Title 乳牛におけるDifructose Anhydride (DFA) Ⅲの飼料添加が骨密度および骨代謝に及ぼす影響に関する研究( 本文(Fulltext) ) Author(s) 前谷, 文美 Report No.(Doctoral Degree) 博士(獣医学) 甲第580号 Issue Date 2021-03-15 Type 博士論文 Version ETD URL http://hdl.handle.net/20.500.12099/81624 ※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。
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ங∵࠾ࡅࡿ 'LIUXFWRVH$QK\GULGH ')$ Ϫࡢ㣫ᩱῧຍࡀ
㦵ᐦᗘ࠾ࡼࡧ㦵௦ㅰཬࡰࡍᙳ㡪㛵ࡍࡿ◊✲
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㐃ྜ⋇་Ꮫ◊✲⛉
㸦ᖏᗈ␆⏘Ꮫ㸧
๓㇂ᩥ⨾
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⥴ゝ ... 3 ➨Ϩ❶ Ἢஙᚋᮇࡢங∵ᑐࡍࡿDFAϪ⤥㣵ࡀ㦵ᐦᗘ࠼ࡿᙳ㡪 ... 7 㸯㸬ࡣࡌࡵ ... 8 㸰㸬ᮦᩱ᪉ἲ ... 8 㸱㸬⤖ᯝ ... 12 㸲㸬⪃ᐹ ... 13 㸳㸬ᑠᣓ ... 16 㸴㸬ᅗ⾲ ... 17 ➨ϩ❶ Ἢஙᚋᮇࡽศፔᚋࡲ࡛ࡢங∵ᑐࡍࡿ㛗ᮇࡢ DFAϪ⤥㣵ࡀ㦵࠾ࡼࡧ Ca ௦ㅰ ࠼ࡿᙳ㡪 ... 22 㸯㸬ࡣࡌࡵ ... 23 㸰㸬ᮦᩱ᪉ἲ ... 24 㸱㸬⤖ᯝ ... 27 㸲㸬⪃ᐹ ... 29 㸳㸬ᑠᣓ ... 33 㸴㸬ᅗ⾲ ... 35 ⥲ᣓ ... 45 ㅰ㎡ ... 48 ᘬ⏝ᩥ⊩ ... 492 ␎ ␎ㄒ୍ぴ 1,25-(OH)2D άᛶࣅࢱ࣑ࣥ D BAP 㦵ᆺࣝ࢝ࣜ࣍ࢫࣇࢱ࣮ࢮ BCS ࣎ࢹ࣭ࢥࣥࢹࢩ࣭ࣙࣥࢫࢥ BMD 㦵ᐦᗘ BW య㔜 Ca ࢝ࣝࢩ࣒࢘ CT ࢝ࣝࢩࢺࢽࣥ DCAD 㣫ᩱ୰㝧࢜ࣥ̿㝜࢜ࣥᕪ
DFA III ࢲࣇࣛࢡࢺ࣮ࢫࣥࣁࢻࣛࢻ III
DMI ≀ᦤྲྀ㔞 ECLIA 㟁ẼᏛⓎගච ᐃἲ ELISA 㓝⣲⤖ྜච྾╔ ᐃἲ ICP ㄏᑟ⤖ྜࣉࣛࢬ࣐ iP ↓ᶵࣜࣥ K ࣒࢝ࣜ࢘ Mg ࣐ࢢࢿࢩ࣒࢘ NTX I ᆺࢥ࣮ࣛࢤࣥᯫᶫ-N-ࢸࣟ࣌ࣉࢳࢻ OC ࢜ࢫࢸ࢜࢝ࣝࢩࣥ PTH ୖ⓶ᑠయ࣍ࣝࣔࣥ RA X ⥺ᙳ྾ගගᗘἲ TJ ࢱࢺࢪࣕࣥࢡࢩࣙࣥ ucOC ప࢝ࣝ࣎࢟ࢩࣝ࢜ࢫࢸ࢜࢝ࣝࢩࣥ TMR ΰྜ㣫ᩱ TRAP5b 㓇▼㓟⪏ᛶ㓟࣍ࢫࣇࢱ࣮ࢮ 5b
3
⥴
⥴ゝ
4 ங∵ࡣ⏘ḟࢆ㔜ࡡࡿࡈங㔞ࡀቑຍࡋ㸪㦵ᐦᗘࡀపୗࡍࡿࡇࡀሗ࿌ࡉࢀ ࡚࠸ࡿ[2㸪32㸪67]ࠋࡇࢀࡣ㸪ங∵ࡢἪஙྛᮇ࡛Ⓨ⏕ࡍࡿ࢝ࣝࢩ࣒࢘㸦Ca㸧௦ㅰ ືែ㉳ᅉࡍࡿࠋࡲࡎ㸪Ἢஙึᮇࡣங㔞ࡀᛴ⃭ቑຍࡍࡿࡇࡽ㸪⾑୰Ca ⃰ ᗘࡀపୗࡋࡸࡍ࠸[11]ࠋἪஙึᮇࡢங∵࡛ࡣ⾑୰ Ca ⃰ᗘࢆ⥔ᣢࡍࡿࡓࡵ㸪༑ ᣦ⭠ࡽࡢCa ྾࠾ࡼࡧᒀ⣽⟶ࡽࡢ Ca ྾ຍ࠼࡚㸪㦵྾ࡀάᛶ ࡍࡿ[11㸪58]ࠋḟ㸪Ἢஙᚋᮇࡽஙᮇࡣங㔞ࡀῶᑡࡘἪஙࡀṆࡍࡿࡇ ࡽ㸪⾑୰Ca ⃰ᗘࡀୖ᪼ࡋ㸪㦵ᙧᡂࡀάᛶࡍࡿ[2㸪21㸪32㸪67]ࠋ᭱ᚋ㸪 ศፔᚋࡣ㔞ࡢCa ࡀึஙฟࡉࢀ୍㐣ᛶ⾑୰ Ca ⃰ᗘࡀపୗࡍࡿࡢ࡛㸪㦵 ྾ࡀάᛶࡍࡿ[11㸪12]ࠋ௨ୖࡼࡾ㸪Ἢஙᚋᮇࡽஙᮇࡅ࡚㣫ᩱ Ca ࢆῧຍࡋከ⤥ࡍࡿࡇࡀ㦵ᐦᗘపୗࢆᢚไࡍࡿ♧၀ࡉࢀࡿࠋἪஙᚋᮇࡽ ஙᮇࡅ࡚࣒࢝ࣜ࢘㸦K㸧ࢆ㣫ᩱῧຍࡋ㸪㦵ᐦᗘࢆ ᐃࡋࡓሗ࿌ࡣᏑᅾࡍࡿ ࡀ[2]㸪Ἢஙᚋᮇࡽศፔࡲ࡛ࡢ㛗ᮇ㛫 Ca ࢆ㣫ᩱῧຍࡋ㸪ங∵ࡢ㦵ᐦᗘ್ࢆ ㄪᰝࡋࡓሗ࿌ࡣᏑᅾࡋ࡞࠸ࠋ ࣄࢺ࡛ࡣ㸪㛢⤒ᚋࡢ㧗㱋ዪᛶࡀ㦵ᐦᗘపୗࡼࡿ㦵⢒ࡋࡻ࠺ࢆⓎࡍࡿࡇ ࡀሗ࿌ࡉࢀ࡚࠸ࡿ[19]ࠋ㦵⢒ࡋࡻ࠺ࡣ㦵ᢡࢆᣍࡁࡸࡍ࠸ᝈ࡛࠶ࡿࡇࡽ㸪 ⒪ࡣࣅࢫࣇ࢛ࢫࣇ࢛ࢿ࣮ࢺ〇㸪ࢹࣀࢫ࣐ࣈ࠾ࡼࡧࣛࣟ࢟ࢩࣇ࢙ࣥ࡞ࡢ 㦵ᢡᢚไ⒪⸆ࡀ⏝ࡉࢀ࡚࠸ࡿࠋࡋࡋ㸪ࡇࢀࡽࡢ㦵ᢡᢚไ⒪⸆ࡣࡑࢀࡒࢀ స⏝ᶵᗎࡶ␗࡞ࡾ㸪⒪㛗ᮇ㛫ࢆ᭷ࡍࡿࡢ࡛㸪᪥㡭ࡽ㦵ᐦᗘపୗࢆ᭱ᑠ㝈 ᢚไࡍࡿ⏕άດࡵࡿࡇࡀ㔜せどࡉࢀ࡚࠸ࡿࠋࡋࡓࡀࡗ࡚㸪ᡂ㛗ᮇ㦵ᐦᗘࢆ 㧗ࡵࡿࡇࡀ㦵ᐦᗘపୗࢆ᭱ᑠ㝈ࡍࡿࡇ⧅ࡀࡾ[19]㸪ࡑࡢࡓࡵ᪥㡭ࡽ Ca ࢆ✚ᴟⓗᦤྲྀࡍࡿࡇࡀ᥎ዡࡉࢀ࡚࠸ࡿࠋ Ca ࡣ⚄⤒ࡢఏ㐩่⃭ࡸ㦵᱁➽࡞ࡽࡧᚰ➽ࡢ⦰่⃭㛵ࡍࡿ࣑ࢿ࡛ࣛࣝ ࠶ࡿ[33]ࠋ∵ࡢ༑ᣦ⭠࠾ࡅࡿ Ca ྾⤒㊰ࡋ࡚㸪⭠ୖ⓶⣽⬊ෆࢆࡍࡿ⬟ ື㍺㏦࡞ࡽࡧ⭠ୖ⓶⣽⬊㛫㝽ࢆࡍࡿཷື㍺㏦ࡢ2 ✀㢮ࡀᏑᅾࡍࡿ[3]ࠋ⬟ື ㍺㏦ࡣ⣽⬊㉁ෆࡢCa ⤖ྜࢱࣥࣃࢡ㉁㸦CaBP9K㸧ࡀ Ca ࢜ࣥ⤖ྜࡋ㸪ᇶᗏ
5 㒊⛣ືࡍࡿࡇ࡛ᡂ❧ࡍࡿࠋCaBP9K ࡣ 1,25㸫ࢪࣄࢻࣟ࢟ࢩࣅࢱ࣑ࣥ D㸦1,25-(OH)2D㸧ࡀୖ⓶⣽⬊ෆࡢ 1,25-(OH)2D ཷᐜయ⤖ྜࡍࡿࡇ࡛Ⓨ⌧ࡍࡿࠋࡋ ࡋ㸪ࣛࢵࢺ[57]࠾ࡼࡧ∵[23]࡛ࡣຍ㱋క࠸㸪1,25-(OH)2D ཷᐜయᩘࡀῶᑡࡍࡿ ࡇࡽ㸪⬟ື㍺㏦ࡼࡿCa ྾⬟ຊࡣపୗࡍࡿࠋ㧗㱋ࡢங∵ࡗ࡚ 1,25-(OH)2D ཷᐜయᩘࡢῶᑡࡣప Ca ⾑ࢆᣍࡁࡸࡍ࠸せᅉࡢ୍ࡘ࡛࠶ࡿࠋ୍᪉㸪ཷ ື㍺㏦ࡣ⭠⟶ෆ⾑ᾮ㛫ࡢ⃰ᗘ໙㓄ࢆ⏝ࡋࡓ༢⣧ᣑᩓ࡛࠶ࡿࡢ࡛㸪ຍ㱋ࡼ ࡿ1,25-(OH)2D ཷᐜయᩘῶᑡࡢᙳ㡪[18]ࢆཷࡅ࡞࠸Ⅼࡀ࠶ࡿࠋࡋࡋ㸪⣽⬊㛫 㝽Ꮡᅾࡍࡿᐦ╔⤖ྜ㸦ࢱࢺࢪࣕࣥࢡࢩࣙࣥ㸸TJ㸧ࡣ⭷ෆࢱࣥࣃࢡ㉁ࡼࡗ ࡚ᵓᡂࡉࢀ࡚࠸࡚㸪⣽⬊㛫ࢆᙉࡃ⤖ྜࡍࡿࣂ࡛ࣜ࠶ࡾ㸪ᑠศᏊ௨እࡢ≀㉁ࡢ⛣ ືࢆไ㝈ࡋ࡚࠸ࡿ[7]ࠋ
Difructose anhydride (di-D-fructofuranose-1,2’:2,3’-dianhydride: DFA)Ϫࡣ
ࣇࣛࢡࢺ࣮ࢫ 2 ศᏊࡀ⤖ྜࡋࡓ㞴ᾘᛶࡢ࢜ࣜࢦ⢾࡛࠶ࡿࠋࣛࢵࢺࡢᑠ⭠ࢆ⏝ ࠸ࡓin vitroヨ㦂࠾࠸࡚㸪DFAϪࡀᑠ⭠ୖ⓶⣽⬊㛫㝽ࡢ TJ స⏝ࡋ㸪⣽⬊㛫 㝽⤒㊰ࡽCa ࡢཷື྾ࢆಁ㐍ࡍࡿࡇࡀ☜ㄆࡉࢀ࡚࠸ࡿ[54]ࠋ∵ࡢin vitro ヨ㦂࠾࠸࡚ࡶ㸪ྠᵝ㸪DFAϪࡀ༑ᣦ⭠ୖ⓶⣽⬊㛫㝽ࡽࡢཷືⓗ࡞྾ࢆ ಁ㐍ࡋ㸪Ca ࡢ྾⋡ࢆቑຍࡉࡏࡿࡇࡀሗ࿌ࡉࢀ࡚࠸ࡿ[59]ࠋࡇࢀࡣ㸪DFAϪ ࡀ TJ ࡢᵓᡂࢱࣥࣃࢡ㉁࡛࠶ࡿࢡ࣮ࣟࢹࣥ 1 ࢡࢳࣥࣇ࣓ࣛࣥࢺࡢศᕸ ࢆኚࡉࡏ㸪⤒ୖ⓶㟁Ẽᢠࢆୗࡆࡿࡇࡼࡾ㸪⣽⬊㛫㏱㐣࣐࣮࣮࢝ࡢ⛣ືࢆ ಁ㐍ࡉࡏࡿࡓࡵ࡛࠶ࡿ[55]ࠋDFAϪࡣ㸪ࢳࢥࣜࡢ᰿࡞ྵࡲࢀࡿࢾࣜࣥࡀࣇ ࣝࢡࢩࣝࢺࣛࣥࢫࣇ࢙࣮ࣛࢮฎ⌮ࡉࢀ㸪ࣇࣛࢡࢺ࣮ࢫ2 ศᏊࡀ 2 ⟠ᡤ࡛ࣇࣝࢡ ࢺࢩࢻ⤖ྜࡍࡿࡇ࡛⏕ᡂࡉࢀࡿ[27㸪49]ࠋDFAϪࢆᦤྲྀࡍࡿ㸪ங㓟⳦࠾ࡼࡧ Bifidobacterium ᒓࡣ㈨ࡉࢀࡎ[37]㸪Ruminococcusᒓࡢࡳ㈨ࡉࢀࡿ≉ ᚩࢆᣢࡘ[38]ࠋங∵࠾࠸࡚ DFAϪࡣ➨୍⫶ᚤ⏕≀ࡼࡿศゎࢆཷࡅࡃ࠸ᛶ ㉁ࢆ᭷ࡍࡿࡇ[52]ࡀ▱ࡽࢀ࡚࠾ࡾ㸪ཤໃ∵⤒ཱྀᢞࡋࡓヨ㦂࡛ࡣ 2 㛫ᚋ ༑ᣦ⭠ෆ᳨࡛ฟࡉࢀ[41]㸪ங∵⤥㣵ࡋࡓヨ㦂࡛ࡣ 4 㛫ᚋᦤྲྀ㔞ࡢ⣙
