ęඈඋ1࣏ۘऺ ৰ 21 Ż ৰ 33 ƛ 20171128 ϦČ Chinese Journal of Tissue Engineering Research November 28, 2017 Vol.21, No.33 www.CRTER.org

ऺƣጛۘ 2Ƨசɳ҉۔ปʸ′⍤༘Ȍ࿆཮¾ඊྡྷࢿΉ͏ћ̓
ăএ) ϴ ዐ(ǧSďS˂ˡŋʒ½ˍãKǧSď 300350) .Ƨசɳ҉[J].ęඈඋ1࣏ۘऺ 2017 21(33):5325-5331 2 ۔šϬƨăএ) ϴዐ. ปʸ′⍤༘Ȍ࿆཮¾ඊྡྷࢿΉ͏ћ̓ DOI:10.3969/j.issn.2095-4344.2017.33.013 ORCID: 0000-0001-9343-6732(ăএ))

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ྴˏඊྡྷηϔₓʺ¤(P < 0.05) ྴှඈඋ CXCL13CXCL2 ǎ͢ǛĿ CXCR2 ᖏՁᜬẂŋʌ(P < 0.05) ྴ ˏඈඋƮɍ௎] ±ᢅɅₓྴˏඊྡྷþ ^µƧඈɨṇ ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈ3ǒɀඈाွᜄச

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͟⏲᪑ ҋᱏĚüƄ̺۔ඊྡྷ࿆཮¾ඊྡྷปʸ′⍤ࢿΉசɳ҉̓¾

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Therapeutic effect of rosiglitazone combined with adipose-derived stem cell transplantation in rats with type 2 diabetes mellitus Kang Li-li, Attending Kang Li-li, Tian Meng (Department of Internal Medicine, Tianjin Jinnan District Xianshuigu Hospital, Tianjin 300350, physician, Department of China) Internal Medicine, Tianjin Jinnan District Xianshuigu Hospital, Tianjin 300350, Abstract China BACKGROUND: Studies have shown that high glucose environment has a significant inhibitory effect on the

ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH 5 3 2 5

Ƨசɳ҉ www.CRTER.org 2 ۔ăএ) ਍. ปʸ′⍤༘Ȍ࿆཮¾ඊྡྷࢿΉ͏ћ̓ survival of adipose-derived stem cells, which significantly affects the therapeutic efficacy of adipose-derived stem cells on type 2 diabetes mellitus. OBJECTIVE: To investigate the therapeutic effect of rosiglitazone combined with adipose-derived stem cell transplantation in rats with type 2 diabetes mellitus. METHODS: A total of 108 male Sprague-Dawley rats were chosen, 20 of which were randomly taken as normal controls and the rest 88 rats were used to make type 2 diabetes mellitus models through intraperitoneal injection of low-dose streptozotocin combined with high-sugar/high-fat diet. At 20 days after modeling, the model rats were randomized into model, rosiglitazone, cell transplantation and combined groups, followed by administration of normal saline (by gavage and via tail vein), rosiglitazone (by gavage), adipose-derived stem cells (via tail vein), and rosiglitazone (by gavage)+adipose-derived stem cells (via tail vein), once a day, for consecutive 7 days. Three weeks after treatment, fasting blood glucose level, insulin level, C-peptide level, body mass changes were detected; distribution and survival of adipose-derived stem cells were observed; the changes of pancreas histomorphology was observed, the apoptosis in islet cells was detected, and the CXCL1, CXCL2 and CXCR2 protein expression levels in the pancreas tissue were determined. RESULTS AND CONCLUSION: Compared with the normal control group, the fasting blood glucose level was increased (P < 0.05), while the insulin level, C-peptide level and body mass were significantly decreased in the model group (P < 0.05); the number of apoptotic islet cells was increased (P < 0.05); the expression levels of CXCL1, CXCL2 and CXCR2 in the pancreas tissue were elevated (P < 0.05); and the pancreas tissue morphologies were in disorder, with few islet cell masses. Compared with the model group, the fasting blood glucose level was decreased (P < 0.05), while the insulin level, C-peptide level and body mass were significantly increased in the rosiglitazone, cell transplantation and combined groups (P < 0.05); the number of apoptotic islet cells was decreased (P < 0.05); the expression levels of CXCL1, CXCL2 and CXCR2 in the pancreas tissue were declined (P < 0.05); and the pancreas tissue morphologies were improved to different extents, and the combined group showed the best improvement. There were many transplanted adipose-derived stem cells in the cell transplantation and combined groups, especially in the latter one. Overall findings indicate that rosiglitazone combined with adipose-derived stem cell transplantation is an effective treatment for type 2 diabetes mellitus in rats, which is better to inhibit inflammations. Subject headings: Stem Cells; Diabetes Mellitus; Cell Transplantation; Tissue Engineering

Cite this article: Kang LL, Tian M. Therapeutic effect of rosiglitazone combined with adipose-derived stem cell transplantation in rats with type 2 diabetes mellitus. Zhongguo Zuzhi Gongcheng Yanjiu. 2017;21(33):5325-5331.

