超声联合SDF-1微泡对糖尿病性心肌病大鼠心肌损伤的保护作用
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摘要
目的研究超声联合基质细胞衍生因子-1(SDF-1)微泡对糖尿病性心肌病大鼠心肌损伤的保护作用。方法将40只SD大鼠随机分为空白组、模型组、SDF-1组、SDF-1+超声组、微泡+超声组,每组8只。除空白组外,其余组均采用高脂饲料喂养和腹腔注射1%链脲佐菌素(STZ)方法制备糖尿病性心肌病模型。造模成功后,SDF-1组经尾静脉输入SDF-1溶液10 ng/kg;SDF-1+超声组经尾静脉输入SDF-1溶液10ng/kg,然后采用2%戊巴比妥钠1 mL/kg腹腔注射麻醉大鼠,利用超声治疗仪辐照大鼠心前区10 min;微泡+超声组经尾静脉输入含有10 ng/kg SDF-1的微泡混合液,超声照射同SDF-1+超声组。干预4 d后,留取血清标本用于检测肌酸激酶(CK)、乳酸脱氢酶(LDH)、心肌肌钙蛋白I(cT nI)水平;干预8周后,超声心动图检测各组大鼠左心室舒张末期内径(LVIDd)、左心室舒张末压(LVEDP)和左心室射血分数(LVEF),Western blot法检测各组心肌组织中CXC族趋化因子受体4(CXCR4)蛋白表达情况,实时定量PCR法检测各组心肌组织中转化生长因子β1(TGF-β1)mR NA表达情况。结果干预4 d后,各组血清CK、LDH和cT nI水平比较差异均无统计学意义(P均>0.05)。干预8周后,各干预组LVIDd、LVEDP均明显低于模型组(P均<0.05),LVEF均明显高于模型组(P均<0.05),微泡+超声组各指标改善情况均明显优于SDF-1组和SDF-1+超声组(P均<0.05);模型组及各干预组CXCR4蛋白表达水平和TGF-β1mR NA表达水平均明显高于空白组(P均<0.05),各干预组TGF-β1mR NA表达水平均明显低于模型组(P均<0.05);微泡+超声组CXCR4蛋白表达水平明显高于其他组(P均<0.05),TGF-β1mR NA表达水平均明显低于SDF-1组和SDF-1+超声组(P均<0.05)。结论超声联合SDF-1微泡可延缓糖尿病性心肌病大鼠心肌纤维化。
Objective It is to investigate the protective effects of ultrasound and stroma cell-derived factor-1( SDF-1)microbubbles on myocardial injury in the rats with diabetic cardiomyopathy. Methods 40 SD rats were randomly divided into blank group( group A),model group( group B) and SDF-1 group( group C),SDF-1 plus ultrasound group( group D),microbubbles plus ultrasound group( group E),each group had 8 rats. All the rats except in group A were given high fat diet and 1% STZ by intraperitoneal injection to establish diabetic cardiomyopathy models. Group B,group C,group D and group E were treated with respective therapy. After treatment for 4 days,the serum examples were collected for myocardial enzyme testing including CK,LDH,c Tn I; after treatment for 8 days,LVIDd and LVEDP and LVEF of the rats in each group were detected by echocardiography,the protein expression of CXCR4 in each group were detected by Western blot,the expression of TGF-β1 gene m RNA was detected by real-time quantitative PCR. Results After treatment for 4 days,there was no significant difference in the levels of serum CK,LDH and c Tn I among every group( P > 0. 05). After treatment for8 days,LVIDd,LVEDP in every treatment group were lower and LVEF was higher than that in model group( P < 0. 05),and the improvements in group E were better than that in group C,group D( P < 0. 05); the expression of CXCR4 and TGF-β1 m RNA in group B and every treatment group was higher than that in group A( P < 0. 05),furthermore,the expression of TGF-β1 m RNA in every treatment group was lower than that in group B( P < 0. 05),the expression of CXCR4 in group E was higher than that in the other treatment groups( P < 0. 05),that of TGF-β1 m RNA in group E was lower than that in group C and group D( P < 0. 05). Conclusion Ultrasound and SDF-1 microbubbles can delay myocardial fibrosis in rats with diabetic cardiomyopathy.
Objective It is to investigate the protective effects of ultrasound and stroma cell-derived factor-1( SDF-1)microbubbles on myocardial injury in the rats with diabetic cardiomyopathy. Methods 40 SD rats were randomly divided into blank group( group A),model group( group B) and SDF-1 group( group C),SDF-1 plus ultrasound group( group D),microbubbles plus ultrasound group( group E),each group had 8 rats. All the rats except in group A were given high fat diet and 1% STZ by intraperitoneal injection to establish diabetic cardiomyopathy models. Group B,group C,group D and group E were treated with respective therapy. After treatment for 4 days,the serum examples were collected for myocardial enzyme testing including CK,LDH,c Tn I; after treatment for 8 days,LVIDd and LVEDP and LVEF of the rats in each group were detected by echocardiography,the protein expression of CXCR4 in each group were detected by Western blot,the expression of TGF-β1 gene m RNA was detected by real-time quantitative PCR. Results After treatment for 4 days,there was no significant difference in the levels of serum CK,LDH and c Tn I among every group( P > 0. 05). After treatment for8 days,LVIDd,LVEDP in every treatment group were lower and LVEF was higher than that in model group( P < 0. 05),and the improvements in group E were better than that in group C,group D( P < 0. 05); the expression of CXCR4 and TGF-β1 m RNA in group B and every treatment group was higher than that in group A( P < 0. 05),furthermore,the expression of TGF-β1 m RNA in every treatment group was lower than that in group B( P < 0. 05),the expression of CXCR4 in group E was higher than that in the other treatment groups( P < 0. 05),that of TGF-β1 m RNA in group E was lower than that in group C and group D( P < 0. 05). Conclusion Ultrasound and SDF-1 microbubbles can delay myocardial fibrosis in rats with diabetic cardiomyopathy.
引文
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[12]Dong F,Harvey J,Finan A,et al.Myocardial CXCR4 expression is required for mesenchymal stem cell mediated repair following acute myocardial infarction[J].Circulation,2012,126(3):314-324
[13]Zamani M,Prabhakaran MP,Thian ES,et al.Controlled delivery of stromal derived factor-1 alpha from poly lactic-co-glycolic acid core-shell particles to recruit mesenchymal stem cells for cardiac regeneration[J].J Colloid Interf-ace Sci,2015,451:144-152
[14]Won YW,Patel AN,Bull DA.Cell surface engineering to enhance mesenchymal stem cell migration toward an SDF-1 gradient[J].Biomaterials,2014,35(21):5627-5635
[15]Meng XM,Tang PM,Li J,et al.TGF-β/Smad signaling in renal fibrosis[J].Front Physiol,2015,6:82
[2]杨跃进,王红,宋光远.糖尿病心肌病[J].中国糖尿病杂志,2012,20(10):794-796
[3]Jujo K,Li M,Sekiguchi H,et al.Cxc-chemokine receptor 4 antagonist amd 3100 promotes cardiac functional recovery after schemia/reperfusion injury via endothelial nitric oxide syntliase-dependent mechanism clinical perspective[J].Circulation,2013,127:63-73
[4]李小林,范忠才,白雪.骨髓间充质干细胞移植心肌梗死大鼠的心功能[J].中国组织工程研究,2013,17(10):1761-1765
[5]刘文旗,戴红艳,邢明青,等.糖尿病心肌病动物模型的建立[J].中国组织工程研究,2015,19(27):4265-4270
[6]Trachanas K,Sideris S,Aggeli C,et al.Diabetic cardiomyopathy:from pathophysiology to treatment[J].Hellenic J Cardiol,2014,55(5):411-421
[7]范忠伟,谭美云.调控SDF-1/CXCR4轴在骨髓间充质干细胞向心肌梗死部位归巢中的研究现状[J].泸州医学院学报,2016,39(3):287-290
[8]Przybyt E,Harmsen MC.Mesenchymal stem cell:promising for myocardial regeneration?[J].Curr Stem Cell Res Ther,2013,8(4):270-277
[9]陈荟竹,郭应坤,宁刚.间充质干细胞移植治疗心肌梗死的研究进展[J].生物医学工程学杂志,2014,31(4):939-944
[10]Wan C,Qian J,Li F,et al.Ultrasound-targeted microbubble destruction enhances polyethylenimine-mediated gene transfection in vitro in human retinal pigment epithelial cells and in vivo in rat retina[J].Mol Med Rep,2015,12(2):2835-2841
[11]沈祥波,魏芹,童嘉毅.超声联合一氧化氮微泡对大鼠心肌组织的生物学效应[J].南京医科大学学报:自然科学版,2014,34(2):135-138
[12]Dong F,Harvey J,Finan A,et al.Myocardial CXCR4 expression is required for mesenchymal stem cell mediated repair following acute myocardial infarction[J].Circulation,2012,126(3):314-324
[13]Zamani M,Prabhakaran MP,Thian ES,et al.Controlled delivery of stromal derived factor-1 alpha from poly lactic-co-glycolic acid core-shell particles to recruit mesenchymal stem cells for cardiac regeneration[J].J Colloid Interf-ace Sci,2015,451:144-152
[14]Won YW,Patel AN,Bull DA.Cell surface engineering to enhance mesenchymal stem cell migration toward an SDF-1 gradient[J].Biomaterials,2014,35(21):5627-5635
[15]Meng XM,Tang PM,Li J,et al.TGF-β/Smad signaling in renal fibrosis[J].Front Physiol,2015,6:82