6 70%ࡀ༑ᣦ⭠฿㐩ࡍࡿࡇ[59]ࡀ♧ࡉࢀ࡚࠸ࡿࠋศፔ๓ᚋங∵ࡢ DFAϪ ⤥㣵ヨ㦂࡛ࡣ㸪⭠⟶ࡽࡢCa ࡢཷື㍺㏦ࡢಁ㐍㉳ᅉࡋ࡚㸪ศፔᚋࡢ⾑୰ Ca ⃰ᗘࡀ᪩ᮇᅇࡋࡓࡇࡀ♧၀ࡉࢀࡓ[60]ࠋࡇࢀࡽࡢሗ࿌௨እࡶ㸪ฟ⏕Ꮚ∵ ᑐࡍࡿDFAϪࡢ⤒ཱྀᢞࡣึஙࡽࡢ IgG ྾ࢆ㧗ࡵ[51]㸪ฟ⏕Ꮚ∵ࡢᗣ ࢆᙉࡍࡿࡇࡀሗ࿌ࡉࢀ࡚࠸ࡿ[35㸪56]ࠋ ௨ୖࡼࡾ㸪ங∵ࡢἪஙᚋᮇࡽศፔ┤ᚋࡅ࡚ DFAϪࢆ㣫ᩱῧຍࡍࡿࡇ ࡣ㸪㦵࣑ࢿࣛࣝࢆቑຍࡉࡏ㸪ศፔ๓ᚋࡢCa ㈇Ⲵ≧ែ㸦ప Ca ⾑㸧ࢆ㍍ῶࡍࡿ ྍ⬟ᛶࡀ࠶ࡿ⪃࠼ࡓࠋࡋࡋ㸪ங∵ࡢἪஙᚋᮇ࡞ࡽࡧஙᮇ㦵࣑ࢿࣛࣝࢆ ቑຍࡉࡏࡿ㣫㣴ᢏ⾡㛵ࡍࡿᏛ⾡ሗࡣᑡ࡞ࡃ㸪Ἢஙᚋᮇࡽศፔ┤ᚋࡲ࡛㐃 ⥆ࡋࡓᮇ㛫ࡢCa ௦ㅰ㛵ࡍࡿ▱ぢࡶ᫂࡞Ⅼࡀከ࠸ࠋࡑࡇ࡛㸪ᮏ◊✲࡛ࡣ㸪Ἢ ஙᚋᮇ࡞ࡽࡧஙᮇ DFAϪࢆ㣫ᩱῧຍࡋࡓሙྜࡢ㦵࣑ࢿࣛࣝ㦵௦ㅰືែ ࢆ᫂ࡽࡍࡿࡇࢆ┠ⓗࡋ㸪➨I ❶࡛ࡣἪஙᚋᮇ∵ᑐࡍࡿ DFAϪ⤥㣵ࡀ 㦵ᐦᗘ㦵௦ㅰ࠼ࡿᙳ㡪ࡘ࠸࡚㸪➨II ❶࡛ࡣἪஙᚋᮇࡽศፔ┤ᚋ ࡅ࡚㛗ᮇ㛫ࢃࡓࡿங∵ࡢ DFAϪ⤥㣵ࡀ㦵௦ㅰ࠾ࡼࡧ Ca ௦ㅰ࠼ࡿᙳ㡪 ࡘ࠸᳨࡚ウࡋࡓࠋ
7
➨
➨Ϩ❶
Ἢஙᚋᮇࡢங∵ᑐࡍࡿ
DFAϪ⤥㣵ࡀ
8
11. ࡣࡌࡵ
Ἢஙึᮇࡢங∵ࡣங㔞ࡀᛴ⃭ቑຍࡍࡿࡇࡽ㸪⾑୰Ca ⃰ᗘࡀపୗࡋࡸࡍ ࠸ࠋ⾑୰Ca ⃰ᗘࢆ⥔ᣢࡍࡿࡓࡵ⏕యෆࡢᜏᖖᛶࡀస⏝ࡋ㸪༑ᣦ⭠ࡽࡢ Ca ྾㸪ᒀ⣽⟶ࡽࡢCa ྾ຍ࠼࡚㸪㦵྾ࡀάᛶࡍࡿࠋ୍᪉㸪Ἢஙᚋᮇ ࡽஙᮇࡅ࡚ࡢங∵࡛ࡣங㔞ࡀῶᑡࡍࡿࡇࡽ㸪⾑୰Ca ⃰ᗘࡀୖ᪼ࡋ ࡸࡍ࠸ࠋవࡢCa ࡣᒀ୰ฟࡉࢀ㸪㦵ᙧᡂࡀάᛶࡍࡿࠋࡲࡓ㸪ศፔᚋࡣἪ ங㛤కࡗ࡚ࡧ㦵྾ࡀάᛶࡍࡿ[11㸪12]ࠋங∵ࡣศፔࢆ㔜ࡡࡿࡈங 㔞ࡀቑຍࡋ㸪ୖグࡢࡼ࠺࡞Ca ௦ㅰࢆ⧞ࡾ㏉ࡋࡓ⤖ᯝ㸪㦵ᐦᗘࡀపୗࡍࡿ[2㸪32㸪 67]ࠋࡋࡓࡀࡗ࡚㸪Ἢஙᚋᮇ Ca ࢆከ⤥ࡋ㦵ࡢ࣑ࢿࣛࣝࢆቑຍ࡛ࡁࢀࡤ㸪ศፔ ᚋࡢ㦵ᐦᗘࡢῶᑡࢆ⦆࡛ࡁࡿ⪃࠼ࡽࢀࡿࠋࡑࡇ࡛ᮏ❶࡛ࡣ㸪Ἢஙᚋᮇࡢங∵ DFAϪࢆ⤥㣵ࡋࡓ㝿ࡢ㦵ᐦᗘ㦵௦ㅰࡢᙳ㡪ࢆ᳨ウࡋࡓࠋ2. ᮦᩱ࠾ࡼࡧ᪉ἲ
2-1 ౪ヨ∵࡞ࡽࡧ᥇ᮦィ⏬ ᾏ㐨ᖏᗈᕷ୍⯡㓗㎰ᐙ7 ㌺࡛㣫㣴ࡉࢀ࡚࠸ࡿἪஙᚋᮇዷፎ∵ 24 㢌㸦Ἢங᪥ ᩘ 199-319 ᪥㸪ዷፎ᪥ᩘ 131㹼157 ᪥㸧ࢆ౪ヨ∵ࡋ㸪⤥㣵㣫ᩱࡼࡾᑐ↷⩌ 㸦n=12㸧࠾ࡼࡧ DFA ⩌㸦n=12㸧ศࡅࡓࠋᑐ↷⩌ࡣ㸪ங㔞ࢆ 32㹼36 kg ⥔ᣢࡍࡿࡓࡵタィࡋࡓΰྜ㣫ᩱ㸦TMR㸧ࢆ⮬⏤᥇㣗ࡉࡏࡓࠋDFA ⩌ࡣ㸪 ྛ㎰ᐙ࡛ᑐ↷⩌ྠࡌ TMR ࡢ⮬⏤᥇㣗ຍ࠼࡚㸪DFAϪࢆ 20%ྵ᭷ࡍࡿ࣌ࣞ ࢵࢺ㸦᪥ᮏ⏓⳯〇⢾ᰴᘧ♫㸪ᮾி㸧ࢆ1 ᪥ᙜࡓࡾ 200g ῧຍࡋ࡚㸦DFAϪࡋ ࡚40 g㸧[59]㸪ヨ㦂㛤ጞ 1 ᪥┠ࡽ 28 ᪥㛫⥅⥆ⓗ⤥㣵ࡉࡏࡓࠋTable㸯 TMR ࡢ 1 ᪥ᙜࡓࡾࡢ Ca㸪ࣜࣥ㸦P㸧㸪࣐ࢢࢿࢩ࣒࢘㸦Mg㸧⤥㔞࡞ࡽࡧ Dietary cation-anion difference㸦DCAD㸧್[2]ࢆ♧ࡋࡓࠋ࡚ࡢ౪ヨ∵ࡣ㸪⋇་ᖌࡼ ࡿデ⒪ࢆせࡉࡎ㸪⮫ᗋⓗᗣ࡛࠶ࡗࡓࠋ࡞࠾㸪ᑐ↷⩌࠾ࡼࡧDFA ⩌ࡢ⏘ḟᩘ 㸦3.2 ± 0.1 ࠾ࡼࡧ 3.2 ± 0.1㸧㸪᭶㱋㸦50.8 ± 1.0 ࠾ࡼࡧ 49.1± 1.5㸧㸪య㔜㸦829 ±9 4.6 kg ࠾ࡼࡧ 829 ± 4.3 kg㸧㸪1 ᪥ங㔞㸦38.1 ± 0.6 kg ࠾ࡼࡧ 38.3 ± 0.66 kg㸧࡞ ࡽࡧ࣎ࢹࢥࣥࢹࢩࣙࣥࢫࢥ( BCS)[15]㸦3.29 ± 0.01 ࠾ࡼࡧ 3.29 ± 0.01㸧 ᭷ពᕪࡣࡳࡽࢀ࡞ࡗࡓࠋ࡚ࡢ౪ヨ∵ᑐࡋ࡚㸪㦵ᐦᗘ ᐃ㸪᥇⾑㸪᥇ᒀ࠾ ࡼࡧஙỒ᥇ྲྀࢆヨ㦂㛤ጞ᪥㸦0 ᪥㸧ࡽ 1 㐌㛫ẖ㸦0㸪7㸪14㸪21㸪28 ᪥┠㸧 ⾜ࡗࡓࠋᮏᐇ㦂ィ⏬ࡣᖏᗈ␆⏘Ꮫᐇ㦂ື≀ጤဨࡼࡾᢎㄆࡉࢀࡓ㸦㸡28-160㸧ࠋ 2-2 㦵ᐦᗘホ౯ 㦵ᐦᗘ ᐃࡣ㸪Keene ࡽ[26]࠾ࡼࡧ Maetani ࡽ[34]ࡢ᪉ἲᇶ࡙ࡁ X ⥺ᙳ ྾ගගᗘἲ㸦Radiographic Absorptiometry㸸RA㸧ࡼࡾ㸪ྑ୰ᡭ㦵➨ 4 ࠾ࡼ ࡧ 5 ᑿ᳝ࢆホ౯ᑐ㇟ࡋ࡚ᐇࡋࡓࠋ୰ᡭ㦵࠾ࡼࡧᑿ᳝ࡢᙳ᮲௳ࡣ㸪ࡑࢀࡒ ࢀ70 kV㸪1.0 mAs㸪↷ᑕ㊥㞳 70 cm ࡞ࡽࡧ 70 kV㸪0.5 mAs㸪↷ᑕ㊥㞳 70 cm ࡋࡓࠋᶆ‽ཧ↷యࡋ࡚࣑ࣝࢽ࣒࢘(Al)ࢫࢸࢵࣉ࢙࢘ࢵࢪࢆྠᙳࡋ㸪 ⏬ീࡢㄞྲྀࡣComputed Radiography㸦CR㸧⨨㸦FCR XL-2㸹ᐩኈࣇ࣒ࣝ㸪 ᮾி㸧ࢆ⏝ࡋࡓࠋࢹࢪࢱࣝ⏬ീࡣ⏬ീฎ⌮ࢯࣇࢺ࢙࢘(ImageJ㸹National Institute of Health, https:// imagej.nih.gov/ij/, 1997–2016)ྲྀࡾ㎸ࡳ㸪㛵ᚰ㡿 ᇦ㸦ROI㸧࠾ࡅࡿ㦵ᐦᗘࡢゎᯒࢆ⾜ࡗࡓࠋ୰ᡭ㦵ࡢ ROI ࡣ㸪㐲୰ᡭ⟶ࢆ୰ ᚰࡋ⓶㉁㦵ࢆྵࡴࡼ࠺タᐃࡋࡓ㸦Fig1-1a㸧ࠋᑿ᳝ࡢ ROI ࡣ㸪⓶㉁㦵࠾ࡼࡧ ᾏ⥥㦵ࢆྵࡴᑿ᳝యࡋࡓ㸦Fig1-1b㸧ࠋ୰ᡭ㦵ᑿ᳝ࡢ㦵ᐦᗘ್ࡣ㸪ྛ Al ࢫ ࢸࢵࣉཌ㸦3㸪6㸪9㸪12㸪15㸪18 mm㸧ࡢ ROI ࠾ࡅࡿ㦵ᐦᗘ್ࢆィ ࡋ㸪ࡑ ࡢ㦵ᐦᗘ್ྛAl ࢫࢸࢵࣉཌࡽ᳨㔞⥺ࢆసᡂࡍࡿࡇ࡛⟬ฟࡋࡓ[34]ࠋ 2-3 ⾑ᾮ⏕Ꮫゎᯒ ᥇⾑㸦⾑Ύ⏝8 mL㸪⾑₢⏝ 7 mL㸧ࡣ㸪᥇⾑⏝࣍ࣝࢲ࣮㸦࣋ࣀࢪ࢙ࢡࢺ II ࣍ ࣝࢲ࣮D㸪ࢸࣝࣔᰴᘧ♫㸪ᮾி㸧㸪᥇⾑㔪㸦࣋ࣀࢪ࢙ࢡࢺ II ᥇⾑㔪 S 21G㸪ࢸ ࣝࣔᰴᘧ♫㸪ᮾி㸧㸪⾑Ύ⏝┿✵᥇⾑⟶㸦ࣥࢭࣃࢵࢡϩ-D㸪ᚨᒣ✚Ỉᕤᴗᰴ
10 ᘧ♫㸪ᮾி㸧࠾ࡼࡧ⾑₢⏝┿✵᥇⾑⟶㸦࣋ࣀࢪ࢙ࢡࢺII ┿✵᥇⾑⟶ VP-H070K㸪 ࢸࣝࣔᰴᘧ♫㸪ᮾி㸧ࢆ⏝࠸࡚㢕㟼⬦ࡽ⾜ࡗࡓࠋ⾑ᾮࢧࣥࣉࣝࡣ4Υୗ࡛㐠 ᦙࡋ㸪37Υ㸪30 ศࡢ᮲௳࡛࣮ࣥ࢟ࣗ࣋ࢺࡋࡓࠋ᥇⾑ᚋ㸪1 㛫௨ෆ㐲ᚰศ 㞳㸦2,000g㸪10 ศ㛫㸧ࢆ⾜࠸㸪⾑Ύ⾑₢ࢆศ㞳ࡋࡓࠋ⾑Ύ࠾ࡼࡧ⾑₢ࡣゎ ᯒࡲ࡛෭ಖᏑ㸦-30Υ࡞ࡽࡧ-80Υ㸧ࡋࡓࠋ օ ⾑ΎCa ⃰ᗘࡢ ᐃ ⮬ື⾑ᾮ⏕Ꮫศᯒ⨨㸦AU680㸹࣋ࢵࢡ࣐ࣥࢥ࣮ࣝࢱ࣮㸪USA㸧ࢆ⏝࠸࡚㸪 ࣝࢭࢼࢰϪἲࡼࡾ ᐃࡋࡓࠋ ֆ ⾑Ύ㦵ᆺࣝ࢝ࣜࣇ࢛ࢫࣇࢱ࣮ࢮ㸦BAP㸧άᛶ್ࡢ ᐃ ᕷ㈍ࡢ࢟ࢵࢺ㸦Access Ostase㸹࣋ࢵࢡ࣐ࣥࢥ࣮ࣝࢱ࣮㸧ࢆ⏝࠸࡚㸪ᏛⓎග 㓝⣲ච ᐃἲ㸦CLEIA㸹chemiluminescent enzyme immunoassay㸧ࡼࡾ