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5326 P.O. Box 10002, Shenyang 110180 www.CRTER.org

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60 ?ʞÕˈ ੵ 30 sͱẟᜐȷợ̩ᆓ4ᙑĚ7ȒȺ࿆཮ ྡྷʃᩴɋ[22-24]4 ȏ̠̓⁍ٯඊྡྷẉ҂Ḱ͑EP੥¤͑DMEMȕͧȖ ₑ̩ɃȏȽ· ᆓƤஂ.ö൦ɏᄶᢆȓྴှඈඋƮɍǜĚ¾ ϔ10%϶ Ėǎྴှඈඋ ÂǚϦྴှඈඋ ϬĿࢳ۔ O ╓ȒࡿȏŏZ±^4Ⱥ̩ᆓȒՈඊྡྷϬ ඊྡྷū͢ţĄ DMEMǀ͔ȕͧȖ᫇Ϙ&1×109 L
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ö൦ɏ Ϭ500 µL PBSₑ˸ඊྡྷ ϕśඊྡྷÖ̼ϟỤᜄඊྡྷᜬ☦ʃᩴ ᄶ4ɏᄶȒՈ ċඓ൳E⁋࿵ˈ ͹ඓx϶ᆳū ċồŠ4 ċƠZ¤ţ̓ʍྺ ֚Z֚ɿċȵĖ4Ǒʍ ĭՈᜬẂ4 Ⱥ>ồŠՈ ှඈඋՈƮɍǜྴ۔ℸǎǀtȒ ࡿȏƿZ±ΫP Ⱥ࿆཮¾ඊྡྷϧò᫇ ྺ¾©Ȓ ራ̵ºǺ␠[ᢆȓȈඈ̓ Ϙ&8×108 L
1 ╓Ȓȕඊྡྷ˸^¤͑5 µL CM-DiLʃᩴ Ě4 ǚྴှඈ۔30 minȒ ࡿȏŏZ TUNEL̼ͩϟྴˏඊྡྷη̑Ρ̠ȏ̓ ඊྡྷ╓ȒาzȕͧੵʃᩴƩĚ25 ċ„ᢈ࿵ᗥ ᗥڷ ċ͝ᩥϔ5 ှඈඋྴ۔PBSₑ˸ ₑ̩ʃᩴ2Ƶ ºǺ␠[ᢆȓඊྡྷʃᩴՈ̑ උ ɣǮ̓ ± Ρ4␠[dzᢅ࿆཮¾ඊྡྷʃᩴºɴϦѐᄷՈì൦ᄶhPᄶ ႷˈƠ¤1Ơ̩Ȍ4Ě^(ᖏՁ›K^྇ᖏՁ›) 25 ?Ʃ ţĄ ̣Ϭ4 Ě20 min ΫPȒƠ¤TUNELʃᩴǑà£Ȍ^50 µL ń ƶ ī֖37 ?Ʃྲྀ1 h Ơ¤POD2ḰĚ^50 µL ī֖ 37╓۔ඈ¾8 º108ǮSD̓ சɳ҉Ụµǎ 1.4.2 ö൦̩ Ảන₋“7ɬՈʌ ?Ʃྲྀ30 min PBSΞΫ3Ƶ DABºᄶᆓƤஂ۔ọǚ20Ǯň&Ƿ„ȭ+ඈ Ņ88ǮSD̓ ᄶඊྡྷʴՈඊྡྷ&ηඊྡྷ ᩥϔٸசʌ࿆Ģ“(ʌ࿆ʌசĦȯ10%Ꮫச310%Ǯ͍ǎ5%ྊĖ ɏ ºǺ␠[dzᢅ͑ ⁋)7Ȓ Ảන3 dႮွဘͼȸɃFₓ⏂࿶◍௤(45 mg/kg) ηඊྡྷϔₓÂᩥਜ਼ඊྡྷηɋ[25-26]4 ņএ2Ƨசɳ҉µƧ4ỤµȒ20 d ỞẋᜄசÖ̼ϟỤµ̓ Western blot̼ͩϟྴှඈඋCXCƧᱏĚüƄ‑Ŀ ۔