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derived mesenchymal stem cells paracrine effect myocardial i

發(fā)布時間:2016-11-20 14:01

  本文關鍵詞:旁分泌機制在脂肪間充質(zhì)干細胞移植治療心肌梗死中的作用,由筆耕文化傳播整理發(fā)布。


旁分泌機制在脂肪間充質(zhì)干細胞移植治療心肌梗死中的作用

Role of paracrine mechanism in treatment of myocardial infarction by adiposederived mesenchymal stem cell transplantation in mice

[1] [2] [3] [4] [5] [6] [7] [8] [9]

Yang Dezhong, Wang Wei, Wang Wei, Peng Yulan, Huang Haiyun, Wang Yuanyuan, Guo Yanli, Wang Hongyong , Zeng Chunyu ( Department of Cardiology,3 Department of Plastic Surgery,

[1]第三軍醫(yī)大學大坪醫(yī)院野戰(zhàn)外科研究所心血管內(nèi)科,重慶400042; [2]第三軍醫(yī)大學西南醫(yī)院超聲科,重慶400038; [3]第三軍醫(yī)大學大坪醫(yī)院野戰(zhàn)外科研究所整形美容科,重慶400042

文章摘要目的探討旁分泌機制在脂肪間允質(zhì)干細胞(adiopose—derivedstemcells,ADSC)移植治療心肌梗死中的作用。方法原代分離和培養(yǎng)人ADSC,將經(jīng)鑒定的第3~5代的ADSC用于實驗。①用8—10周齡(20~24g)的雄性C57B/L小鼠,結扎左前降支建贏心肌梗北(myocardialinfarction,MI)損傷模型,,實驗分假手術組,MI±DMEM/F12組和MI±ADSC—CM(conditionedmedium,條件培養(yǎng)液)組(n=12)。在MI處理的小鼠心肌梗死邊緣區(qū)分別注射DMEM/F12和ADSC—CM,觀察動物生存率、TTC染色測量心肌梗死面積、超聲評價心功能變化、TUNEL染色檢測心肌細胞凋亡等方法評價心肌梗死的治療效果。②用H202建立乳鼠心肌細胞(neonatalratventricularmyoeytes,NRVM)體外損傷模型,觀察ADSC—CM對心肌細胞的保護作用。實驗分塒照組,H202±DMEM/F12組和H202±ADSC—CM組(n=5)。分別用caspase-3蛋白定鞋和TUNEL染色檢測心肌細胞凋亡。結果①相較于DMEM/F12,ADSC—CM顯著減少心肌梗死面積[(35.3±0.5%)vs(41.7±1.9%)P〈0.05]、提高心功能[EF:(60.4±4.8)%椰(47.2±3.7)%,P〈0.05]、減少梗死邊緣區(qū)心肌細胞凋亡[TUNEL±心肌細胞/10。細胞核:(677.4±64.2)擲(867.3±67.9),P〈0.05];②相對于DMEM/F12,ADSC-CM明顯減少H2O2誘導的心肌細胞凋亡[caspase-3蛋白表達下降;TUNEL陽性率:(58.84±2.19)%擲(71.65±0.86)%,P〈0.05]。結論ADSC—CM通過減少心肌細胞凋亡發(fā)揮對心肌梗死的治療作用;旁分泌作用是ADSC移植治療心肌梗死的重要機制,

AbstrObjective To determine the role of paracrine mechanism in adipose-derived stem cells (ADSC) transplantation-mediated treatment for myocardial infarction (MI). Methods Primarily cultured human ADSC (passage 3 to 5) were characterized and used in the experiments. A total of 36 male C57B/L mice, at an age of 8 to lO weeks, with a weight 20 to 24 g were randomly and equally divided into sham opera- tion group, MI ± DMEM/F12 and MI ± ADSC conditioned medium (ADSC-CM) groups. Mouse model of MI were subjected to MI injury by left descending artery ligation. DMEM/F12 and ADSC-CM were intra-myoeardi- ally injected into the infarct border zone after MI injury. To determine the therapeutic effect, the animal survival rate was observed, myocardial infarct size was measured by TrC staining, cardiac function was evaluated by echocardiography, and cardiomyocyte apoptosis was determined by TUNEL staining. An in vitro cell injury model was established by using neonatal rat ventricular myocytes (NRVMs) with H2 02 treatment, and the cardioprotective effect of ADSC-CM was examined. Results Compared with DMEM/F12, ADSC-CM signifi- cantly reduced the infarct size [ (35.3 ±0.5)% vs (41.7 ± 1.9)%, P 〈0.05], improved cardiac function [ ejection fraction : (60.4 ± 4.8 ) % vs (47.2 ± 3.7 ) % , P 〈 0.05 ], and decreased cardiomyocyte apoptosis in infarct border zone (TUNEL positive cardiomyocytes/106 neuclei: 677.4 ± 64.2 vs 867.3 ±67.9, P 〈0.05). Compared with DMEM/F12, ADSC-CM significantly reduced NRVM apoptosis subjected to H2O2 injury [reduced expression of caspase-3 protein; TUNEL positive rate: (58.84 ±2.19) % vs (71.65 ±0.86)%, P 〈 0.05 ]. Conclusion ADSC-CM exerts therapeutic effect on MI through reducing cardiomyocyte

文章關鍵詞:

Keyword::adipose-derived mesenchymal stem cells paracrine effect myocardial infarction cardiacfunction

課題項目:國家自然科學基金(81100111.31130029);重慶市自然科學基金重點項目(CSTC2011jjB10020);重慶市自然科學基金(CSTC2011jjzt01t8)

 

 


  本文關鍵詞:旁分泌機制在脂肪間充質(zhì)干細胞移植治療心肌梗死中的作用,由筆耕文化傳播整理發(fā)布。



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