ᐃࡋࡓࠋᮏ࢟ࢵࢺࡣ᳨య㸪☢ᛶ⢏Ꮚ⤖ྜᢠ࣐࢘ࢫ IgG ࣖࢠ࣏ࣜࢡࣟࢼ࣮ࣝᢠయ ࠾ࡼࡧᢠࣄࢺBAP ࣐࢘ࢫࣔࣀࢡࣟࢼ࣮ࣝᢠయࢆචᛂࡉࡏࡓᚋ㸪᭦࣑ࣝࢪ ࢙ࣥ4-࣓ࢺ࢟ࢩ-4-(3-ࣇ࢛ࢫࣇ࢙ࢺࣇ࢙ࢽࣝ)ࢫࣆࣟ [1,2-ࢪ࢜࢟ࢭࢱࣥ-3,2̓-ࢲ࣐ࣥࢱࣥ]ࢪࢼࢺ࣒ࣜ࢘ሷ㸦PPD㸧ࢆຍ࠼㓝⣲ᛂࡉࡏࡓࠋ࣑ࣝࢪ࢙ࣥ PPD ࡢศゎࡼࡿⓎග㔞ࡽ㸪᳨య୰ࡢBAP ⃰ᗘࢆ ᐃࡋࡓࠋ ᐃෆ㸦Intra-CV㸧 ࠾ࡼࡧ ᐃ㛫ኚືㄗᕪ㸦Inter-CV㸧ࡣࠊࡑࢀࡒࢀ 2.3㸣࠾ࡼࡧ 3.0%࡛࠶ࡗࡓࠋ և ⾑₢㦵ᆺ㓇▼㓟ᢠᛶ㓟ᛶࣇ࢛ࢫࣇࢱ࣮ࢮ5b㸦TRAP5b㸧άᛶ್ࡢ ᐃ ࢼࣇࢺ࣮ࣝ-ASBI-ࣜࣥ㓟㸦ග⣧⸆㸧ࢆᇶ㉁ࡋࡓ㓝⣲ᛂࡼࡿ⺯ග ᐃ ἲ[36㸪65]ࡼࡾ ᐃࡋࡓࠋ ֈ ⾑Ύప࢝ࣝ࣎࢟ࢩࣝ࢜ࢫࢸ࢜࢝ࣝࢩࣥ(ucOC)⃰ᗘࡢ ᐃ ᕷ㈍ࡢ࢟ࢵࢺ(Picolumi-ucOC㸹Eisai, Japan)ࢆ⏝࠸࡚㸪㟁ẼᏛⓎගච ᐃἲ㸦ECLIA㸧ࡼࡾ ᐃࡋࡓࠋᮏ࢟ࢵࢺࡣᢠ ucOC ᢠయ⤖ྜࣅ࣮ࢬࢆᅛ┦ ࡋ࡚㸪᳨య୰ࡢucOC ࢆࣅ࣮ࢬࣝࢸࢽ࣒࢘㸦Ru㸧ᶆ㆑ᢠ OC ᢠయ⤖ྜࡉࡏ ࡓᚋ㸪㟁ᴟୖ࡚㟁Ẽ࢚ࢿࣝࢠ࣮ࢆຍ࠼ࡿࡇ࡛⤖ྜࡋࡓRu ᶆ㆑ᢠ OC ᢠయ
11
㔞ᛂࡌ࡚Ru 㘒యࡀⓎගࡍࡿࠋⓎග㔞ࢆᶆ‽ᢠཎᾮࡢⓎග㔞ࢆᑐẚࡍࡿࡇ
᳨࡛య୰ࡢucOC ⃰ᗘࢆ ᐃࡋࡓࠋIntra-CV ࠾ࡼࡧ Inter-CV ࡣ 1.0%࠾ࡼࡧ 1.9%࡛࠶ࡗࡓࠋ
։ ⾑Ύ࢜ࢫࢸ࢜࢝ࣝࢩࣥ㸦OC㸧⃰ᗘࡢ ᐃ
ᕷ㈍ࡢ࢟ࢵࢺ㸦Elecsys㸹Roche Diagnostic, Switzerland)ࢆ⏝࠸࡚㸪ECLIA ἲࡼࡾ ᐃࡋࡓࠋᮏ࢟ࢵࢺࡣ᳨య㸪ࣅ࢜ࢳࣥᢠ OC ᢠయ࠾ࡼࡧࢺࣜࢫ Ru ᶆ㆑ᢠOC ᢠయࢆචᛂࡉࡏࡓᚋ㸪᭦ࢫࢺࣞࣉࢺࣅࢪࣥ㸦SA㸧ࢥ࣮ࢸ ࣥࢢ☢ᛶ࣐ࢡࣟࣃ࣮ࢸࢡࣝ㸦MP㸧ࢆຍ࠼࣮ࣥ࢟ࣗ࣋ࢺࡋࡓࠋᛂΰྜᾮ ࢆ྾ᘬࡋ㸪☢ຊࡼࡾSA ☢ᛶ MP ࢆ㟁ᴟᘬࡁࡘࡅ㸪SA ☢ᛶ MP ⤖ྜࡋ ࡓࢺࣜࢫRu ᶆ㆑ᢠ OC ᢠయࡢࢺࣜࢫ Ru ࡀⓎගࡍࡿࠋⓎග㔞ࢆᶆ‽ᢠཎᾮࡢ Ⓨග㔞ࢆᑐẚࡍࡿࡇ᳨࡛య୰ࡢOC ⃰ᗘࢆ ᐃࡋࡓࠋIntra-CV ࠾ࡼࡧ Inter-CV ࡣ 0.7%࠾ࡼࡧ 1.3%࡛࠶ࡗࡓࠋ ֊ ucOC/OC ẚࡢ⟬ฟ ucOC/OC ẚࡣ㸪ୖグࡢ᪉ἲ࡛ ᐃࡋࡓ ucOC ್࠾ࡼࡧ OC ್ࡼࡾ⟬ฟࡋࡓ [20]ࠋ 2-4 ங୰ Ca ⃰ᗘࡢศᯒ ᥇ᮦ᪥ࡢᮅࡢᦢஙᚋ㸪ࢫࣆࢵࢶ⟶(᪥Ỉ〇⸆ᰴᘧ♫㸪ᮾி)ஙỒ 10 mL ࢆ ᥇ྲྀࡋࡓࠋஙỒࢧࣥࣉࣝࡣ㸪ゎᯒࡲ࡛-30Υୗ࡛ಖᏑࡋࡓࠋ๓ฎ⌮ࡋ࡚㸪ࡿࡘ ࡰධࢀࡓஙࢧࣥࣉࣝ1 ml ࢭ࣮ࣝࣟࢫ㸦ග⣧⸆ᕤᴗᰴᘧ♫㸪㜰㸧ࢆ 0.5 g ຍ࠼ࡓࡶࡢࢆ㸪㟁Ẽ࣐ࢵࣇࣝ⅔㸦ࢻࣂࣥࢸࢵࢡᮾὒᰴᘧ♫㸪ᮾி㸧࡛ 600Υ㸪 2 㛫‵ᘧ⅊ࡋࡓࠋ⅊ᚋ㸪ሷ㓟࡛⁐ゎࡋ㸪㧗࿘Ἴㄏᑟ⤖ྜࣉࣛࢬ࣐Ⓨගศ ගศᯒἲ㸦ICPE-9000㸪ᓥὠ〇సᡤ㸪ி㒔㸧࡛ศᯒࡋࡓ[10]ࠋ 2-5 ᒀ⏕Ꮫศᯒ
12 ᒀ㐨࢝ࢸ࣮ࢸࣝ㸦ᐩኈᖹᕤᴗ㸪᪥ᮏ㸧ࢆ⏝࠸࡚ᑟᒀࢆ⾜࠸㸪ᒀࢆ᥇ྲྀࡋࡓࠋᒀ ࢧࣥࣉࣝࡣゎᯒࡲ࡛-30Υୗ࡛ಖᏑࡋࡓࠋ⮬ື⾑ᾮ⏕Ꮫศᯒ⨨㸦AU680㸧ࢆ ⏝࠸࡚㸪ᒀ୰Ca ⃰ᗘࡣࣝࢭࢼࢰϪἲ㸪ᒀ୰ࢡࣞࢳࢽࣥ㸦Cre㸧⃰ᗘࡣ㓝⣲ ἲࡼࡾ ᐃࡋ㸪ᒀ୰Ca/Cre ẚࢆ⟬ฟࡋࡓࠋ 2-6 ⤫ィᏛⓗゎᯒ
⤫ィᏛⓗゎᯒࡣSAS enterprise guide ver.7.1㸦SAS institute Inc.㸧ࢆ⏝ ࡋࡓࠋ ᐃ್ࡢ᥎⛣㛵ࡋ࡚㸪ᅛᐃຠᯝ㸦⩌㸪㛫㸪⩌㛫㸧㸪㓗㎰ᐙ࠾ࡼ ࡧ౪ヨ∵ࢆኚ㔞ຠᯝࡋࡓΰྜࣔࢹࣝࢆ⏝࠸࡚ ᐃศᩓศᯒࢆ⾜ࡗࡓࠋ᭷ ពᕪࡀぢࡽࢀࡓሙྜࡣ㸪Turkey ࡢከ㔜ẚ㍑᳨ᐃࡼࡾ⩌㛫࠾ࡼࡧ⩌ෆẚ㍑ࢆ⾜ ࡗࡓࠋ᭷ពỈ‽ࡣ5%ࡋࡓࠋ
33. ⤖ᯝ
Fig1̿2 ୰ᡭ㦵ᑿ᳝࠾ࡅࡿ㦵ᐦᗘࡢኚࢆ♧ࡋࡓࠋ୰ᡭ㦵ࡢ㦵ᐦᗘࡣ㸪 DFA ⩌࠾࠸࡚ 0 ᪥┠ẚ㍑ࡋ࡚ヨ㦂㛤ጞ 14㸪21 ࠾ࡼࡧ 28 ᪥┠᭷ពቑຍ ࡋࡓ㸦ࡑࢀࡒࢀP<0.01㸪P<0.05㸪P<0.001㸧ࠋ୍᪉㸪ᑐ↷⩌࠾࠸࡚୰ᡭ㦵ࡢ㦵 ᐦᗘࡣ7 ᪥┠࠾ࡼࡧ 14 ᪥┠୍㐣ᛶࡢ᭷ព࡞ቑຍࢆ♧ࡋࡓ㸦ࡑࢀࡒࢀP<0.001㸪 P<0.01㸧ࠋ➨ 4 ᑿ᳝ࡢ㦵ᐦᗘࡣ㸪DFA ⩌࠾࠸࡚ 0 ᪥┠ẚ㍑ࡋ࡚ 28 ᪥┠᭷ ពቑຍࡋ㸦P<0.01㸧㸪ᑐ↷⩌ࡼࡾ᭷ព࡞㧗್ࢆ♧ࡋࡓ㸦P<0.05㸧ࠋ➨ 5 ᑿ᳝ࡢ 㦵ᐦᗘࡣ㸪⩌ෆ࠾ࡼࡧ⩌㛫࡛ࡢ᭷ពᕪࡣ࡞ࡗࡓࠋFig1̿3 ⾑୰ࡢ Ca ⃰ᗘ㸪BAP ࠾ࡼࡧ TRAP5b άᛶ್㸪ucOC ࠾ࡼࡧ OC ⃰ᗘ࡞ࡽࡧucOC/OC ẚࡢ᥎⛣ࢆ♧ࡋࡓࠋ⾑୰ Ca ⃰ᗘ㸪⾑Ύ BAP ࠾ࡼࡧ⾑ ₢TRAP5b άᛶ್ࡣ㸪⩌ෆ࠾ࡼࡧ⩌㛫ࡢ᭷ពᕪࡣぢࡽࢀ࡞ࡗࡓࠋᑐ↷⩌ࡢ ⾑୰OC ⃰ᗘࡣ㸪0 ᪥┠ẚ㍑ࡋ࡚ 28 ᪥┠᭷ពῶᑡࡋࡓ㸦P<0.05㸧ࠋࡉࡽ ᑐ↷⩌ࡢ⾑୰ucOC ⃰ᗘࡣ㸪DFA ⩌ẚ㍑ࡋ࡚ 7㸪14 ࠾ࡼࡧ 21 ᪥┠᭷ព
13
࡞㧗್ࢆ♧ࡋࡓ㸦ࡑࢀࡒࢀP<0.01㸪P<0.05㸪P<0.05㸧ࠋDFA ⩌ࡢ ucOC/OC ẚ ࡣ㸪0 ᪥┠ẚ㍑ࡋ࡚ 21 ࠾ࡼࡧ 28 ᪥┠᭷ពῶᑡࡋ㸦ࡑࢀࡒࢀ P<0.01㸪
P<0.05㸧㸪ᑐ↷⩌ࡼࡾࡶ᭷ព࡞ప್ࢆ♧ࡋࡓ㸦ࡶP<0.001㸧ࠋ
Fig1̿4 ங୰ Ca ⃰ᗘ࡞ࡽࡧᒀ୰ Ca/Cre ẚࡢኚ⛣ࢆ♧ࡋࡓࠋDFA ⩌ࡢங ୰Ca ⃰ᗘࡣ 0 ᪥┠ࡼࡾ 28 ᪥┠᭷ពቑຍࡋ㸦P<0.05㸧㸪14㸪21 ࠾ࡼࡧ 28 ᪥┠ᑐ↷⩌ࡼࡾ᭷ព࡞㧗್ࢆ♧ࡋࡓ㸦ࡑࢀࡒࢀP<0.01㸪P<0.01㸪P<0.001㸧ࠋ ᒀ୰Ca/Cre ẚࡣ⩌ෆ࠾ࡼࡧ⩌㛫ࡢ᭷ពᕪࡣぢࡽࢀ࡞ࡗࡓࠋ
44. ⪃ᐹ
ᮏ❶࡛ࡣ㸪Ἢஙᚋᮇࡢங∵ᑐࡋ࡚28 ᪥㛫⥅⥆ⓗ DFAϪࢆ⤥㣵ࡋ㸪㦵ᐦᗘ ࡞ࡽࡧ㦵௦ㅰཬࡰࡍᙳ㡪ࡘ࠸᳨࡚ドࡋࡓࠋ ་⒪ศ㔝࡛ࡣ㸪㠀ほ⾑ⓗ㦵ᐦᗘࡢホ౯ἲࡋ࡚㸪ᮏ❶࡛⏝࠸ࡓRA ἲ௨እ㸪 㔜࢚ࢿࣝࢠ࣮㹖⥺྾ ᐃἲ㸦DXA㸧ࡸᐃ㔞ࢥࣥࣆ࣮ࣗࢱ࣮᩿ᒙἲ㸦QCT㸧 ࡀ⮫ᗋᛂ⏝ࡉࢀ࡚࠸ࡿ[9㸪14]ࠋRA ἲࡣ༢㠃✚ᙜࡓࡾࡢ㦵ᐦᗘ࡛⾲ࡉࢀࡿࡢ ᑐࡋ㸪QCT ἲࡣ༢య✚ᙜࡓࡾࡢ㦵ᐦᗘ࡛⾲ࡉࢀࡿࠋࡲࡓ㸪RA ἲࡣ୍✀㢮ࡢ X ⥺ࢆ⏝ࡍࡿࡇ࡛㦵ᐦᗘࢆ ᐃࡍࡿࡢᑐࡋ㸪DXA ἲࡣ✀㢮ࡢ X ⥺ࢆ ⏝ࡍࡿ[62]ࠋࡇࢀࡽࡢ≉ᚩࡽ RA ἲ࡛ ᐃࡋࡓ㦵ᐦᗘ್ࡣ㸪㦵ࡢయ✚㌾㒊⤌ ⧊ࡢᙳ㡪ࢆཷࡅࡿྍ⬟ᛶࡀ࠶ࡿࡀ[13]㸪DXA ἲ࡞ࡽࡧ QCT ἲᚲせ࡞⨨ ࢆ㸪୍⯡㓗㎰ᐙ࡛⏝ࡍࡿࡇࡣ⌧ᐇⓗ࡛ࡣ࡞࠸ࠋ୍᪉㸪RA ἲࡢᐇࡢࡓࡵ ࡣ㸪⨨ࢆᦠᖏࡋ㸪㎰ሙෆ࡛ᐇྍ⬟࡛࠶ࡿࡇࡽ㸪ᮏ◊✲࡛ࡣRA ἲࢆ㑅ᢥ ࡋࡓࠋDFA ⩌ࡢ➨ 4 ᑿ᳝࠾ࡼࡧ୰ᡭ㦵ࡢ㦵ᐦᗘ್ࡣ㸪0 ᪥┠ẚ㍑ࡋ࡚ 28 ᪥┠ ᭷ពቑຍࡋࡓࠋࡉࡽ➨5 ᑿ᳝ࡢ㦵ᐦᗘ್ࡶ 0 ᪥┠ẚ㍑ࡋ࡚ 28 ᪥┠ቑ ຍࡍࡿഴྥࢆ♧ࡋࡓ(P<0.1)ࠋ➨ 4 ᑿ᳝୰ᡭ㦵ࡢ㦵ᐦᗘ್ࡀྠቑຍࡋࡓࡇ ࡽ㸪DFAϪࡢ⤥㣵ࡀ㦵ࡢ࣑ࢿࣛࣝࢆቑຍࡉࡏࡓ♧၀ࡉࢀࡿࠋ㐣ཤࡢࣛࢵࢺ ࢆ⏝࠸ࡓ◊✲࠾࠸࡚ࡶ㸪༸ᕢฟᚋ DFAϪࢆ⤥ࡍࡿ⭣㦵ࡢ㦵ሷ㔞ࡀ14 ቑຍࡋࡓࡢሗ࿌[39]ࡸ DFAϪ⤥ᚋࡢ㐠ືࡼࡗ࡚⭣㦵࠾ࡼࡧ⬯㦵ࡢ㦵ሷ 㔞㦵ᐦᗘࡀቑຍࡋࡓࡢሗ࿌[53]ࡶ࠶ࡾ㸪DFAϪࡢ⤥㣵ࡀ㦵ࡢ࣑ࢿࣛࣝ✚ ࢆច㉳ࡋ㸪㦵ᐦᗘࢆቑຍࡉࡏࡓࡇࡀ᥎ᐹࡉࢀࡓࠋ ୍᪉㸪ᑐ↷⩌࡛ࡣ7 ࠾ࡼࡧ 14 ᪥┠࠾࠸࡚㸪DFA ⩌࡛ࡣ 14 ࠾ࡼࡧ 21 ᪥┠ ࠾࠸࡚୰ᡭ㦵ࡢ㦵ᐦᗘࡀ୍ⓗቑຍࡋࡓࠋࡋࡋ㸪ᑿ᳝ࡢ㦵ᐦᗘࡣ㸪୧⩌ ࡶ୰ᡭ㦵ࡢ㦵ᐦᗘࡀቑຍࡋࡓ᪥࠾࠸࡚᭷ព࡞ቑຍࡣぢࡽࢀ࡞ࡗࡓࠋங∵ ࡢ୰ᡭ㦵ࡣᑿ᳝ẚ㍑ࡋ࡚య✚ࡀࡁ࠸ࠋࡲࡓ RA ἲ࡛ ᐃࡋࡓ㦵ᐦᗘ್ࡣయ ✚ࡢᙳ㡪ࢆཷࡅࡸࡍ࠸ࡢ࡛㸪ᮏヨ㦂∵ࡢ7㸪14 ࠾ࡼࡧ 21 ᪥┠ࡢ୰ᡭ㦵ࡢ㦵ᐦᗘ ್ࡣ㸪㐣⟬ฟࡋࡓྍ⬟ᛶࡀ࠶ࡿ[13]ࠋࡋࡓࡀࡗ࡚㸪ᮏ❶࠾࠸࡚ RA ἲࡣᡂ ங∵ࡢ୰ᡭ㦵ẚ㍑ࡋ࡚ᑿ᳝ࡢ㦵ᐦᗘ ᐃ㐺ࡋ࡚࠸ࡓ⪃࠼ࡽࢀࡿࠋ 㦵ࡣ㦵ⱆ⣽⬊ࡼࡿ㦵ᙧᡂ◚㦵⣽⬊ࡼࡿ㦵྾ࡽᡂࡿ㦵௦ㅰᅇ㌿ࢆ⧞ ࡾ㏉ࡋ࡚࠸ࡿࠋ㦵ᙧᡂࡣ㦵ⱆ⣽⬊ࡢቑṪ࣭ศࡢ㐣⛬࡛㸪ቑṪᮇ㸪࣐ࢺࣜࢵࢡࢫ ᙧᡂᮇ࡞ࡽࡧ▼⅊ᮇศ㢮ࡉࢀ㸪ྛ㐣⛬ࡢ㦵≧ែࢆ≉␗ⓗᫎࡍࡿ⾑୰ ࡢ㦵ᙧᡂ࣐࣮࣮࢝ࡀ▱ࡽࢀ࡚࠸ࡿ[1]ࠋ୍᪉㸪⾑୰ࡢ㦵྾࣐࣮࣮࢝ࡋ࡚㸪◚ 㦵⣽⬊ࡽศἪࡉࢀࡿ㓝⣲ࡸ㦵ᇶ㉁ࡀ◚ቯࡉࢀࡿ㝿⏘⏕ࡉࢀࡿࢥ࣮ࣛࢤࣥᯫ ᶫࡢ᩿∦ࡀ▱ࡽࢀ࡚࠸ࡿ[1]ࠋᮏヨ㦂࡛ࡣ㦵௦ㅰືែࢆホ౯ࡍࡿࡓࡵ㸪RA ἲ ࡼࡿ㦵ᐦᗘࡢ ᐃ௨እ⾑୰ࡢ BAP㸪TRAP5b㸪OC ࠾ࡼࡧ ucOC ࠸ࡗࡓ㦵 ௦ㅰ࣐࣮࣮࢝ࡢ ᐃࡶ⾜ࡗࡓࠋBAP ࡣ㦵ⱆ⣽⬊ࡽ࣐ࢺࣜࢵࢡࢫᙧᡂᮇศἪ ࡉࢀࡿ㦵ᙧᡂ࣐࣮࣮࡛࢝࠶ࡿ[1㸪25㸪50]ࠋTRAP5b ࡣ◚㦵⣽⬊ࡢᩘࢆᫎࡍࡿ 㦵྾࣐࣮࣮࡛࢝࠶ࡿ[47]ࠋᮏ❶࠾࠸࡚㸪୧⩌ࡶ⾑୰ࡢ BAP ࠾ࡼࡧ TRAP5b άᛶ್᭷ព࡞⩌㛫࠾ࡼࡧ⩌ෆᕪࡣぢࡽࢀ࡞ࡗࡓࡓࡵ㸪DFA ࡣ◚㦵 ⣽⬊㦵ⱆ⣽⬊ࡢቑṪᙳ㡪ࢆ࠼࡞ࡗࡓࡇࡀ♧၀ࡉࢀࡓࠋ OC ࡣ▼⅊ᮇᡂ⇍ࡋࡓ㦵ⱆ⣽⬊࡛ྜᡂࡉࢀ㸪ࣅࢱ࣑ࣥ K ౫Ꮡᛶ࢝ࣝ࣎࢟ ࢩ࣮ࣛࢮࡢస⏝ࡼࡾࣁࢻࣟ࢟ࢩࣃࢱࢺᙉ࠸ぶᛶࢆ᭷ࡍࡿࡓࡵ[28㸪 40㸪43㸪44]㸪㦵ࡢᣦᶆࡉࢀࡿ[50]ࠋucOC ࡣ㦵⢒ࡋࡻ࠺ࡢᣦᶆࡋ࡚▱
15 ࡽࢀ[42]㸪ᡂ⇍㦵ⱆ⣽⬊ࡽ⾑୰ᨺฟࡉࢀࡿࠋࡲࡓ㸪ucOC ࡣ࢝ࣝ࣎࢟ࢩࣝ ࢆཷࡅࡿproOC ࡛࠶ࡿࡇࡽ㸪ucOC/OC ẚࡣࣅࢱ࣑ࣥ K ⃰ᗘࡢᣦᶆࡋ࡚ ⏝࠸ࡽࢀ࡚࠸ࡿ[40]ࠋᮏヨ㦂࡛ࡣ㸪ᑐ↷⩌࠾࠸࡚㸪⾑Ύ ucOC ⃰ᗘࡀ 7㸪14 ࠾ ࡼࡧ21 ᪥┠࠾࠸࡚ DFA ⩌ࡼࡾ᭷ព࡞㧗್ࢆ㸪⾑Ύ OC ⃰ᗘࡀ 0 ᪥┠ẚ ࡚28 ᪥┠᭷ព࡞పୗࢆ♧ࡋࡓࠋᑐ↷⩌࡛ࡣ ucOC ࡽ OC ࡢኚ⛣ࡀ㐍ࡲ࡞ ࡗࡓࡓࡵ㸪ᑐ↷⩌ࡢucOC/OC ẚࡀ 21 ᪥┠࠾ࡼࡧ 28 ᪥┠࠾࠸࡚㸪DFA ⩌ ࡼࡾࡶ᭷ព࡞㧗್ࢆ♧ࡋࡓ⪃࠼ࡽࢀࡓࠋࡲࡓDFA ⩌ࡢ OC ࠾ࡼࡧ ucOC ⃰ᗘ ࡀ⤒ⓗ᭷ព࡞ኚࢆ♧ࡉ࡞ࡗࡓࡀ㸪21 ࠾ࡼࡧ 28 ᪥┠࠾࠸࡚ ucOC/OC ẚࡀ0 ᪥┠ẚ㍑ࡋ࡚᭷ពపୗࡋࡓࠋ௨ୖࡢࡇࡽ㸪DFA ⩌࡛ࡣ㦵ⱆ⣽⬊ ෆ࡛proOC ࡛࠶ࡿ ucOC ࡽ OC ᐃᖖⓗኚࡉࢀ㸪OC ࡀ㦵ࡢ▼⅊ᇶ㉁
ྲྀࡾ㎸ࡲࢀ࡚࠸ࡓࡇࡀ⪃࠼ࡽࢀࡓࠋࡋࡓࡀࡗ࡚㸪DFA ⤥㣵ࡣ㦵ࡢ▼⅊ࢆ ಁ㐍ࡉࡏࡓ⪃࠼ࡽࢀࡓࠋࡋࡋ㸪ᮏ❶࡛ࡣ⾑୰ࡢࣅࢱ࣑ࣥK ⃰ᗘࡢ ᐃࢆ⾜ ࡗ࡚࠸࡞࠸ࡓࡵ㸪DFAϪ OC ศἪࡢ㛵ಀᛶࢆ᫂ࡽࡍࡿࡓࡵࡣ㸪ᚋ㸪 DFAϪࢆ⤥㣵ࡋࡓἪஙᚋᮇங∵ࡢࣅࢱ࣑ࣥ K ⃰ᗘࡢኚࢆ᫂ࡽࡍࡿࡇࡀ ᚲせ⪃࠼ࡽࢀࡓࠋ ᮏ❶ࡢヨ㦂࡛ࡣ㸪ᑐ↷⩌DFA ⩌ࡢ୧⩌࠾࠸࡚㸪⾑Ύ Ca ⃰ᗘ⩌㛫࠾ࡼ ࡧ⩌ෆࡢ᭷ពᕪࡣぢࡽࢀ࡞ࡗࡓࠋ⏕యࡣCa ᜏᖖᛶࢆ⥔ᣢࡋ㸪⾑୰ Ca ⃰ᗘ ࢆ୍ᐃಖࡘᶵᵓࡀᏑᅾࡍࡿࠋDFA ⩌࡛ࡣ Ca ࡀ༑ᣦ⭠࡛྾ಁ㐍ࡉࢀࡓࡀ㸪 ᜏᖖᛶࡼࡗ࡚⾑ΎCa ⃰ᗘࡀㄪᩚࡉࢀ࡚࠸ࡓࡇࡀ᥎ᐹࡉࢀࡓࠋ୍⯡ዷፎ∵ ࡀ㐣ᦤྲྀࡋࡓCa ࡣ㸪㦵㸪ᒀ㸪ங࠾ࡼࡧ⫾Ꮚ⛣⾜ࡍࡿ[46]ࠋᮏヨ㦂࡛㸪DFA ⩌ࡢᒀ୰ Ca/Cre ᭷ព࡞ኚࡀ࡞ࡗࡓࡶࢃࡽࡎ㸪ங୰ Ca ⃰ᗘࡣ 28 ᪥┠᭷ពቑຍࡋ㸪14㸪21 ࠾ࡼࡧ 28 ᪥┠࡛ࡣᑐ↷⩌ࡼࡾࡶ᭷ព㧗್࡛࠶ ࡗࡓࠋዷፎ190 ᪥┠௨ୗࡢங∵࡛ࡣ㸪⫾Ꮚᑐࡍࡿ Ca せồ㔞ࡣ 0 ➼ࡋ࠸ ⪃࠼ࡽࢀ࡚࠸ࡿ[22]ࠋ࡞࠾㸪౪ヨ∵ࡣヨ㦂ᮇ㛫୰㸪ዷፎ 190 ᪥┠௨ୗ࡛࠶ࡗࡓ 㸦ዷፎ159 ᪥㹼185 ᪥┠㸧ࠋ௨ୖࡢࡇࡽ㸪DFAϪࡼࡗ࡚༑ᣦ⭠࡛྾ಁ
16 㐍ࡉࢀࡓ㐣࡞Ca ࡣ㸪⭈⮚ࡼࡾࡶࡴࡋࢁங⭢࠾࠸࡚ฟࡉࢀࡓࡇࡀ᥎ᐹࡉ ࢀࡓࠋࡇࡢ⌧㇟ࡢヲ⣽࡞㐣⛬ࡘ࠸࡚ࡣ㸪ᮏヨ㦂࡛ࡣゎ࡛᫂ࡁ࡞ࡗࡓࡀ㸪୍ࡘ ࡢ᥎ᐹࡋ࡚࢝ࣝࢩࢺࢽࣥ㸦CT㸧ࡀ㛵ࡋ࡚࠸ࡓྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋCT ࡣ㧗 Ca 㣗ࡢᦤྲྀ⏥≧⭢ࡢ C ⣽⬊ࡽศἪಁ㐍ࡉࢀࡿ[8㸪33]ࠋCT ࡣ◚㦵⣽⬊ࡢ άືࢆᢚไࡋ㸪㦵ࡢCa ỿ╔ಁ㐍࡞ࡽࡧᒀฟࡍࡿ Ca 㔞ࢆቑຍࡉࡏࡿࡇ ࡛⾑୰Ca ⃰ᗘࢆㄪ⠇ࡍࡿ[33]ࠋ㦵ࡸ⭈⮚ CT ཷᐜయࡀᏑᅾࡍࡿࡇࡣ୍⯡ ⓗ࡛࠶ࡿࡢᑐࡋ㸪ங⭢ࡢ CT ཷᐜయ㛵ࡋ࡚ࡣዷፎࣛࢵࢺ࠾ࡅࡿሗ࿌ࡋ ぢᙜࡓࡽ࡞࠸[61]ࠋࡉࡽ∵࠾࠸࡚ங⭢ CT ཷᐜయࡀศᕸࡍࡿ࠸࠺㐣ཤࡢ ሗ࿌ࡀ࡞࠸ࠋ௨ୖࡢࡇࡽ DFAϪࢆᦤྲྀࡋࡓἪஙᚋᮇ∵ࡢ Ca ௦ㅰືែ㛵 ࡋ࡚᭦࡞ࡿㄪᰝࡀᚲせ⪃࠼ࡽࢀࡿࠋ ᮏ❶ࡢ⤖ㄽࡋ࡚㸪DFAϪࢆ 28 ᪥㛫Ἢஙᚋᮇ∵⤥㣵ࡋࡓ⤖ᯝ㸪㦵ࡢ▼⅊ ࡀಁ㐍ࡉࢀ㸪㦵ࡢ࣑ࢿࣛࣝࢆቑຍࡉࡏࡓࠋࡲࡓ DFAϪࡼࡗ࡚྾ಁ㐍ࡉࢀࡓ Ca ࡣங⭢ฟࡉࢀ㸪ங୰ Ca ⃰ᗘࢆቑຍࡉࡏࡓࠋ
55. ᑠᣓ
Ἢஙᚋᮇࡢங∵ᑐࡋ࡚ 28 ᪥㛫⥅⥆ⓗ DFAϪࢆ⤥㣵ࡋ㸪㦵ᐦᗘ࡞ࡽࡧ 㦵௦ㅰཬࡰࡍᙳ㡪ࡘ࠸᳨࡚ドࡋࡓࠋDFA ⩌࡛ࡣ㸪28 ᪥┠➨ 4 ᑿ᳝࡞ࡽࡧ ୰ᡭ㦵ࡢ㦵ᐦᗘࡢቑຍ ucOC/OC ẚࡢῶᑡࡀྠㄆࡵࡽࢀࡓࡇࡽ㸪 ucOC ࡽኚࡉࢀࡓ OC ࡀᐃᖖⓗ㦵ࡢ▼⅊ᇶ㉁ྲྀࡾ㎸ࡲࢀ㸪▼⅊ࡀಁ 㐍ࡋࡓ⤖ᯝ㸪㦵ࡢ࣑ࢿࣛࣝࡀቑຍࡋࡓ⪃࠼ࡽࢀࡓࠋࡲࡓ㸪DFAϪࡼࡗ࡚྾ ಁ㐍ࡉࢀࡓCa ࡀங⭢ฟࡉࢀ㸪ங୰ Ca ⃰ᗘࡀ 28 ᪥┠ቑຍࡍࡿ⪃࠼ࡽ ࢀࡓࠋ17
66. ᅗ⾲
Table1ʁ֦܊Ͷ͕͜ΖΩϩεΤϞʤCaʥɼໃؽϨϱʤPʥ͕Γ;ϜήϋεΤϞʤMgʥ ɻɻɻɻ1ೖͪΕڛڇྖͳDietary cation-anion difference (DCAD)1)
܊ Ca P Mg DCAD3) ʤg/kg DM2)ʥ ʤg/kg DM2)ʥ ʤg/kg DM2)ʥ (mEq/100g) DFA ʤn=12ʥ 10.9±0.23 5.1±0.32 2.5±0.07 16.2±0.9 ଲল ʤn=12ʥ 11.0±0.22 4.3±0.06 2.6±0.06 16.9±0.8 1ʥસͱฑۋ±ඬ६ޣࠫ 2ʥףྖ
18
22
➨
➨ϩ❶