Ոɲ☝࿍ᜄ^Ոᜄசˈ¿ Ⱥ̼ϟ඗ȘϧඌÑȭ+Ոᜄ CXCL13CXCL2ǎ͢ǛĿCXCR2ᖏՁᜬẂˈ¿ǚ̓۔ சȨ(16.7 mmol/L)ň&ņµt£Ոʃβ4 ྴှඈඋ ʵǒBCA᪙F֖ȴǚÂϟǎྴှඈඋᖏՁϧò &4ඈ ɣඈ19 ੄໐ᣄ7Ⱥඊྡྷឆᢧ7ÂȺ7ࣄ₎ႷּȐՈᖏՁϧò ƶ╓۔Ⱥżඌņµt£Ո76ǮSD̓ ǮµƧඈ˸྇ඝtϣˊ֔ˈ1 mL ɲ☝࿍ͼȸ1 mLϣˊ 100 ?2͌5 min ūᖏՁǜɳ4ɣඈǚᖏՁ40 µg 10% ปʸ′⍤ඈ˸྇ඝt4 mg/(kg࠽d)ปʸ′⍤(1 mL SDS-PAGEωྺϹ·(70 V 30 min100 V 90 min)Ḱˈ֔ ϣˊ֔ˈŢᢧ) ɲ☝࿍ͼȸ1 mLϣˊ֔ˈ࿆཮¾ඊྡྷඈ ၠ(200 mA 3 h)ႷPVDFၠ5%࿵࿆ğΒǘÕȵ⒱2 h(z ඝt1 mLϣˊ֔ˈ ɲ☝࿍ͼȸ1 mL࿆཮¾ඊྡྷ˸^ 4 ?ẋ̸)Pû1a500 ǘÕƩྲྀ2 h (z4 ?ẋ̸)TPBS྇˸ (ඊྡྷϧò1×107 L
1) ǒɀඈ˸྇ඝt4 mg/(kg࠽d)ปʸ ΫP3Ƶ PBSΫP1Ƶ7ȒẟᜐᖏՁ̹ѯŴẽՈǑà Ȍ ϟǎȈඈྴှඈඋ ⍤(1 mLϣˊ֔ˈŢᢧ) ɲ☝࿍ͼȸ1 mL࿆཮¾ඊྡྷ˸ ı+ᩴơ7ȒẟᜐḳâՈĚʻ′ ^)¿ˈඊྡྷϧò1×107 L
1)4ȈඈẢන¾87 d 1Ƶ/d4 CXCL13CXCL2ǎ͢ǛĿCXCR2ᖏՁᯬּȭᜬẂ)^ 1.5 ƶϙʬ+ŷ/ ͏ћȒ3ɬ ẟᜐÑ[̼ϟ4 β-actinՈ̜òࢳ ɨȨ) ň&CXCL13CXCL2ǎ͢ǛĿ ाွᜄச3ྴˏ௤3C
ཱྀǎĿᯬₓǜĚ̼ϟ CXCR2ᖏՁᜬẂՈₓ4۔̓ Ȍα͸ǫʭ ¤ƅϔǒᰈՈඈⒸɨṇ₋Ϭřü௤ 1.6 ۔ाွᜄசʐĿᯬₓǜĚ(ń̼ϟ7Q◄ᡅȭ̓۔Ȉඈ̓ _ Ȍ ǒɀ඗ȘÑx±sᜬ߾ Ո 5:(One-way ANOVA)࣏Û۔ẟᜐ12 hՈाွ̠ˊ)4ाွᜄசỞẋᜄசÖ̼ϟ̓ ဘ☝ ÂᢈǎP < 0.05&:Ŏƅºጛɳ͛54]۔z̓ ۔ɲ☝࿍ᜄՈᜄசȯₓ ╓Ȓ̠ȏ̓ ཱྀ ाွྴˏ௤ʐC۔࿍ġᜄ ₋ϬELISA᪙F֖ϟǎ̓ ˈ¿4 2

