋ ࡚᭷ព࡟ప࠿ࡗࡓࠋE)*) ⩌ࡣ㸪s࡛࠶ࡾ㸪(ODVWDVHRQO\ ⩌࡜ẚ㍑ࡋ࡚᭷ពᕪࡣぢࡽࢀ࡞࠿ࡗ ࡓࡶࡢࡢ㸪㧗࠸ഴྥࢆ♧ࡋࡓࠋ յ E)*) ⩌ࡣ (ODVWDVHRQO\ ⩌࡟ẚ࡭࡚᭷ព࡟㐃⥆ࡋࡓᖹᆒ཰⦰ຊࡢቑຍࢆㄆࡵࡓࠋ ն ᭱኱཰⦰ຊ࡟࠾࠸࡚ࡶ (ODVWDVHRQO\ ⩌࡟ẚ࡭ E)*) ⩌ࡣ᭷ព࡟㧗࠸཰⦰ຊࢆㄆࡵࡓࠋ ࠙⪃ᐹࠚ  ࣛࢵࢺື⬦⒗ࣔࢹࣝࢆ౑⏝ࡋࡓᮏᐇ㦂࡛ࡣ E)*) ࡢ⾑⟶෌⏕ຠᯝ࡟ࡼࡾ⤌⧊Ꮫⓗ࡟ᖹ⁥➽⣽⬊ࡢ෌⏕㸪ᙎᛶ ⧄⥔ࡢቑຍࡀ⸆๣㠀ᢞ୚⩌࡟ẚ࡭࡚ከ࠸ഴྥ࡟࠶ࡗࡓࡇ࡜ࡀ♧ࡉࢀࡓࠋື⬦⒗ᢚไࡀ♧ࡉࢀࡓ⩌࡟཰⦰ຊࡢ ᨵၿࡀ☜ㄆࡉࢀ㸪ື⬦⒗ቨ࡟ E)*) ࢆస⏝ࡉࡏࡿ஦࡛⾑⟶ቨࡢ⤌⧊Ꮫⓗ෌⏕ࡢࡳ࡞ࡽࡎ㸪ᶵ⬟ⓗ࡟ࡶ෌⏕ࡋ࠺ ࡿ஦ࡀ♧ࡉࢀࡓࠋ⮫ᗋⓗ࡞ື⬦⒗ࡣື⬦◳໬ᛶኚ໬ࢆకࡗ࡚࠾ࡾᐇ㦂ࣔࢹࣝࡢࡳ࡛ࡢホ౯࡟ࡣ㝈⏺ࡀ࠶ࡿࡀ㸪 ⸆๣ᢞ୚࡟ࡼࡿື⬦⒗ᣑ኱ᢚไ࡟ຍ࠼࡚཰⦰ຊࡢᨵၿ࡟ࡼࡾ◚⿣ࢆᢚไࡍࡿᶵ⬟ⓗᨵၿࡀ♧၀ࡉࢀࡿ⤖ᯝ࡛ ࠶ࡾ㸪௒ᚋప౵く἞⒪㸦⭡⭍㙾ୗ࡛ࡢᣑ኱⾑⟶࡬ࡢ⸆๣ᢞ୚࡟ࡼࡿ἞⒪ࡸ㸪⸆๣ᚎᨺᛶࢫࢸࣥࢺࢢࣛࣇࢺ἞ ⒪➼㸧࡬ࡢᑟධ࡞࡝ࡶᮇᚅ࡛ࡁࡿࡶࡢ࡛࠶ࡿ࡜⪃࠼ࡿࠋ ࠙⤖ㄽࠚ



E)*) ྵᾐ⏕≀ศゎᛶࣁ࢖ࢻࣟࢤࣝࢩ࣮ࢺࡢື⬦⒗⾑⟶࡬ࡢᢞ୚࡟ࡼࡾື⬦⒗ᣑ኱ᢚไࡀᚓࡽࢀ㸪ࡲࡓྠ᫬ ࡟ື⬦⒗ቨࡢ㍍ᗘࡢ཰⦰ຊࡢᨵၿࡀᚓࡽࢀࡓࠋື⬦⒗ቨࡀ⸆๣ᢞ୚࡟ࡼࡾᶵ⬟ⓗᨵၿࢆ♧ࡍ஦࡛◚⿣ࢆច㉳ ࡋ࠺ࡿ⾑ᅽ࡟⪏࠼ᚓࡿ஦ࡶ♧၀ࡉࢀ㸪ື⬦⒗ࡢ◚⿣ண㜵἞⒪ࡢⓎᒎ࡟ᐤ୚ࡍࡿྍ⬟ᛶࡀ♧၀ࡉࢀࡓࠋ