Ἢஙᚋᮇࡽศፔᚋࡲ࡛ࡢங∵ᑐࡍࡿ㛗ᮇࡢ
DFAϪ⤥㣵ࡀ㦵࠾ࡼࡧ Ca ௦ㅰ࠼ࡿᙳ㡪
23
11. ࡣࡌࡵ
ዷፎ୰ࡢங∵࡛ࡣ༑ᣦ⭠࡛྾ࡉࢀࡓCa ࡣ⫾Ꮚ㸪ங㸪ᒀ㸪⣅࠾ࡼࡧ㦵⛣ ⾜ࡍࡿ[46]ࡀ㸪ዷፎ᪥ᩘࡼࡗ࡚⏕యෆࡢ Ca ௦ㅰ㸪ࡃ Ca ࡢ⤌⧊ࡢ⛣⾜ ≧ែࡣኚࡍࡿ⪃࠼ࡽࢀ࡚࠸ࡿࠋዷፎ 190 ᪥௨๓ࡢங∵ࡢయෆ࡛ࡣᾘ⟶࡛ ྾ࡉࢀࡓCa ࡢከࡃࡣங㸪ᒀ㸪⣅࠾ࡼࡧ㦵⛣⾜ࡍࡿࠋዷፎ 190 ᪥௨㝆ࡢங∵ ࡛ࡣங㸪ᒀ㸪⣅࠾ࡼࡧ㦵ຍ࠼ᚎࠎ⫾Ꮚࡶ⛣⾜ࡋጞࡵ[22]㸪ஙᮇࡣ⫾Ꮚ㸪 ᒀ㸪⣅࡞ࡽࡧ㦵ࡢ⛣⾜ࡀ࡞ࡿ[45㸪46]ࠋ➨Ϩ❶ࡢ౪ヨங∵ࡣዷፎ 190 ᪥ ௨๓ࡢἪஙᚋᮇ∵࡛࠶ࡾ㸪⫾Ꮚ౪⤥ࡉࢀࡿCa 㔞ࡣᑡ࡞࠸ࡓࡵ㸪DFAϪࡢ⤥㣵 ࡼࡾᾘ⟶࡛྾ࡉࢀࡓCa ࡣ㸪ங࠾ࡼࡧ㦵⛣⾜ࡋࡓ⪃࠼ࡽࢀࡓࠋࡉ ࡽ㸪Ἢஙᚋᮇࡽஙᮇࡅ࡚⥅⥆ⓗዷፎங∵ DFAᶛࢆ⤥㣵ࡍࡿ㸪 ձ㦵⛣⾜ࡍࡿCa 㔞ࢆቑࡸࡍࡇ࡛ศፔ๓⏝ྍ⬟࡞ Ca 㔞ࢆቑຍࡉࡏ㸪ղ ⏘ḟࡢቑຍࡶ㉳ࡁࡿࡉࢀࡿ㦵ᐦᗘࡢపୗ[2㸪32㸪67]ࢆ⦆ࡍࡿࡇࡶ ᮇᚅࡉࢀࡿࠋ⌧ᅾ㸪ศፔ๓⏕యෆ࡛⏝ྍ⬟࡞Ca 㔞ࢆቑຍࡉࡏࡿ㣫㣴ᢏ⾡ ࡋ࡚㸪ஙᚋᮇࡢ㣫ᩱ୰ࡢDCAD ್ㄪᩚ[2㸪11㸪30]㸪࣐ࢢࢿࢩ࣒࢘㸦Mgʥ[63] ࠾ࡼࡧ࣒࢝ࣜ࢘㸦K㸧[17]⃰ᗘࡢ㐺ṇ࡞ࡢᢏ⾡ࡀᗈࡃᬑཬࡋ࡚࠸ࡿࠋࡇࢀࡽ ࡢᢏ⾡ࡣ㸪⏕యෆࢆ௦ㅰᛶࢩࢻ࣮ࢩࢫ≧ែᑟࡃࡇ࡛㦵྾࡞ࡽࡧᒀ ⣽⟶ࡽࡢ Ca ྾ࢆάᛶࡍࡿ࠸ࡗࡓ࣓ࣜࢵࢺ[18㸪48]ࡀ࠶ࡿ୍᪉࡛㸪 DCAD ್ㄪᩚ⏝ࡍࡿ㝜࢜ࣥሷࡢႴዲᛶࡀపࡃ㸪ప Ca ⾑ᑐࡍࡿຠᯝ ࡀ༑ศⓎࡉࢀ࡞࠸[30]ࡢࢹ࣓ࣜࢵࢺࡶᏑᅾࡍࡿࠋศፔ๓ᚋ࠾ࡅࡿங∵ ࡢ DFAᶛ⤥㣵ࡀ Ca ௦ㅰཬࡰࡍຠᯝࢆ᳨ウࡋࡓ㐣ཤࡢሗ࿌࡛ࡣ㸪ศፔ┤ᚋࡢ ⾑୰ Ca ⃰ᗘࡣపୗࡋࡓ[60]ࠋࡇࡢ⌧㇟ࡣஙᚋᮇࡢ㣫ᩱࡀ㧗 DCAD ್࡛㸪ศ ፔࡢ㦵྾ࡀᢚไࡉࢀࡓࡓࡵ࡛࠶ࡿ⪃࠼ࡽࢀࡓࠋ௨ୖࡢࡇࡽ㸪Ἢஙᚋᮇ ࡽศፔࡲ࡛㛗ᮇࡢDFAᶛࡢ㣫ᩱῧຍࢆ⾜࠸࡞ࡀࡽ㸪ஙᚋᮇ㣫ᩱࡢ DCAD ್ ࢆ㐺ṇ⠊ᅖㄪᩚࡍࡿࡇࡀ㸪ศፔங∵ࡢ⏝ྍ⬟࡞Ca 㔞ࡢቑຍ⧅ࡀࡿ⪃ ࠼ࡽࢀࡿࠋᮏ❶࡛ࡣ㸪ங∵ᑐࡋ࡚Ἢஙᚋᮇࡽศፔࡲ࡛ࡢ㛗ᮇࢃࡓࡿ DFA24 Ϫࡢ㣫ᩱῧຍஙᚋᮇ㣫ᩱࡢDCAD ್ࡢ㐺ṇㄪᩚࢆ⾜࠸㸪ヨ㦂ᮇ㛫୰ࡢ㦵࠾ ࡼࡧCa ௦ㅰࡢኚࢆゎᯒࡋࡓࠋ
22. ᮦᩱ࠾ࡼࡧ᪉ἲ
2-1 ౪ヨ∵࡞ࡽࡧ᥇ᮦィ⏬ ᾏ㐨ᖏᗈᕷ୍⯡㓗㎰ᐙ࡛㣫㣴ࡉࢀ࡚࠸ࡿ࣍ࣝࢫࢱࣥ✀Ἢஙᚋᮇዷፎ∵16 㢌㸦Ἢங᪥ᩘ㸸211ʛ420 ᪥㸪ዷፎ᪥ᩘ 157㹼160 ᪥ʥࢆ౪ヨ∵ࡋ㸪⤥㣵㣫ᩱ ࡼࡾᑐ↷⩌㸦n = 8㸧࠾ࡼࡧ DFA ⩌㸦n = 8㸧↓సⅭࡾศࡅࡓࠋᑐ↷⩌ ࠾࠸࡚㸪ἪஙᮇࡣἪஙᮇ⏝TMR ࡢ⮬⏤᥇㣗ࡋ㸪ங๓ᮇࡣஙᮇ⏝ TMR ࡢ⮬⏤᥇㣗ஙᮇ⏝㓄ྜ㸦2 kg/ᅇ㸧ࡢ⤥㣵ࢆ⾜ࡗࡓࠋஙᚋᮇࡣஙᮇ⏝ TMR ⮬⏤᥇㣗ஙᮇ⏝㓄ྜ㸦4 kg/ᅇ㸧ࢆ࠼㸪ศፔᚋ 7 ᪥㛫ࡣἪஙᮇ⏝ TMR ࢳࣔࢩ࣮ⲡࡢ⮬⏤᥇㣗ࡋࡓ㸦Table2㸧ࠋDFA ⩌ࡣ㸪ᮇࡶᑐ↷⩌ྠࡌ 㣫ᩱෆᐜ㸪➨Ϩ❶ྠᵝ㸪DFAϪࢆ 20%ྵ᭷ࡍࡿ࣌ࣞࢵࢺ㸦᪥ᮏ⏓⳯〇⢾ᰴ ᘧ♫㸪ᮾி㸧ࢆ1 ᪥ᙜࡓࡾ 200 g ῧຍࡋ࡚㸦DFAϪࡋ࡚ 40 g㸧[59]㸪ศፔ ணᐃ119 ᪥๓ࡽศፔ 7 ᪥ᚋࡲ࡛⥅⥆ⓗ⤥㣵ࡉࡏࡓࠋஙᚋᮇࡢ DCAD ್ㄪ ᩚࡣ㸪◲㓟࣐ࢢࢿࢩ࣒࢘㸦㤿ᒃᡂᕤᴗᰴᘧ♫㸪᪥ᮏ㸧ࢆ⏝ࡋࡓࠋᑐ↷⩌ ࠾ࡼࡧDFA ⩌ࡢศፔ๓⏘ḟᩘ㸦3.25 ± 0.05 ࠾ࡼࡧ 3.00㸧㸪ᖺ㱋㸦3.87 ± 0.04 ࠾ ࡼࡧ3.5 ± 0.06㸧㸪య㔜㸦611 ± 4.49 kg ࠾ࡼࡧ 587 ± 2.7 kg㸧㸪1 ᪥ங㔞㸦40.3 ± 0.48 kg ࠾ࡼࡧ 41.0 ± 0.52 kg㸧࡞ࡽࡧ BCS [15]㸦3.19 ± 0.01 ࠾ࡼࡧ 3.19 ± 0.01㸧᭷ពᕪࡣ࡞ࡗࡓࠋ࡚ࡢ౪ヨ∵ᑐࡋ࡚㸪᥇⾑࠾ࡼࡧ᥇ᒀࢆศፔணᐃ ᪥ࡢ120㸪90㸪60㸪30㸪7 ᪥๓ศፔᙜ᪥㸪ศፔᚋ 24 㛫࠾ࡼࡧ 7 ᪥⾜ࡗࡓࠋ ศፔᙜ᪥࠾ࡼࡧศፔ24 㛫ᚋ௨እࡢ᥇⾑ࡣ᥇㣗ᚋ㸪ศፔᙜ᪥ࡣ⫾Ꮚፔฟᚋ 6 㛫௨ෆ㸪ศፔ24 㛫ᚋࡣ⫾Ꮚፔฟᚋࡽ 22㹼24 㛫ᚋࡋࡓࠋศፔ┤ᚋศ ፔ 12 㛫ᚋ㸪Ca ⿵⤥ࢆ┠ⓗࣜࣥ㓟 Ca ࢆ 100 g㸦Ca ࡋ࡚ 27 g㸧⤒ཱྀ ᢞࡋࡓࠋ25 2-2 ⾑ᾮ⏕Ꮫゎᯒ ᥇⾑㸦8 mL㸧ࡣ㸪᥇⾑⏝࣍ࣝࢲ࣮㸦࣋ࣀࢪ࢙ࢡࢺ II ࣍ࣝࢲ࣮D㸪ࢸࣝࣔᰴᘧ ♫㸪ᮾி㸧㸪᥇⾑㔪㸦࣋ࣀࢪ࢙ࢡࢺϩ᥇⾑㔪 S 21G㸪ࢸࣝࣔᰴᘧ♫㸪ᮾி㸧 ࠾ࡼࡧ⾑Ύ⏝┿✵᥇⾑⟶㸦ࣥࢭࣃࢵࢡϩ-D㸪ᚨᒣ✚Ỉᕤᴗᰴᘧ♫㸪ᮾி㸧ࢆ ⏝࠸࡚㸪ᑿ㟼⬦ࡼࡾ⾜ࡗࡓࠋ᥇ྲྀ⾑ᾮࡣ㸪➨Ϩ❶ྠᵝ㸪࣮ࣥ࢟ࣗ࣋ࢺᚋ㐲 ᚰศ㞳㸦2,000g㸪10 ศ㛫㸧ࢆ⾜࠸㸪⾑Ύࢆศ㞳ࡋࡓࠋ⾑Ύࡣゎᯒࡲ࡛-30Υ ୗ࡛෭ಖᏑࡋࡓࠋ օ ⾑ΎCa㸪↓ᶵࣜࣥ㸦iP㸧࠾ࡼࡧ Mg ⃰ᗘࡢ ᐃ ➨Ϩ❶ྠᵝ⮬ື⾑ᾮ⏕Ꮫศᯒ⨨㸦AU680㸪࣋ࢵࢡ࣐ࣥࢥ࣮ࣝࢱ࣮㸪 USA㸧ࢆ⏝࠸࡚ ᐃࡋࡓࠋ⾑Ύ iP ⃰ᗘ Mg ⃰ᗘࡣ㓝⣲ἲࡼࡾ㸪Ca ⃰ᗘ ྠᵝ⮬ື⾑ᾮ⏕Ꮫศᯒ⨨ࢆ⏝࠸࡚ ᐃࡋࡓࠋ ֆ ⾑ΎucOC ⃰ᗘࡢ ᐃ ➨Ϩ❶ࡢ᪉ἲࢆ⏝࠸࡚ ᐃࢆ⾜ࡗࡓࠋ և ⾑ΎOC ⃰ᗘࡢ ᐃ ➨Ϩ❶ࡢ᪉ἲࢆ⏝࠸࡚ ᐃࢆ⾜ࡗࡓࠋ ֈ ⾑ΎϨᆺࢥ࣮ࣛࢤࣥᯫᶫࢸࣟ࣌ࣉࢳࢻ㸦TypeϨcollagen cross-linked N-telopeptide, NTx㸧ࡢ ᐃ ᕷ㈍ࡢ࢟ࢵࢺ㸦Osteomark NTx Serum㸪࣮࣓ࣜࢹ࢝ࣝᰴᘧ♫㸪ᮾ ி 㸧 ࢆ ⏝ ࠸ ࡚ 㸪 ➇ ྜ 㓝 ⣲ ⤖ ྜ ච ྾ ╔ ᐃ ἲ 㸦ELISA㸸 Enzyme-linked immunosorbent assay㸧ࡼࡾ ᐃࡋࡓࠋᮏ࢟ࢵࢺࡣ࠶ࡽࡌࡵᅛ┦ࡉࢀࡓ NTx ᢠయᑐࡋ㸪᳨య୰ࡢ NTx ࣌ࣝ࢜࢟ࢩࢲ࣮ࢮࡼࡾᶆ㆑ࡉࢀࡓᢠయࢆ ຍ࠼㸪චᛂࢆ㸦25Υࠊ90 ศ㸧ࡉࡏࡓࠋⓎⰍᇶ㉁㸦Tetramethylbenzidine㸧 ࢆචᛂ⤊5 ศ๓ῧຍࡋ㸪30 ศ㛫ᛂᚋ㸪㏿ࡸ 450 nm ࡢ྾ගᗘ ᐃࡼࡾ࣌ࣝ࢜࢟ࢩࢲ࣮ࢮάᛶࢆ᳨ฟࡋ㸪᳨య୰ࡢ NTx ⃰ᗘࢆ⟬ฟࡋࡓࠋ
26 Intra-CV ࠾ࡼࡧ Inter-CV ࡣ 6.2%࠾ࡼࡧ 4.0%࡛࠶ࡗࡓࠋ ։ ucOC/OC ẚࡢ⟬ฟ ➨Ϩ❶ࡢ᪉ἲྠᵝ⟬ฟࡋࡓࠋ ֊ OC/NTx ẚࡢ⟬ฟ OC/NTx ẚࡣ㸪ୖグࡢ᪉ἲ࡛ ᐃࡋࡓ OC ್࠾ࡼࡧ NTx ್ࡼࡾ⟬ฟࡋࡓ [66]ࠋ ⾑Ύ⥲ࢥࣞࢫࢸ࣮ࣟࣝ㸦T-Cholesterol, T-cho㸧⃰ᗘࡢ ᐃ ⮬ື⾑ᾮ⏕Ꮫศᯒ⨨㸦AU680㸹࣋ࢵࢡ࣐ࣥࢥ࣮ࣝࢱ࣮㸪USA㸧ࢆ⏝࠸࡚㸪 ࢥࣞࢫࢸ࣮ࣟࣝ࢜࢟ࢩࢲ࣮ࢮἲࡼࡾ ᐃࡋࡓࠋ 2-3 ᒀ⏕Ꮫศᯒ ➨Ϩ❶ྠᵝࡢ᪉ἲ࡛᥇ྲྀࡋ㸪ᒀࡣ-30Υୗ࡛ಖᏑࡋࡓࠋ➨Ϩ❶ྠᵝ㸪 ᒀ୰Ca ⃰ᗘ Cre ⃰ᗘࢆ ᐃᚋ㸪ᒀ୰ Ca/Cre ẚࢆ⟬ฟࡋࡓࠋ 2-4 ࣮࣓ࣝࣥࣇࣝࢫࢥ㸦RFS㸧ࡢ ᐃ Burfeind ࡽ[4]ࡢ᪉ἲᇶ࡙࠸࡚ RFS ࢆࢫࢥࡋࡓࠋᮏ❶࡛ࡣ RFS ࡢྛ ࢫࢥ㸦1 ࡽ 5㸧≧ែࢆ 1.0 ้ࡳ࡛ࢫࢥࡋ㸪5 ẁ㝵࡛ࢫࢥࣜࣥࢢࡋࡓࠋ 2-5 ⤫ィᏛⓗゎᯒ