඗Ș

Results ራ̵ºǺ␠ᢆȓCM-Dil⓷ɳඊྡྷ OǎƌϏ₋▊̓ 2.1 ūǓȼˍFĝ́Ƨʬ+ ǒɀọǚĿ̲ȕͧႷP3Ï Ոϣ⑃v֟Ո࿆཮¾ඊྡྷ ΞĚ1¤߾ ৰ3Ï࿆཮¾ඊ ċÂẟᜐ4’ 6 ှඈඋΜΧྴ۔ှඈඋ :ň̓ྴ۔ x࿖Ȗ 2ᆳȖȶ˞ɏᄶ4¾©Ȓ ºǺ␠[ᢆȓr ╓ ྡྷȕͧYͅȒ ඊྡྷ¿⎾᱉ẋκá80%ÑZ ඊྡྷɌ ƶọǚɣŬΣΧ ċՈ3ᢊₒhȭ7ẟᜐı+ᩴơȳ ▊ጁʳϣ⑃ ʴ­Šº ඗Ȁ±ì ƮɍĨt൨මʳඊ ᪂ɣŬ+ċՈʇšò&1 ɣŬ+ċọǚP̵šòͥ ྡྷ ඊྡྷᜬ☦̵Ž Oṇ&ţĄ dzᢅŠºǕMźՈ -ϬACDsee5.0ḳâܲǎ͢ŬʃȨ4ńĚʻ╓ƶọǚ8 ඊྡྷ̷╊ ƾඊྡྷȖƨ4͍Čৰ3ÏՈ࿆཮¾ඊྡྷºɴ ᢊₒ ᩥϔɣᢊₒ7CM-DilʃᩴՈ⓷ɳඊྡྷϔǎ ϦѐᄷՈì൦ᄶhPᄶţĄ4࿆཮¾ඊྡྷՈᜬ☦ʃᩴĭ ᢊₒ࿆཮¾ඊྡྷʇϔ Âᩥਜ਼ྴှඈඋՈ࿆཮¾ඊ ᜬẂ ᢅĚ24

ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH 5327

Ƨசɳ҉ www.CRTER.org 2 ۔ăএ) ਍. ปʸ′⍤༘Ȍ࿆཮¾ඊྡྷࢿΉ͏ћ̓

ाွᜄச3ྴˏ௤3C
ཱྀǎĿᯬₓՈǜĚ۔A B ᜬ 1 ͏ћ 3 ɬȈඈ̓ _ (x±s) Table 1 Changes of fasting blood glucose level, insulin level,

C-peptide level, and body mass in rats of each group at 3 weeks after treatment

ඈ/ ाွᜄச ྴˏ௤(mmol/L) C
ཱྀ(µg/L) ĿᯬₓǜĚ(g) (mmol/L)

Ě 1 ࿆཮¾ඊྡྷՈƮɍᢆȓ(×200) Ƿ„ȭ+ඈ 5.3±1.2 3.2±0.8 1.2±0.2 32.4±8.1 a a a a F igure 1 Morphology of adipose-derived stem cells (×200) µƧඈ 21.3±3.4 0.5±0.1 0.3±0.1 11.5±2.9 ĚͼĚ A &ৰ 3 Ï࿆཮¾ඊྡྷ ඊྡྷɌ▊ጁʳϣ⑃ ʴ­Šº ปʸ′⍤ඈ 11.8±1.5b 1.7±0.7b 0.8±0.2b 20.4±5.5b b b b b ඗Ȁ±ì ƮɍĨt൨මʳඊྡྷ ඊྡྷᜬ☦̵Ž Oṇ&ţĄ dz ࿆཮¾ඊྡྷඈ 12.2±2.2 2.2±0.7 0.8±0.3 21.3±5.8 bc bc bc bc ᢅ ŠºǕMźՈඊྡྷ̷╊B & CM-DiL ʃᩴʃᩴՈ࿆཮¾ඊྡྷ º ǒɀඈ 7.6±1.4 2.7±0.8 1.0±0.2 27.6±7.4 ɴ ϦѐᄷՈì൦ᄶ4 ᜬ ͼ^Ƿ„ȭ+ඈɨṇ aP < 0.05^µƧඈɨṇ bP < 0.05^࿆཮¾ඊ c ྡྷඈ3ปʸ′⍤ඈɨṇ P < 0.054

Ě 2 ৰ 3 Ï࿆཮¾ඊྡྷՈᜬ☦ʃᩴĭᜬẂ Figure 2 Cell surface marker expression of passage 3 adipose-derived stem cells