⤫ィᏛⓗゎᯒࡣSAS enterprise guide ver.7.1㸦SAS institute Inc.㸧࡞ࡽࡧ JMP15.1.0㸦SAS Institute Japan ᰴᘧ♫, ᮾி㸧ࢆ⏝ࡋࡓࠋ࡞࠾㸪ங∵ ࡢ⏕యෆࡢCa ࡢ⤌⧊⛣⾜≧ែࡣዷፎ᪥ᩘ㸪Ἢங࠾ࡼࡧஙࡢᙳ㡪ࢆཷࡅࡿ[22㸪 45㸪46]⪃࠼ࡽࢀࡿࡇࡽ㸪ୗグࡢ㏻ࡾヨ㦂ᮇ㛫ࢆ୕ᮇ㛫ศࡅ࡚⤫ィᏛⓗ ゎᯒࢆ⾜ࡗࡓࠋ
27 㹼60 ᪥๓㸧࠾ࡼࡧᮇ㛫 III㸦ศፔணᐃ 60 ᪥๓㹼ศፔ 7 ᪥ᚋ㸧ศࡅ࡚⤫ィᏛⓗ ゎᯒࢆ⾜ࡗࡓࠋᮇ㛫I ࠾ࡼࡧ II ࡢ ᐃ್ࡘ࠸࡚㸪Shapiro-Wilk normal ᳨ᐃ ࡼࡿṇつᛶࡢ☜ㄆᚋ㸪⩌ෆẚ㍑ࢆ Paired t ᳨ᐃ࠶ࡿ࠸ࡣ Wilcoxon 㡰᳨ ᐃࡼࡾ㸪⩌㛫ẚ㍑ࢆStudent t᳨ᐃ࠶ࡿ࠸ࡣMann-Whitney U ᳨ᐃࡼࡾ⾜ ࡗࡓࠋᮇ㛫 III ࡢ ᐃ್ࡘ࠸࡚ࡣ㸪ᅛᐃຠᯝ㸦⩌㸪㛫㸪⩌㛫㸧㸪౪ヨ∵ ࡞ࡽࡧἪஙࢫࢸ࣮ࢪࢆኚ㔞ຠᯝࡋࡓΰྜࣔࢹࣝࢆ⏝࠸࡚ ᐃศᩓศᯒ ࢆ⾜࠸㸪᭷ពᕪࡀぢࡽࢀࡓሙྜTurkey ࡢከ㔜ẚ㍑᳨ᐃࡼࡿ⩌㛫࠾ࡼࡧ⩌ෆ ẚ㍑ࢆ⾜ࡗࡓࠋྛ⤫ィฎ⌮࠾ࡅࡿ᭷ពỈ‽ࡣ5%ࡋࡓࠋ
33. ⤖ᯝ
օ ᮇ㛫I ࠾ࡅࡿ᥎⛣ Fig2̿1 ⾑୰ Ca㸪P ࠾ࡼࡧ Mg ⃰ᗘࡢ᥎⛣ࢆ♧ࡋࡓࠋ୧⩌࠾࠸࡚⾑୰ Ca ࠾ࡼࡧP ⃰ᗘࡣ⩌ෆ࠾ࡼࡧ⩌㛫࡛ࡢᕪࡣ࡞ࡗࡓࠋDFA ⩌ࡢ⾑୰ Mg ⃰ᗘࡣ㸪 ᑐ↷⩌ẚ㍑ࡋ࡚ศፔணᐃ120 ࠾ࡼࡧ 90 ᪥๓᭷ព࡞㧗್ࢆ♧ࡋࡓ㸦P<0.05㸧ࠋFig2̿2 ⾑୰ OC㸪NTx㸪OC/NTx ẚ㸪ucOC ࠾ࡼࡧ ucOC/OC ẚࡢ᥎⛣ࢆ ♧ࡋࡓࠋ⾑୰ OC ࠾ࡼࡧ ucOC ⃰ᗘࡣ⩌ෆ࠾ࡼࡧ⩌㛫ࡢ᭷ពᕪࡣぢࡽࢀ࡞ ࡗࡓࠋ⾑୰NTx ⃰ᗘࡣ㸪୧⩌ࡶศፔணᐃ 120 ᪥๓ẚ㍑ࡋ࡚ศፔணᐃ 90 ᪥๓᭷ពῶᑡࡋࡓ㸦ࡑࢀࡒࢀP<0.05㸪P<0.01㸧ࠋDFA ⩌ࡢ OC/NTx ẚࡣ㸪 ศፔணᐃ120 ᪥๓ẚ㍑ࡋ࡚ศፔணᐃ 90 ᪥๓᭷ពቑຍࡋࡓ㸦P<0.01㸧ࠋศ ፔணᐃ90 ᪥๓ࡢ ucOC/OC ẚࡣ㸪ᑐ↷⩌ࡼࡾࡶ DFA ⩌ࡢ᪉ࡀ᭷ព㧗್࡛࠶ ࡗࡓ㸦P<0.05㸧ࠋ
Fig2̿3 ⾑୰ T-cho ⃰ᗘ㸪ᒀ୰ Ca/Cre ẚ࠾ࡼࡧ RFS ࡢ᥎⛣ࢆ♧ࡋࡓࠋศ ፔணᐃ 120 ᪥๓ࡢ⾑୰ T-cho ⃰ᗘࡣᑐ↷⩌ࡼࡾࡶ DFA ⩌ࡢ᪉ࡀ᭷ព㧗್࡛ ࠶ࡗࡓ㸦P<0.01㸧ࠋᒀ୰ Ca/Cre ẚ࠾ࡼࡧ RFS ࡣ㸪⩌ෆ࠾ࡼࡧ⩌㛫࡛ࡢ᭷ពᕪ ࡣぢࡽࢀ࡞ࡗࡓࠋ
28 ֆ ᮇ㛫II ࠾ࡅࡿ᥎⛣
Fig2̿4 ⾑୰ Ca㸪P ࠾ࡼࡧ Mg ⃰ᗘࡢ᥎⛣ࢆ♧ࡋࡓࠋࡇࢀࡽࡢ㡯┠ࡣ㸪 ⩌ෆ࠾ࡼࡧ⩌㛫ࡢ᭷ពᕪࡣぢࡽࢀ࡞ࡗࡓࠋ
Fig2̿5 ⾑୰ OC㸪NTx㸪OC/NTx ẚ㸪ucOC ࠾ࡼࡧ ucOC/OC ẚࡢ᥎⛣ࢆ ♧ࡋࡓࠋ⾑୰OC㸪NTx㸪OC/NTx ẚ࠾ࡼࡧ ucOC ⃰ᗘࡣ⩌ෆ࠾ࡼࡧ⩌㛫࡛ࡢ ᭷ពᕪࡣぢࡽࢀ࡞ࡗࡓࠋศፔணᐃ 90 ᪥๓ࡢ ucOC/OC ẚࡣ㸪ᑐ↷⩌ࡼࡾࡶ DFA ⩌ࡢ᪉ࡀ᭷ព㧗್࡛࠶ࡗࡓ㸦P<0.05㸧ࠋ
Fig2̿6 ⾑୰ T-cho ⃰ᗘ㸪ᒀ୰ Ca/Cre ẚ࠾ࡼࡧ RFS ࡢ᥎⛣ࢆ♧ࡋࡓࠋ⾑ ୰T-cho ⃰ᗘ࠾ࡼࡧ RFS ࡣ㸪⩌ෆ࠾ࡼࡧ⩌㛫࡛ࡢ᭷ពᕪࡣ࡞ࡗࡓࠋᑐ↷⩌ ࡢᒀ୰Ca/Cre ẚࡣ㸪ศፔணᐃ 90 ᪥๓ẚ㍑ࡋ࡚ศፔணᐃ 60 ᪥๓᭷ពቑ ຍࡋࡓ㸦P㸺0.05㸧ࠋ
և ᮇ㛫III ࠾ࡅࡿ᥎⛣
Fig2̿7 ⾑୰ Ca㸪P ࠾ࡼࡧ Mg ⃰ᗘࡢ᥎⛣ࢆ♧ࡋࡓࠋDFA ⩌࠾࠸࡚㸪ศ ፔᙜ᪥ࡢ⾑୰Ca ⃰ᗘࡣศፔணᐃ 60 ᪥๓ࡽศፔணᐃ 7 ᪥๓ࡢᮇ㛫ẚ㍑ࡋ࡚ ᭷ពῶᑡ㸦P<0.001㸧ࡋࡓࡀ㸪ศፔ 7 ᪥ᚋ᭷ពୖ᪼ࡋࡓࠋᑐ↷⩌࠾࠸࡚㸪 ศፔᙜ᪥ࡢ⾑୰Ca ⃰ᗘࡣศፔணᐃ 60 ᪥๓ࡽศፔணᐃ 7 ᪥๓ࡢᮇ㛫ẚ㍑ࡋ ࡚᭷ពῶᑡ㸦P<0.001㸧ࡋ㸪ศፔ 24 㛫ᚋ᭷ពୖ᪼ࡋࡓࠋ࡞࠾㸪ศፔᙜ ᪥ࡢ⾑୰Ca ⃰ᗘࡣ㸪ᑐ↷⩌ࡼࡾࡶ DFA ⩌ࡢ᪉ࡀ᭷ព㧗್࡛࠶ࡗࡓ㸦P<0.01㸧ࠋ ୧⩌ࡶ㸪⾑୰P ࠾ࡼࡧ Mg ⃰ᗘࡣ⩌ෆ࠾ࡼࡧ⩌㛫ࡢᕪࡣ࡞ࡗࡓࠋ
Fig2̿8 ⾑୰ OC㸪NTx㸪OC/NTx ẚ㸪ucOC ࠾ࡼࡧ ucOC/OC ẚࡢ᥎⛣ࢆ ♧ࡋࡓࠋ୧⩌ࡶ㸪ࡇࢀࡽࡢ㡯┠ࡣ⩌ෆ࠾ࡼࡧ⩌㛫ࡢᕪࡣぢࡽࢀ࡞ࡗࡓࠋ Fig2̿9 ⾑୰ T-cho ⃰ᗘ㸪ᒀ୰ Ca/Cre ẚ࠾ࡼࡧ RFS ࡢ᥎⛣ࢆ♧ࡋࡓࠋDFA ⩌࠾࠸࡚㸪⾑୰T-cho ⃰ᗘࡣศፔணᐃ 60 ᪥๓ẚ㍑ࡋ࡚ศፔணᐃ 30 ᪥๓
29 ᭷ព࡞ῶᑡࢆ♧ࡋࡓ㸦P<0.001㸧ࠋࡲࡓ㸪ศፔᙜ᪥࠾ࡼࡧศፔ 24 㛫ᚋࡣ㸪⾑ ୰T-cho ⃰ᗘࡣศፔணᐃ 30 ᪥๓ẚ㍑ࡋ࡚᭷ពῶᑡࡋࡓ㸦P<0.05㸧ࠋᑐ↷⩌ ࠾࠸࡚㸪⾑୰T-cho ⃰ᗘࡣศፔணᐃ 60 ᪥๓ẚ㍑ࡋ࡚ศፔணᐃ 30 ᪥๓᭷ ពῶᑡࡋࡓ㸦P<0.001㸧ࠋࡲࡓ㸪ศፔᙜ᪥࠾ࡼࡧศፔ 24 㛫ᚋࡣ㸪⾑୰ T-cho ⃰ᗘࡣศፔணᐃ 30 ᪥๓ẚ㍑ࡋ࡚᭷ពῶᑡࡋࡓ㸦P<0.05㸧ࠋᒀ୰ Ca/Cre ẚ࠾ࡼࡧRFS ࡣ㸪୧⩌ࡶ⩌ෆ࠾ࡼࡧ⩌㛫ࡢᕪࡣ࡞ࡗࡓࠋ
4. ⪃ᐹ
ᮏ❶࡛ࡣἪஙᚋᮇࡽศፔࡲ࡛㛗ᮇࡢ DFAϪ⤥㣵ࢆ⾜࠸㸪ங∵ࡢ㦵௦ㅰ࠾ࡼ ࡧCa ௦ㅰ࠼ࡿᙳ㡪ࡘ࠸᳨࡚ドࡋࡓࠋங⇕ࡢ༴㝤ᅉᏊࡋ࡚㸪ရ✀㸪ᖺ㱋㸪 㣫ᩱ୰Ca ࠾ࡼࡧ K ⃰ᗘ㸪㣫ᩱ୰ DCAD ್࡞ࡽࡧప Mg ⾑࡞ࡀᣲࡆࡽࢀ ࡿ[6㸪17]ࠋᮏ౪ヨ∵ࡢရ✀㸪ᖺ㱋ᕪࡣ࡞ࡃ㸪ࡲࡓᮏヨ㦂ࡢ㣫ᩱ୰ࡢ Ca ࠾ࡼࡧ K ⃰ᗘ㸪㣫ᩱ୰ࡢ DCAD ್ࡣྠ୍㣫ᩱ࡛࠶ࡗࡓࡢ࡛ᕪࡣ࡞ࡗࡓ⪃࠼ࡽࢀࡿࠋ ࡉࡽヨ㦂ᮇ㛫୰ࡢ୧⩌ࡢ⾑୰ Mg ⃰ᗘ᭷ពᕪࡣぢࡽࢀ࡞ࡗࡓࠋࡋࡓࡀࡗ ࡚ᮏヨ㦂࡛ࡣࡇࢀࡽࡢ༴㝤ᅉᏊࡣᑐ↷⩌DFA ⩌㛫࡛᭷ពᕪࡀ࡞ࡃ㸪⩌㛫ࡢ┦ 㐪ⅬࡣDFAϪ⤥㣵ࡢ᭷↓࡛࠶ࡗࡓ⪃࠼ࡽࢀࡓࠋ ᮏ❶࡛ࡣ㸪➨Ϩ❶ྠᵝ㦵௦ㅰືែࢆホ౯ࡍࡿࡓࡵ㸪⾑୰ࡢ OC㸪ucOC ࠾ࡼࡧNTx ࠸ࡗࡓ㦵௦ㅰ࣐࣮࣮࢝ࡢ ᐃࡶ⾜ࡗࡓࠋNTx ࡣ㦵྾ࡢ㝿⏘⏕ ࡉࢀࡿϨᆺࢥ࣮ࣛࢤࣥᯫᶫࡢN ࢸࣟ࣌ࣉࢳࢻ࡛࠶ࡾ㸪㦵≉␗ᛶࡢ㧗࠸㦵྾࣐ ࣮࣮࡛࢝࠶ࡿ[1]ࠋOC/NTx ẚࡣ㦵ᙧᡂ࣐࣮࣮࢝㦵྾࣐࣮࣮࢝ࡢẚ࡛࠶ࡾ㸪 㦵௦ㅰືែࢆデ᩿ࡍࡿࡓࡵ⏝ࡉࢀ࡚࠸ࡿ[66]ࠋ ᮇ㛫Ϩ㸦ศፔணᐃ120 ᪥๓㹼90 ᪥๓㸧ࡢゎᯒ࠾࠸࡚㸪ᑐ↷⩌࠾ࡼࡧ DFA ⩌ ࡢศፔணᐃ 90 ᪥๓ࡢ⾑୰ NTx ⃰ᗘࡣ 120 ᪥๓ẚ㍑ࡋ࡚᭷ពῶᑡࡋࡓࠋ DFA ⩌ࡢศፔணᐃ 90 ᪥๓ࡢ OC/NTx ẚࡣ 120 ᪥๓ẚ㍑ࡋ࡚᭷ពቑຍࡋࡓ ࡀ㸪⾑୰OC ⃰ᗘࡣ᭷ព࡞ኚࢆ♧ࡉ࡞ࡗࡓࠋOC ࡣᡂ⇍ࡋࡓ㦵ⱆ⣽⬊࡛ྜᡂ30
ࡉࢀࡿ㦵ᙧᡂ࣐࣮࣮࡛࢝࠶ࡿ[28㸪50]ࠋNTx ࡣ㦵≉␗ᛶࡢ㧗࠸㦵྾࣐࣮࣮࢝ ࡛࠶ࡾ㸪CT ࡼࡗ࡚ไᚚࡉࢀ࡚࠸ࡿ[1]ࠋCT ࡣ㧗 Ca 㣗ࡢᦤྲྀศἪࡉࢀ[8㸪 33]㸪◚㦵⣽⬊ࡢάືࢆᢚไࡍࡿࠋᅇ㸪⾑୰ CT ⃰ᗘࡢ ᐃࡣ⾜ࡗ࡚࠸࡞࠸ࡀ㸪 ౪ヨ∵ࡣᮇ㛫I ࠾࠸࡚ Ca ࢆせồ㔞௨ୖᦤྲྀࡋ࡚࠸ࡓࡓࡵ㸪CT ࡢศἪಁ㐍 ࡼࡿ㦵྾ࡢᢚไࡀ᥎ᐹࡉࢀࡓࠋࡉࡽ㸪DFA ⩌࡛ࡣ DFA III ᦤྲྀࡼࡿ Ca ࡢ྾ಁ㐍[60]ࡶ㔜࡞ࡾ㸪㦵ᙧᡂࡀඃ࡞ࡗࡓࡇࡀ♧၀ࡉࢀࡓࠋ ୍᪉㸪୧⩌ࡶศፔணᐃ120 ᪥๓㹼90 ᪥๓ࡢ⾑୰ OC ࠾ࡼࡧ ucOC ⃰ᗘ ⩌ෆࡢ᭷ពᕪࡣぢࡽࢀ࡞ࡗࡓࡀ㸪DFA ⩌ࡢศፔ 90 ᪥๓ࡢ ucOC/OC ẚࡀᑐ↷ ⩌ࡼࡾ᭷ព࡞㧗್ࢆ♧ࡋࡓࠋucOC ࡣࣅࢱ࣑ࣥ K ౫Ꮡᛶ࢝ࣝ࣎࢟ࢩ࣮ࣛࢮࡢస ⏝ࢆཷࡅࡿproOC ࡋ࡚㸪OC ࡣࣅࢱ࣑ࣥ K ౫Ꮡᛶ࢝ࣝ࣎࢟ࢩ࣮ࣛࢮࡢస⏝ᚋ Ț-࢝ࣝ࣎࢟ࢩࣝ OC ࡋ࡚ࡶᡂ⇍㦵ⱆ⣽⬊ࡽ⾑୰ᨺฟࡉࢀࡿ[40㸪 43]ࠋDFA ⩌࡛ࡣ ucOC ࠾ࡼࡧ OC ࡢศἪࡣ୍ᐃ࡛࠶ࡗࡓࡀ㸪ᑐ↷⩌ẚ㍑ࡋ࡚ ucOC ࡽ OC ࡢኚ⛣ࡀ㐍ᒎࡋ࡞ࡗࡓࡇࡀ⪃࠼ࡽࢀࡿࠋⱄື≀࡛ࡣࣅࢱ ࣑ࣥK ࡣ➨୍⫶ࡢ⣽⳦ྀࡼࡗ࡚ྜᡂࡉࢀ[5]㸪ୗ⑩ࡸࢩࢻ࣮ࢩࢫ➼ࡼࡾ⣽ ⳦ྀࡢኚࡍࡿሙྜせồ㔞ࢆ‶ࡓࡍࣅࢱ࣑ࣥK ࡢྜᡂࡀ㞴ࡋࡃ࡞ࡿࠋࡋࡓࡀ ࡗ࡚㸪DFA ⩌࡛ࡣఱࡢཎᅉ࡛ ucOC ࡽ OC ࡢኚᚲせ࡞ࣅࢱ࣑ࣥ K ࡢ ྜᡂࡀᅔ㞴࡞ࡗࡓࡇࡀ♧၀ࡉࢀࡓࡀ㸪ᚋ㸪DFAϪࢆ⤥㣵ࡋࡓἪஙᚋᮇங∵ ࡢ⾑୰ࣅࢱ࣑ࣥK ⃰ᗘࡢኚࡶేࡏ᳨࡚ドࡍࡿᚲせࡀ࠶ࡿ⪃࠼ࡽࢀࡓࠋ ᮇ㛫I ࠾࠸࡚㸪ᑐ↷⩌࠾ࡼࡧ DFA ⩌ࡢᒀ୰ Ca/Cre ẚ⩌ෆ࠾ࡼࡧ⩌㛫ࡢ ᭷ពᕪࡣぢࡽࢀ࡞ࡗࡓࠋዷፎ∵ࡀᦤྲྀࡋࡓCa ࡣ㸪㦵㸪ᒀ㸪ங࠾ࡼࡧ⫾Ꮚ⛣ ⾜ࡍࡿ[46]ࡀ㸪ᮇ㛫Ϩࡢ౪ヨ∵ࡣዷፎ 160 ᪥ࡽ 190 ᪥┠࡛࠶ࡾࠊ⫾Ꮚ⛣⾜ ࡍࡿCa ࡣࡰ↓ど࡛ࡁࡿࡇࡽ㸪ᾘ⟶྾ࡉࢀࡓ Ca ࡢከࡃࡣ㦵⛣⾜ࡋ ࡓࡇࡀ♧၀ࡉࢀࡓࠋ ᮇ㛫ϩ㸦ศፔணᐃ90 ᪥๓㹼60 ᪥๓㸧ࡢゎᯒ࠾࠸࡚㸪୧⩌ࡶ⾑୰ OC㸪 ucOC ࠾ࡼࡧ NTx ⃰ᗘ㸪OC/NTx ẚ⩌㛫࠾ࡼࡧ⩌ෆᕪࡣぢࡽࢀ࡞ࡗࡓࡀ㸪
31 ศፔணᐃ90 ᪥๓ࡢ ucOC/OC ẚࡣᑐ↷⩌ࡼࡾࡶ DFA ⩌ࡢ᪉ࡀ᭷ព࡞㧗್ࢆ♧ ࡋࡓࠋศፔணᐃ90 ᪥๓࠾࠸࡚ DFA ⩌࡛ࡣఱࡢཎᅉ࡛ ucOC ࡽ OC ࡢ ኚᚲせ࡞ࣅࢱ࣑ࣥ K ࡢྜᡂࡀᅔ㞴࡞ࡗ࡚࠸ࡓࡀ㸪ศፔணᐃ 60 ᪥๓࠾ ࠸࡚㸪ࡑࡢཎᅉࡀゎᾘࡉࢀ㸪ucOC ࡽ OC ࡢኚᚲせ࡞ࣅࢱ࣑ࣥ K ࡢྜ ᡂࡀྍ⬟࡞ࡗࡓ♧၀ࡉࢀࡓࠋ ᑐ↷⩌ẚ㍑ࡋ࡚ᒀ୰Ca/Cre ẚ࠾࠸࡚⩌㛫ᕪࡣぢࡽࢀ࡞ࡗࡓࡀ㸪ᑐ↷⩌ ࡛ࡣศፔணᐃ60 ᪥๓ࡢᒀ୰ Ca/Cre ẚࡣ 90 ᪥๓ࡼࡾ᭷ពቑຍࡋࡓࠋங∵ࡢ యෆ࡛ࡣ㸪ศፔணᐃ90 ᪥๓ࡽங⛣⾜ࡍࡿ Ca 㔞ࡣῶᑡࡋ㸪⫾Ꮚ⛣⾜ࡍࡿ Ca 㔞ࡣ⤒ⓗቑຍࡍࡿ[22]ࠋࡋࡓࡀࡗ࡚㸪ᑐ↷⩌࡛ࡣᾘ⟶྾ࡉࢀࡓ Ca ࡀ ங⛣⾜ࡍࡿྜࡀῶᑡࡋ㸪ᒀฟࡢྜࡀቑ࠼ࡓࡇࡀ᥎ᐹࡉࢀࡓࠋ୍᪉㸪 DFA ⩌࡛ࡣᾘ⟶྾ࡉࢀࡓ Ca ࡢከࡃࡀ⫾Ꮚ⛣⾜ࡋ㸪㦵ᒀ⛣⾜ࡍࡿ㔞 ࡀῶᑡࡋࡓࡇࡀ᥎ᐹࡉࢀࡓࠋ ᮇ㛫Ϫ㸦ศፔணᐃ60 ᪥๓㹼ศፔ 7 ᪥ᚋ㸧ࡢゎᯒ࠾࠸࡚㸪୧⩌ࡶศፔண ᐃ60 ᪥๓ࡽศፔ┤๓ࡲ࡛ࡢ⾑୰ Ca ⃰ᗘ⩌㛫࠾ࡼࡧ⩌ෆࡢ᭷ពᕪࡣぢࡽࢀ ࡞ࡗࡓࠋDFA ⩌࡛ࡣ Ca ࡀ༑ᣦ⭠࡛྾ಁ㐍ࡉࢀࡓࡀ㸪⏕యෆࡢᜏᖖᛶ ࡼࡗ࡚⾑୰Ca ⃰ᗘࡀㄪᩚࡉࢀࡓࡇࡀ♧၀ࡉࢀࡓࠋศፔᙜ᪥ࡢ⾑୰ Ca ⃰ᗘࡣ ୧⩌ࡶ᭷ពపୗࡋࡓࡀ㸪DFA ⩌ࡢ⾑୰ Ca ⃰ᗘࡣᑐ↷⩌ẚ㍑ࡋ࡚᭷ព ࡞㧗್ࢆ♧ࡋࡓࠋDCAD ࡣ㝜࢜ࣥሷࡢ⤥࡛ங∵ࡢ⏕యෆࢆ௦ㅰᛶࢩࢻ࣮ ࢩࢫ≧ែᑟࡁ㸪ྛჾᐁࡢୖ⓶ᑠయ࣍ࣝࣔࣥ㸦PTH㸧ཷᐜయࡢᛂᛶࢆྥୖࡉࡏ ࡿࡇ࡛㸪⏕యෆࡢCa 㔞ࢆቑຍࡉࡏࡿ[18]ࠋࡇࡢ⏕యෆࡢࢩࢻ࣮ࢩࢫ≧ែࢆ ☜ㄆࡍࡿ᪉ἲࡋ࡚㸪ᒀ pH ࡢ ᐃࡀ࠶ࡆࡽࢀࡿ[30]ࠋஙᚋᮇ㣫ᩱࡢ DCAD ್ࡀ-5㹼5 mEq/100 g ࡢሙྜ㸪ᒀ pH ࡣ 6.8ࠥ7.0 ሗ࿌ࡉࢀ࡚࠸ࡿ[31]ࡀ㸪ศፔ ணᐃ7 ᪥๓࠾ࡅࡿᒀ pH ್ࡣᑐ↷⩌࠾ࡼࡧ DFA ⩌࡛ࡑࢀࡒࢀ㸪6.93 s 0.05 ࠾ࡼࡧ6.78 s 0.06 ࡛࠶ࡗࡓࠋࡋࡓࡀࡗ࡚㸪ศፔணᐃ 7 ᪥๓ࡢ౪ヨ∵ࡣ DCAD ࡼࡗ࡚௦ㅰᛶࢩࢻ࣮ࢩࢫ≧ែᑟࢀ࡚࠸ࡓࡇࡀ᥎ᐹࡉࢀࡓࠋ㐣ཤ
32 ங∵DFAϪࢆ⤥㣵ࡋࡓヨ㦂࡛ࡣ㸪⤥㣵 1 㛫ᚋࡽ 12 㛫ᚋࡲ࡛ DFAϪࡀ ༑ᣦ⭠ෆ᳨࡛ฟࡉࢀࡓࡇࡀሗ࿌ࡉࢀ࡚࠸ࡿ[59]ࡀ㸪ᮏヨ㦂࡛ࡣ㸪DFA ⩌ ᑐࡋ࡚1 ᪥ 2 ᅇ DFAϪࢆ⤥㣵ࡋ࡚࠸ࡓࠋࡋࡓࡀࡗ࡚㸪DFA ⩌࡛ࡣ DCAD ࡼ ࡿຠᯝຍ࠼࡚ DFAϪࡀ Ca ࢆ྾ಁ㐍ࡉࡏࡓ⤖ᯝ㸪ᑐ↷⩌ẚ㍑ࡋ࡚᭷ព࡞ 㧗್ࢆ♧ࡋࡓ⪃࠼ࡽࢀࡓࠋ୍᪉㸪ᑐ↷⩌ࡢศፔᙜ᪥ࡢ⾑୰Ca ⃰ᗘࡣ㍍ᗘࡢప Ca ⾑࡛࠶ࡗࡓ㸦6.7 s 0.1 mg/dL㸧ࡀ㸪ங⇕Ⓨ∵ࡣ࡞ࡗࡓࠋศፔ 24 㛫ᚋࡢ⾑୰Ca ⃰ᗘࡣ㸪ศፔᙜ᪥ẚ㍑ࡋ࡚᭷ពቑຍࡋࡓࠋPTH ࡣ⾑୰ Ca ⃰ ᗘࡀపୗࡋࡓୖ⓶ᑠయࡽศἪࡉࢀ㸪⭈⮚࡛ࡢ 1,25-(OH)2D ࡢྜᡂࢆಁ㐍 ࡍࡿ[33]ࠋஙᚋᮇࡢ㣫ᩱࡀప DCAD ್ࡢሙྜ㸪1,25-(OH)2D ࡀ༑ᣦ⭠ࡽ ࡢ Ca ࡢ྾ࢆಁ㐍ࡋ㸪ప Ca ⾑ࡢ≧ែࡽᅇࡍࡿࡓࡵせࡍࡿ㛫ࡣ㧗 DCAD ್ࡢሙྜẚ㍑ࡋ࡚᪩ࡃ㸪࠾࠾ࡴࡡ 15㹼24 㛫ゝࢃࢀ࡚࠸ࡿ[33]ࠋᑐ ↷⩌࡛ࡣศፔᙜ᪥ 1,25-(OH)2D ࡼࡗ࡚༑ᣦ⭠ࡽࡢ Ca ࡢ྾ࡀಁ㐍ࡉ ࢀࡓࡶࡢ᥎ᐹࡉࢀࡓࠋ
ᑐ↷⩌DFA ⩌ࡢ⾑୰ OC㸪ucOC ࠾ࡼࡧ NTx ⃰ᗘ㸪OC/NTx ẚ㸪ucOC/OC ẚ㸪ࡉࡽᒀ୰Ca/Cre ẚࡣ⩌㛫࠾ࡼࡧ⩌ෆᕪࡣぢࡽࢀ࡞ࡗࡓࠋࡋࡓࡀࡗ࡚㸪 ୧⩌࠾࠸࡚㸪ᾘ⟶྾ࡉࢀࡓ Ca ࡢከࡃࡣ⫾Ꮚ⛣⾜ࡋࡓࡇࡀ♧၀ࡉࢀ ࡓࠋ ᮏ❶࠾࠸࡚㸪DFA ⩌ࡢศፔணᐃ 120 ᪥๓ࡢ⾑୰ T-cho ⃰ᗘࡣ㸪ᑐ↷⩌ẚ ㍑ࡋ࡚᭷ព࡞㧗್ࢆ♧ࡋࡓࠋ⾑୰ T-Cho ⃰ᗘࡣ⥲ྜⓗ࡞࢚ࢿࣝࢠ࣮ࡢᦤྲྀ≧ἣ ࢆᫎࡋ[16㸪29]㸪Ἢங᪥ᩘ㸪Ἢங㔞࠾ࡼࡧ᥇㣗㔞ᙳ㡪ࢆཷࡅࡸࡍ࠸[16㸪64]ࠋ ᑐ↷⩌࠾ࡼࡧDFA ⩌࠾ࡅࡿศፔணᐃ 120 ᪥๓ࡢἪங᪥ᩘࡣࡑࢀࡒࢀ 308.75 s7.03 ᪥࠾ࡼࡧ 278.13s6.15 ᪥㸪1 ᪥ᙜࡓࡾࡢἪங㔞ࡣࡑࢀࡒࢀ 40.3 ± 0.5 kg ࠾ࡼࡧ41.0 ± 0.5 kg ࡛࠶ࡾ㸪ᕪࡣ࡞ࡗࡓࠋ᥇㣗㔞ࢆᫎࡍࡿ࣮࣓ࣝࣥࣇࣝ ࢫࢥ㸦RFS㸧[4]࠾࠸࡚㸪ศፔணᐃ 120 ᪥๓ࡢᑐ↷⩌ DFA ⩌ࡢࢫࢥࡣࡑ ࢀࡒࢀ 3.50s0.06 ࠾ࡼࡧ 3.63s0.06 ࡛ᕪࡣ࡞ࡗࡓࠋᖖ࡞Ἢங∵ࡢ⾑୰