A B C D E

Ě 3 ͏ћ 3 ɬȒȈඈ CM-Dil ⓷ɳඊྡྷ OǎƌϏ̑Ρ(×100) Figure 3 Distribution and survival of CM-Dil positive cells in each group at 3 weeks after treatment (×100) ှඈඋdzᢅṇ̶Ոྴ۔/&Ƿ„ȭ+ඈ3µƧඈ3ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈǎǒɀඈ4±࿆཮¾ඊྡྷඈʐǒɀඈ̓ ĚͼĚ A
E

CM-Dil ʃᩴ࿆཮¾ඊྡྷ XÑǒɀඈϔₓŰ̶4

A B C D E

(ှඈඋƮɍǜĚ(ᆓƤஂ
ö൦ɏᄶ ×200ྴ۔Ě 4 ͏ћ 3 ɬȒȈඈ̓ Figure 4 The morphological changes of rat pancreatic tissue in each group at 3 weeks after treatment (hematoxylin-eosin staining, ×200) Xඊ/&Ƿ„ȭ+ඈ3µƧඈ3ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈǎǒɀඈ4µƧඈྴˏϔֲºጛλɅ ྴˏዒ෭ Ʈɍ]ᢈ ĚͼĚ A
E ǒɀඈ̓ྴˏϔֲᕁṇǷ܄Ƕ௎]ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈྴˏϔₓṇǷ„ȭ+ඈλɅ IJṇµƧඈºጛŋʌ ྴˏඊྡྷǶϘྡྷ „ȭ+ඈɅ IJºጛʌz͢ÂȈඈ ྴˏඊྡྷǶṇ&Ϙ܄ ඊྡྷ7ⒸՈА└ṇ&±ϖ4

2.2 ɪȆîIJòȬͻǂ*ēŵ*C ŤΛǠƉƘ)̼ ^ ^µƧඈɨṇ ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈ3ǒɀඈाွ Ƿ„ȭ+ඈɨṇ µƧඈाွᜄசˈ¿ŋʌ(P < 0.05) ྴˏ ᜄசţɌŠº[┑(P < 0.05) ྴˏ௤3C ཱྀˈ¿ŋʌ(P < ௤3C ཱྀˈ¿┑ĺ(P < 0.05) Ŀᯬₓ[┑Šº(P < 0.05) 0.05) Ŀᯬₓŋʌ(P < 0.05) ͢ÑǒɀඈάȘżŠº(P <

5328 P.O. Box 10002, Shenyang 110180 www.CRTER.org

Ƨசɳ҉ www.CRTER.org 2 ۔ăএ) ਍. ปʸ′⍤༘Ȍ࿆཮¾ඊྡྷࢿΉ͏ћ̓

A B C D E

(ඊྡྷη̑Ρ(TUNEL ηɏᄶ ×100ˏྴ۔Ě 5 ͏ћ 3 ɬȒȈඈ̓ Figure 5 Apoptosis of islet cells in each group at 3 weeks after treatment (TUNEL, ×100) ĚͼĚ A
E /&Ƿ„ȭ+ඈ3µƧඈ3ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈǎǒɀඈ4^Ƿ„ȭ+ඈɨṇ µƧඈඊྡྷηºጛʺ̶^µƧ

ඈɨṇ ปʸ′⍤ඈǎ࿆཮¾ඊྡྷඈඊྡྷηλɅ ǒɀඈλɅżŠº4

Ƿ„ȭ+ඈ µƧඈ ปʸ′⍤ඈ ࿆཮¾ ปʸ Ƿ„ ǒɀඈ ඊྡྷඈ ′⍤ඈ µƧඈ ȭ+ඈ ࿆཮¾ඊྡྷඈ ǒɀඈ

CXCL1 ¿ 0.8

ˈ 0.7

Ẃ 0.6

CXCL2 ᜬ

Ո 0.5 CXCR2 Ձ 0.4 ᖏ 0.3 ü 0.2 β-actin Ȗ ඈ 0.1 Ȉ 0 CXCL1 CXCL2 CXCR2 ¿ˈှඈඋ CXCL13CXCL2 ǎ͢ǛĿ CXCR2 ᖏՁᜬẂྴ۔Ě 6 ͏ћ 3 ɬȒȈඈ̓ Figure 6 CXCL1, CXCL2 and its receptor CXCR2 protein expression levels in rat pancreas tissue at 3 weeks after treatment Ěͼ^Ƿ„ȭ+ඈɨṇ µƧඈ̺ҋᱏĚüƄ CXCL13CXCL2 ǎ͢ǛĿ CXCR2 ᖏՁᜬẂºጛŋʌ(P < 0.05)^µƧඈּɨ ปʸ′⍤ ඈ3࿆཮¾ඊྡྷඈ3ǒɀඈ̺ҋᱏĚüƄ CXCL13CXCL2 ǎ͢ǛĿ CXCR2 ᖏՁᜬẂºጛ┑ĺ(P < 0.05 P < 0.01)ǒɀඈ CXCL13CXCL2