T-33 cho ⃰ᗘࡢᇶ‽⠊ᅖࡣ 130㹼300 mg/dL[24]࡛࠶ࡾ㸪୧⩌ࡢศፔணᐃ 120 ᪥๓ࡢ ⾑୰T-cho ⃰ᗘࡣࡑࡢ⠊ᅖෆ࡛࠶ࡗࡓࠋࡋࡓࡀࡗ࡚㸪ᮏ❶ࡢヨ㦂࠾࠸࡚㸪౪ヨ ∵ࡢ⩌ศࡅࡁ࡞ၥ㢟ࡣ࡞ࡗࡓ⪃࠼ࡽࢀࡓࠋ ⤖ㄽࡋ࡚㸪Ἢஙᚋᮇࡽศፔࡲ࡛㛗ᮇ㛫ࡢ DFAϪ⤥㣵ஙᚋᮇ㣫ᩱࡢ DCAD ್ㄪᩚࡢే⏝ࢆ⾜ࡗࡓᮏ❶ࡢヨ㦂⤖ᯝࡽ㸪ศፔணᐃ 120 ᪥๓ࡽ 90 ᪥๓ࡢἪஙᚋᮇࡢங∵࡛ࡣ㣫ᩱࡽࡢCa ྾ࡀቑຍࡋ㸪㦵྾ࡀᢚไࡉࢀ㸪㦵 ᙧᡂࡀඃ࡞≧ែ࡞ࡿࡇࡀ♧၀ࡉࢀࡓࠋศፔணᐃ90 ᪥๓௨㝆࡛ࡣ㸪ᾘ⟶ ྾ࡉࢀࡓCa ࡢከࡃࡀ⫾Ꮚ⛣⾜ࡍࡿ⪃࠼ࡽࢀࡓࠋࡉࡽ DFAIII ࡢ⤥㣵 ࡼࡗ࡚㸪ศፔᙜ᪥⏕యෆ࡛⏝ྍ⬟࡞Ca 㔞ࡀቑຍࡋ㸪⾑୰ Ca ⃰ᗘࡢపୗࡀ ⦆ࡉࢀࡿࡇࡀ᥎ᐹࡉࢀࡓࠋ
55. ᑠᣓ
ங∵ᑐࡋ࡚Ἢஙᚋᮇࡽศፔࡲ࡛㛗ᮇࡢ DFAϪ⤥㣵ஙᚋᮇ㣫ᩱࡢ DCAD ್ㄪᩚࢆ⾜࠸㸪㦵௦ㅰ࠾ࡼࡧ Ca ௦ㅰ࠼ࡿᙳ㡪ࡘ࠸᳨࡚ドࡋࡓࠋ ศፔணᐃ120 ᪥๓㹼90 ᪥๓ࡢ DFA ⩌࠾࠸࡚⾑୰ OC/NTx ẚࡣ᭷ពቑຍࡋ ࡓࡓࡵ㸪DFA III ᦤྲྀࡼࡿ Ca ࡢ྾ಁ㐍㦵྾ࡢᢚไࡼࡾ㸪㦵ᙧᡂඃ ࡢ≧ែ࡞ࡗࡓ⪃࠼ࡽࢀࡓࠋศፔணᐃ90 ᪥๓௨㝆㸪⾑୰ࡢ㦵௦ㅰ್࣐࣮࣮࢝ ኚࡣ࡞࠸ࡀ㸪ᒀ୰Ca/Cre ẚࡣᑐ↷⩌࡛ࡢࡳ᭷ពቑຍࡋࡓࠋࡇࡢࡇࡣ Ca ࡢஙࡢ⛣⾜ࡀῶᑡࡋ⫾Ꮚࡢ⛣⾜㔞ࡀቑຍࡍࡿࡇࡢᮇ࠾࠸࡚㸪ᒀࡢCa ฟࡀቑຍࡋࡓࡇࡀ᥎ᐹࡉࢀࡓࠋ୍᪉㸪DFA ⩌࡛ᒀ୰ Ca/Cre ẚࡢኚࡀ࡞ ࡗࡓࡇࡣ㸪ᾘ⟶྾ࡉࢀࡓCa ࡢከࡃࡀ⫾Ꮚ⛣⾜ࡋࡓࡓࡵ㸪㦵ࡢ⛣⾜ 㔞ࡀῶᑡࡋࡓ⪃࠼ࡽࢀࡓࠋศፔᙜ᪥ࡢ⾑୰Ca ⃰ᗘࡣ୧⩌ࡶ᭷ពపୗࡋ ࡓࡀ㸪DFA ⩌ࡢ⾑୰ Ca ⃰ᗘࡣᑐ↷⩌ẚ㍑ࡋ࡚᭷ព࡞㧗್ࢆ♧ࡋࡓࠋࡍ࡞ࢃ ࡕ㸪DFA ⩌࡛ࡣἪஙᚋᮇࡽࡢ DFAIII ⤥㣵ஙᚋᮇ㣫ᩱࡢ DCAD ್ㄪᩚ ࡼࡗ࡚㸪ศፔᙜ᪥⏕యෆ࡛⏝ྍ⬟࡞Ca 㔞ࡀቑຍࡋ㸪⾑୰ Ca ⃰ᗘࡢపୗࡀ34 ⦆ࡉࢀࡓࡇࡀ♧၀ࡉࢀࡓࠋ
35
66. ᅗ⾲
7DEOHʁൽغ705ɼףغ705ɼףغഓ͕Γ;οϠεʖףԿָૌ ߴ ൽ705 ף705 ףغഓ οϠεʖף 1') $') &3 (( $VK &D 3 0J . 1D &O 6 '&$'ʤP(TJ'0ʥ ʥ'&$'Ґͺસͱʤ'0ʥ45
46 ங∵࡛ࡣ⏘ḟࢆ㔜ࡡࡿࡈங㔞ࡣቑຍࡍࡿࡀ㸪㦵ᐦᗘࡣపୗࡍࡿࡇࡀሗ ࿌ࡉࢀ࡚࠸ࡿࠋࡇࢀࡣ㸪ங㔞ࡀቑຍࡍࡿἪஙึᮇ࡛ࡣ⏕యෆࡢCa 㔞ࡀῶᑡࡍ ࡿࡀ㸪ᾘ⟶ࡽ྾ࡉࢀࡿCa 㔞࡛ࡣ⿵ࡀ㛫ྜࢃࡎ㸪㦵྾ࡼࡗ࡚⿵ ሸࡍࡿࡇ㉳ᅉࡍࡿࠋ୍᪉㸪Ἢஙᚋᮇࡶࡋࡃࡣஙᮇ࡛ࡣங㔞ࡀῶᑡࡲࡓࡣ Ṇࡍࡿࡇࡽ㸪⏕యෆࡢCa 㔞ࡀቑຍࡋ࡚㦵ᙧᡂࡀάᛶࡍࡿࠋࡋࡓࡀࡗ ࡚㸪ங∵ࡢ㦵ᐦᗘࡢపୗࢆᢚไࡍࡿࡓࡵࡣ㸪Ἢஙᚋᮇࡽஙᮇࡅ࡚ Ca ࢆ౪⤥ࡍࡿࡇࡀ୍ࡘࡢ᪉ἲ⪃࠼ࡽࢀࡿࠋࡋࡋ㸪Ἢஙᚋᮇࡽศፔࡲ ࡛ࡢங∵㛗ᮇ㛫ࢃࡓࡾCa ࢆ㣫ᩱῧຍࡋ㸪㦵ᐦᗘ㸪㦵௦ㅰ࡞ࡽࡧ Ca ௦ ㅰࡢ㠃ࡽ᳨ドࡋࡓᏛ⾡ሗ࿌ࡣࢇぢᙜࡓࡽ࡞࠸ࠋ DFAϪࡣࣇࣛࢡࢺ࣮ࢫ 2 ศᏊࡀ⤖ྜࡋࡓ㞴ᾘᛶࡢ࢜ࣜࢦ⢾࡛࠶ࡾᑠ⭠ୖ⓶ ⣽⬊㛫㝽ࡢTJ స⏝ࡋ㸪Ca ࡢཷື྾ࢆಁ㐍ࡍࡿࡇ࡛ Ca ࡢ྾⋡ࢆቑຍ ࡉࡏࡿࠋศፔ๓ᚋࡢங∵ᑐࡍࡿ DFAϪ⤥㣵࡛ࡣ㸪ᾘ⟶ࡽࡢཷື㍺㏦ࢆక ࠺ Ca ྾ࡀಁ㐍ࡉࢀ㸪࣐࢘ࢫ࡛ࡣ DFAϪ⤥Ⲵ㔜ࢆ⤌ࡳྜࢃࡏࡿࡇ࡛㦵 ᐦᗘࡀቑຍࡍࡿࡇࡀ▱ࡽࢀ࡚࠸ࡿࠋ ᮏ◊✲࡛ࡣ㸪Ἢஙᚋᮇ࡞ࡽࡧஙᮇDFAϪࢆ㣫ᩱῧຍࡋࡓሙྜࡢ㦵࣑ࢿ ࣛࣝ㦵௦ㅰືែࢆ᫂ࡽࡍࡿࡓࡵ㸪᭱ึἪஙᚋᮇ∵ᑐࡍࡿDFAϪ⤥ 㣵ࡀ㦵ᐦᗘ㦵௦ㅰ࠼ࡿᙳ㡪ࡘ࠸᳨࡚ウࡋ㸪ḟἪஙᚋᮇࡽศፔ┤ᚋ ࡅ࡚㛗ᮇ㛫ࢃࡓࡿங∵ࡢDFAϪ⤥㣵ࡀ㦵௦ㅰ࠾ࡼࡧ Ca ௦ㅰ࠼ࡿ ᙳ㡪ࡘ࠸᳨࡚ウࡋࡓࠋᚓࡽࢀࡓ▱ぢࡣ௨ୗࡢ㏻ࡾ࡛࠶ࡿࠋ 㸯㸬Ἢஙᚋᮇࡢங∵ᑐࡍࡿDFAϪ⤥㣵ࡀ㦵ᐦᗘ࠼ࡿᙳ㡪 Ἢஙᚋᮇࡢங∵ᑐࡋ࡚ 28 ᪥㛫⥅⥆ⓗ DFAϪࢆ⤥㣵ࡋ㸪㦵ᐦᗘ࡞ࡽࡧ 㦵௦ㅰཬࡰࡍᙳ㡪ࡘ࠸᳨࡚ドࡋࡓࠋDFA ⤥㣵ࡼࡗ࡚㸪28 ᪥┠➨ 4 ᑿ᳝ ࡞ࡽࡧ୰ᡭ㦵ࡢ㦵ᐦᗘࡢቑຍ⾑୰ ucOC/OC ẚࡢῶᑡࡀㄆࡵࡽࢀࡓࡇ ࡽ㸪㦵ࡢ▼⅊ࡢಁ㐍ࡼࡿ㦵࣑ࢿࣛࣝቑຍࡀ♧၀ࡉࢀࡓࠋࡲࡓ㸪DFAϪ⤥㣵
47 ࡼࡗ࡚ங୰Ca ⃰ᗘࡀ 28 ᪥┠ቑຍࡋࡓࡇࡽ㸪ᾘ⟶྾ࡉࢀࡓ Ca ࡢከ ࡃࡀங⭢ฟࡉࢀࡓࡇࡀ♧၀ࡉࢀࡓࠋ 㸰㸬Ἢஙᚋᮇࡽศፔᚋࡲ࡛ࡢங∵ᑐࡍࡿ㛗ᮇࡢ DFAϪ⤥㣵ࡀ㦵࠾ࡼࡧ Ca ௦ㅰ࠼ࡿᙳ㡪 ங∵ᑐࡋ࡚Ἢஙᚋᮇࡽศፔࡲ࡛㛗ᮇࡢ DFAϪ⤥㣵ஙᚋᮇ㣫ᩱࡢ DCAD ್ㄪᩚࢆ⾜࠸㸪㦵௦ㅰ࠾ࡼࡧ Ca ௦ㅰ࠼ࡿᙳ㡪ࡘ࠸᳨࡚ドࡋࡓࠋ DFAIII ࡢ⤥㣵ࡼࡗ࡚ศፔணᐃ 120 ᪥๓㹼90 ᪥๓ࡢ⾑୰ OC/NTx ẚࡣ᭷ព ቑຍࡋࡓࡓࡵ㸪Ca ࡢᾘ⟶྾ࡢಁ㐍㦵྾ࡢᢚไࡼࡾ㸪㦵ᙧᡂඃࡢ≧ ែ࡞ࡗࡓ⪃࠼ࡽࢀࡓࠋศፔணᐃ 90 ᪥๓௨㝆㸪DFAIII ⤥㣵࡛ࡣ⾑୰㦵௦ㅰ ್࣐࣮࣮࢝ᒀ୰Ca/Cre ẚኚືࡣ࡞ࡗࡓࠋࡋࡓࡀࡗ࡚㸪Ca ࡢஙࡢ⛣⾜ ࡀῶᑡࡋ⫾Ꮚࡢ⛣⾜㔞ࡀቑຍࡍࡿࡇࡢᮇ࠾࠸࡚㸪DFA ⤥㣵࡛྾ಁ㐍ࡉ ࢀࡓCa ࡢከࡃࡀ⫾Ꮚ⛣⾜ࡋࡓࡇࡀ♧၀ࡉࢀࡓࠋศፔᙜ᪥ࡢ⾑୰ Ca ⃰ᗘࡣ ࡍ࡚ࡢ౪ヨ∵࡛పୗࡋࡓࡀ㸪DFAIII ⤥㣵ࡋࡓங∵ࡣࡑࡢపୗࡀ㍍ᗘ࡛࠶ࡗࡓࠋ ࡇࢀࡣἪஙᚋᮇࡽࡢDFAIII ⤥㣵ஙᚋᮇ㣫ᩱࡢ DCAD ್ㄪᩚࡼࡾ⏝ ྍ⬟࡞Ca 㔞ࡀቑຍࡋࡓࡇ࡛㸪ศፔᙜ᪥ࡢ⾑୰ Ca ⃰ᗘࡢపୗࡀ⦆ࡉࢀࡓࡶ ࡢ⪃࠼ࡽࢀࡓࠋ ௨ୖࡼࡾ㸪ங∵ࡢἪஙᚋᮇࡽศፔ┤ᚋࡅ࡚DFAϪ㣫ᩱῧຍࡣἪஙࡸዷ ፎࡢࢫࢸ࣮ࢪࡼࡾ㦵ࡸஙỒ㸪⫾ᏊࡢCa ౪⤥ࢆಁࡋ㸪ࡉࡽஙᚋᮇ㣫ᩱ ࡢDCAD ್ㄪᩚࡢే⏝ࡼࡗ࡚ศፔᙜ᪥ࡢ⾑୰ Ca ⃰ᗘࡢపୗࢆ⦆ࡍࡿࡇ ࡀ♧၀ࡉࢀࡓࠋࡃ㸪Ἢஙᚋᮇ࠾ࡅࡿDFAIII ࡢ⤥㣵ࡣ㦵ᐦᗘࡢቑຍࢆ ຓ㛗ࡋ㸪⏘ḟࡢቑຍక࠺㦵ᐦᗘపୗࢆண㜵ࡍࡿྍ⬟ᛶࡀ࠶ࡿࡇࡽ㸪ங∵ ࡢ㛗㐃⏘㈉⊩ࡍࡿ᪂ࡋ࠸㣫㣴ᢏ⾡ࡋ࡚ᮇᚅࡉࢀࡿࠋ
48
ःࣛ
ᮏ◊✲ࡣ➹⪅ࡀᒱ㜧ᏛᏛ㝔⋇་Ꮫ◊✲⛉༤ኈㄢ⛬࠾࠸࡚⾜ࡗࡓᐇ㦂ࢆ ࡲࡵࡓࡶࡢ࡛࠶ࡾ㸪ᐇ㦂ࡣᖏᗈᕷෆࡢ୍⯡㓗㎰ᐙ࡚ᐇࡉࡏ࡚㡬ࡁࡲࡋ ࡓࠋᣦᑟᩍဨ࡛࠶ࡿඖᖏᗈ␆⏘Ꮫᩍᤵ㸦⌧㜰ᗓ❧Ꮫᩍᤵ㸧࣭ᒣᓊ๎ኵඛ ⏕㸪➨㸯ᣦᑟᩍဨ࡛࠶ࡿᖏᗈ␆⏘Ꮫᩍᤵ࣭ᯇᮏ㧗ኴ㑻ඛ⏕࡞ࡽࡧඖᖏᗈ ␆⏘Ꮫᐈဨ◊✲ဨ࣭⩚❧⸅༤ኈࡣ㸪⤊ጞ㸪ບࡲࡋᡭཌ࠸ࡈᣦᑟ࣭ࡈຓࢆ ㈷ࡾࡲࡋࡓࡇ῝ࡃᚚ♩⏦ࡋୖࡆࡲࡍࠋࡲࡓ㸪ᖏᗈ␆⏘Ꮫᩍᤵ࣭༡ಖὈ㞝ඛ ⏕㸪ᒾᡭᏛᩍᤵ࣭ᮌᓮᬒ୍㑻ඛ⏕㸪ᮾி㎰ᕤᏛᩍᤵ࣭⏣୰▱ᕫඛ⏕㸪ᒱ㜧 Ꮫᩍᤵ࣭ሙᜨඛ⏕ࡣ㸪ᮏᏛㄽᩥࡢᡂࡢࡓࡵኚ᭷ព⩏࡞ࡈᣦᑟࡈ ຓゝࢆ㈷ࡾ㸪ཌࡃᚚ♩⏦ࡋୖࡆࡿḟ➨࡛ࡍࠋ᭱ᚋ㸪ᮏ◊✲ࡢᶵࢆ࠼࡚࠸ࡓ ࡔࡁ㸪ࡈᣦᑟࡈ㠴᧡ࢆ㈷ࡾࡲࡋࡓ᪥ᮏ⏓⳯〇⢾ᰴᘧ♫⥲ྜ◊✲ᡤ࡞ࡽࡧ㣫 ᩱᴗ㒊ࡢⓙᵝᚰࡼࡾ῝ㅰ⏦ࡋୖࡆࡲࡍࠋ㻌49
ᘬ
ᘬ⏝ᩥ⊩
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