ǎ͢ǛĿ CXCR2 ᖏՁᜬẂĺzปʸ′⍤ඈ3࿆཮¾ඊྡྷඈ(P < 0.05)4

0.05) ᢅᜬ14 2.6 ɪȆˮȆŮCXCL1!CXCL2ΛΓěǠCXCR2ĉ" 2.3 CM-Dilυ͇ˍFǫ_Λáͻ Ƿ„ȭ+ඈ3µƧඈʐ 2êŋͬ ^Ƿ„ȭ+ඈɨṇ µƧඈ̺ҋᱏĚüƄ > ှඈඋÂƦᢆȓ4ƅCM-DilʃᩴՈ࿆ CXCL13CXCL2ǎ͢ǛĿCXCR2ᖏՁᜬẂºጛŋʌ(Pྴ۔ปʸ′ඈ̓ ှ 0.05)^µƧඈּɨ ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈ3ǒྴ۔཮¾ඊྡྷ⓷ɳඊྡྷƌń࿆཮¾ඊྡྷඈʐǒɀඈ̓ ඈඋƌńƅṇ̶ՈCM-Dilʃᩴ࿆཮¾ඊྡྷ .Ñǒɀඈϔ ɀඈ̺ҋᱏĚüƄCXCL13CXCL2ǎ͢ǛĿCXCR2ᖏՁ ₓŰ̶ ᢅĚ34 ᜬẂºጛ┑ĺ(P < 0.05 P < 0.01) ͢ÑǒɀඈCXCL13 2.4 Ųʱj
̛AŒʬ+ˮȆŮ́Ƨ)̼ Ƿ„ȭ+ CXCL2ǎ͢ǛĿCXCR2ᖏՁᜬẂ┑ĺżºጛ ᢅĚ64 ඈྴˏǺòǷ„.ṽො̵Ž ྴˏͱඊྡྷǶϘ܄ ྡྷϚĥ ϔֲºጛλɅ ྴˏዒ 3

ᩬ᩾

Discussionˏྴ۔ƍ ඊྡྷА└±ϖµƧඈ̓ ෭ Ʈɍ]ᢈ.ඊྡྷǶ௎] dzᢅńᾬ ྴˏඊྡྷ7ͱ ẋʻĚĭ›ĿʺȪĭɬϏǛĿ«P࢑,Ոɬ௤ǛĿ ƌƅ࿆ᯬ̝ࢳ ᜄ੥ḿòʺϣปʸ′⍤ඈ3࿆཮¾ඊྡྷ ͢ȭඊྡྷͱՈச࿆Ï᫦3ඊྡྷ Ě3ඊྡྷɬƛ3̺ҋǑà ඈྴˏϔₓṇǷ„ȭ+ඈºጛλɅ IJṇµƧඈºጛŋʌ ਍ţͣƅ᫇ȋňϬ[27-29]4ẋʻĚĭ›ĿʺȪĭɬϏǛĿ@ ໐.ྴˏඊྡྷǶϘ܄ ±ƅṇḿՈ࿆ᯬ̝ࢳʐᜄ੥ʺϣ «P࢑‑ĿƉᰚɳḰơüƄ ƌń̶࢑‑ĿʐɬϏĭ ͢ ‹ǒɀඈ̓ྴˏϔֲɱ੥ṇǷ„ȭ+ඈɅ IJ«ºጛʌz͢ ȌtƧ‑Ŀ—̕Σx′ିሳĭdzọōɳŌ^ẋʻĚĭ Ȉඈ ྴˏඊྡྷǶṇ&Ϙ܄ ඊྡྷ7ⒸՈА└ṇ&±ϖ ĿʺȪĭɬϏǛĿ@඗Ȍ ʺƆྴˏ௤ՈňϬ ΝΈசÏ ྴˏ҉ˊƮɍǜĚǣ4rºጛΝΈ ᢅĚ44 ᫦ Â.dž^சɳ҉Ո̺ҋǑà[30-32]4ปʸ′⍤«P࢑ 2.5 ɪȆēˍFŋɏē Ƿ„ȭ+ඈ3µƧඈ3ป ÖZ„ϬՈ—̕Σx′ିሳĭ ȖzZẴƶ:͢>ᝯË ʸ′⍤ඈ3࿆཮¾ඊྡྷඈǎǒɀඈՈඊྡྷηɋ /& ͯàϬzசɳ҉Ո͏ћ[33]4࿆཮¾ඊྡྷࢿΉdz&ƶĿȴƇ Ƿ„Ոྴˏඈඋඊྡྷ ẟ໐ŻÏĿͱ>Ǜ4۸ūՈྴˏඈ %3(25.2±4.9)%3(27.3±5.6)%3(36.3±4.2)%3(8.7±7.4) (15.2±6.4)% µƧඈඊྡྷηɋ^Ƿ„ȭ+ඈɨṇ:Ŏƅ උ මťǷ„Ոᜄசˈ¿ ęû̺ҋǑà ෗ᢧசɳ҉Ո ºጛɳ͛5 ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈ3ǒɀඈඊྡྷ ÂǕҋ਍[34-35]4IJʌசɳʟȭ࿆཮¾ඊྡྷͣƅǃĐňϬ ηɋ^µƧඈɨṇ:Ŏƅºጛɳ͛5 ǒɀඈඊྡྷη ƽˑ࿆཮¾ඊྡྷࢿΉ͏ћՈάȘ[36]4üǸ ǸƵۘऺŃỞ ¿ˈՈᜄச۔ɋ^ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈɨṇ:Ŏƅºጛɳ͛5 ẋปʸ′⍤Ո˸̠྇ˊ┑ĺ2Ƨசɳ҉̓ ^Ƿ„ȭ+ඈɨṇ µƧඈඊྡྷηºጛʺ̶^µƧඈ ෗ᢧʌᜄசȭ࿆཮¾ඊྡྷՈǃĐ ȴŋ࿆཮¾ඊྡྷࢿΉ͏ ɨṇ ปʸ′⍤ඈ3࿆཮¾ඊྡྷඈ3ǒɀඈඊྡྷηλ ћՈάȘ4 Ʌ ÑǒɀඈλɅżŠº ᢅĚ54 ۘऺº߾ඓẋ⏂࿶◍௤ͼȸ‑Ȍʌசʌ࿆Ģ“ Ụµ

ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH 5329

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ˏᜄசϧඌ̓zǷ ƄẋʻĚĭ›ĿʺȪĭϏĚǛĿPPARY-γ ÑʺƆȭྴ۔d7Ȓ^Ƿ„ȭ+ඈּɨ ͢Ņඈ̓ 20 „Ȩ ẝȴ߾Ụµt£4ඓẋ3ɬՈ͏ћ ^µƧඈɨṇ ௤Ոγͫɳ ┑ĺᜄச ͢ƵỞẋPPARY-γǛĿȴʌ˯້ ाွᜄசţɌŠº[┑ ͢᪙ɀඈŠºĺ ࿆༘௤ˈ¿ปʸ′⍤ẜͣƅ┑ĺᜄϚ൨Ţ›ƣɬĭϏ۔3͏ћඈ̓ zปʸ′⍤ඈǎ࿆཮¾ඊྡྷඈ4^µƧඈɨṇ ปʸ õ:üƄՈňϬ4Dzĉ἗ปʸ′⍤ͣƅ┑࿆3ûω3 ௤3C
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ཱྀˈ¿ǎĿᯬₓ λɅྴˏඈඋඊྡྷ ┑^சɳ҉ õ:̺ҋǑà Ǹி۔Ոྴˏ4ᕁϢ࿆཮¾ඊྡྷћͩ¹̠z᰻ǹ⓺ɉ IJ͢Ȉ η ࿁ƅά͏ћ້̓ ń֎̠«ẠՈ4ƅۘऺº߾࿆཮¾ඊྡྷńĽǎǝâ[ȕ ĺ ྴ ˏ ඈ උ ̺ ҋ ᱏ Ě ü Ƅ CXCL1 3 CXCL2 ǎ ͢ Ǜ Ŀ ͧdzÑń3 dͱ᪵Ȱ Ě&ྴှͱ ͠Ƨඊྡྷ[14-15]4ǎₓ CXCR2ᖏՁƅ͟4 PCR ɑ߾ABCG2 dz[᫇ʐZ᫇ྴှǕྲྀՈḰơüƄ ISL-13IPF-1ʐNGN3 Ȑrdz᪵Ȱ“ϣྴˏ௤3ྴʌᜄ ň້ᯥDzÒŻűǪɝY̓ôκÉαKôκôèɡÒŻűǪ ɝKôκͯʑɡǪɝKǧƨĔΚɡÒŻűKÒŻűfɻKǪɝÔ̖ ச௤ʐϣ⑃õ௤4ň້ɣ14 dČÏȕ࿆ͧ཮¾ඊྡྷ ໐] -֎ΞॅƖuȔŀʃȅRæɻģʕ˵ʩŶ-‚Ȕ «Ở„Ո5 d4ඓẋ25ȕͧɬƛ࿆཮¾ඊྡྷ¹ljťƆ̓ Ēˊ⒲LôκǒlǧSãî͸ŦʦôκȎŨɦ´ͮ͋ǙK ՈʺȪ࿁Ÿ º߾ǔƆՈ̶ȕ ĚȈ࿁4ĉ἗º߾ྴှᾬ ͋Ǚ˴ɡ SYXK20120026ôκˎiȎ;Ƥˋεĝ͸%Θ̠ͮʩ ┨ȒȟŅྴှ ŦʦȎŨȖŶĝȔŀŷ˂ʃõ˼ıΛˋνƽʷôκŦʦÝ dz͹ϣ Ϭྴှᾬˏྴ۔ȒՈɃ┨ ȠȊ˗Y̓ƖuĝĕĴKE`ϝ˽ſȋî˳ſıϠºΓǖȍȍý dzūᜄசʮ̩۔Ոȴǚĭ͏ћ⏂࿶ļነ௤᪵ȰՈசɳ҉Ƀ ˼ŝɏɻģĝLj̧%Θ͑ȷ̢ɻģȎėƤŦʦôκǠˍôκΡ [18-22] Ƿ„ˈ¿ 4 ~QəʷNjŷ˂(ARRIVE ŷ˂) ปʸ′ʒz—̕Σx′ିሳĭ «ẋʻĚĭ›Ŀʺ তɡₑɻģ“1νlˎ CNKI ljɘϡɻˬϗ!ˊȌY̓ 3 ȪĭɬϏǛĿọōɳɬ¬F[23-25]4P5☦ ปʸ′dzָ É(Ɨ ত̲Ǖɻģlˋˍ̔ȅ̓ȻÔDžνňȹȻÔKȐ˾ÌƷɘ ȉ^ẋʻĚĭ›ĿʺȪĭɬϏǛĿּ඗ȌÂū͢ɬϏ ẟ ǷŻ ໐ʺ¤̶࢑ᖏՁᯬՈȌt Âńඊྡྷȭྴˏ௤“ϣǑàr ň້̌ŠÒŻűǪɝƋΡ~˼Lj̧ĝȒɻƏ“˫ĝ^Ƃ̓ɡ dž^ጥወசḰẔʐ-Ϭǎ࿆Ï᫦ẋ࣏ ʺ¤ྴˏ௤γͫ müóQȒɻƏÇΛĝ°ûȕ͛ļœ(Gģαƀ·ļœÿ)βdzΛ ϊcĶuʩʷşLáǫ̂˼̏ͦKæ4ě˺( ɳǪP5☦ ͢dzƯẟGLuf4 ȖüᜬẂ Ưẟඈඋȭ তČƿɻģ“1νÖŽ.ǠȔŀę+NζįƤ1+˵ʩ ጥወசՈʨǚ λḿྴˏ௤ęû ȭǛǃՈྴˏඊྡྷẟᜐ ̠0 ǚ̩ żඌǒɴྴˏ£࿁Ոʮ̩ʐ⑃ƛΝΈǎȋ:ᜄச Ō΢ቻǚ̌ŠŃĆ͙Çǚ;$ɻģKɻģ“1νÖŽ. į Ẃ4ȋ:சɳ҉ՈֲՈ4ปʸ′⍤'ᡅỞẋɬϏḰơü ǠȔŀę+NζįƤ1+˵ʩ̠0ɬœũõʃ̂͠æ̠0

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˵ȅǒüʃ̂3.0ǰċKÝ˾ŨDhĝē˗K [16] Zhu P,Liu J,Shi J,et al.Melatonin protects ADSCs from ROS Í͠ƘNǜ­Ϥ͇ʲĝΆ°ɻˍ`%ΘŐŜ˼ĤĚKȅðÍ͠ and enhances their therapeutic potency in a rat model of Q˽h̴ÇŸ˗ÛÚ]¦ĶíFϗƔIΡƍ4ȶɻˬK myocardial infarction.JCell Mol Med.2015;19(9):2232-2243. Eɡŭ ŻƔDKhȔp
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