| 张瑞萍,刘福垒.上调Klotho基因表达对心肌梗死大鼠心功能及心肌纤维化的影响[J].安徽医药,2018,22(9):1665-1669. |
| 上调Klotho基因表达对心肌梗死大鼠心功能及心肌纤维化的影响 |
| Effects of up-regulation expression of Klotho gene on cardiac function and myocardial fibrosis in rats with myocardial infarction |
| 投稿时间：2017-03-14 |
| DOI： |
| 中文关键词: Klotho基因 心肌梗死 心功能 心肌纤维化 大鼠 |
| 英文关键词: Klotho gene Myocardial infarction Cardiac function Myocardial fibrosis Rat |
| 基金项目:山东省自然科学基金(ZR2014HL108) 上调Klotho基因表达对心肌梗死大鼠心功能及心肌纤维化的影响张瑞萍1,刘福垒2 (1.洛阳市第一人民医院检验科,河南 洛阳 471002；2.泰安市中心医院,山东 泰安 271000) |
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| 中文摘要: |
| 目的 探讨上调Klotho基因表达对心肌梗死大鼠心功能及心肌纤维化的影响。方法 60只雄性SD大鼠,按随机数字表法分为假手术组、模型组、空白质粒组和Klotho转染组,制备大鼠急性心肌梗死模型,Klotho转染组分别于左心室游离壁上、下、左、右四个部位进行局部注射携带Klotho基因的质粒,模型组和空白质粒组则分别将等量的生理盐水和空白质粒进行局部注射。各组14 d后,利用超声心动图对存活51只大鼠心功能进行检测,TTC法检测大鼠心肌梗死面积,采用免疫组织化学和Masson三色染色法检测各组大鼠心肌组织病理学和纤维化,利用实时荧光定量PCR技术和Western blot法分别对各组大鼠心肌组织中Klotho、转化生长因子β1(TGF-β1)、结缔组织生长因子(CTGF)基因和蛋白表达进行检测。结果 模型组左心射血分数(LVEF)、短轴缩短率(FS)、心室收缩末期内径(LVDs)和左心室舒张末期内径(LVDd)分别为(49.82±3.41)%、(48.07±2.36)%、(6.09±0.80)mm和(8.39±0.47)mm,空白质粒组则分别为(52.20±2.55)%、(29.95±2.39)%、(6.17±0.82)mm和(8.30±0.62)mm,与模型组和空白质粒组相比,Klotho转染组大鼠LVEF和FS[(68.67±3.76)%、(40.08±3.83)%]均升高,而LVDs和LVDd[(5.51±0.59)mm、(6.74±0.50)mm]均降低(F=306.935、117.659、24.530、58.090,P<0.001)；假手术组大鼠心肌梗死面积为0.00%,模型组和空白质粒组大鼠心肌梗死面积分别为(37.34±0.52)%、(36.51±0.48)%,两组均高于Klotho转染组的(24.82±0.24)%(F=44.195,P<0.001)；与模型组和空白质粒组相比,Klotho转染组间质纤维化面积(21.62±2.38)%减少(F=52.942,P<0.001)；模型组大鼠心肌组织中Klotho、TGF-β1、CTGF基因和蛋白相对表达量分别(1.31±0.12)和(0.52±0.07)、(1.98±0.17)和(0.86±0.09)、(2.38±0.09)和(0.92±0.11),空白质粒组则分别为(1.33±0.16)和(0.54±0.13)、(1.96±0.16)和(0.85±0.11)、(2.43±0.10)和(0.88±0.14),与模型组和空白质粒组相比,Klotho转染组大鼠心肌组织中Klotho基因和蛋白相对表达量[(1.80±0.16)、(0.68±0.07)]升高(F=110.443、26.336,P<0.001),而TGF-β1、CTGF基因和蛋白相对表达量[(1.52±0.12)和(0.50±0.05)、(1.89±0.12)和(0.70±0.13)]均降低(F=94.409和125.076、362.350和74.300,P<0.001)。结论 上调Klotho基因表达可有效改善心肌梗死大鼠心功能,减轻心肌纤维化,其机制可能与抑制TGF-β1、CTGF基因表达有关。 |
| 英文摘要: |
| Objective To investigate the effects of up-regulation of Klotho gene expression on cardiac function and myocardial fibrosis in rats with myocardial infarction.Methods 60 male SD rats were randomly divided into sham operation group,model group,Klotho transfection group and blank plasmid group.The acute myocardial infarction models were established.In the Klotho transfection group,the Klotho gene plasmid vectors were injected into the infracted part on the left ventricular wall.And in the model group and the blank plasmid group,the same amount of saline and blank plasmid were injected,respectively.After 14d,the cardiac function was detected by using echocardiography.The myocardial infarct size was measured by TTC.The myocardial histopathology and fibrosis were detected in each group.The expressions of Klotho,transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) genes and proteins were detected by using real-time quantitative PCR and Western blot,respectively.Results The left heart ejection fraction (LVEF),short axis shortening (FS),ventricular contraction end diameter (LVDs) and left ventricular end diastolic diameter (LVDd) in the model group were (49.82±3.41)%,(48.07±2.36)%,(6.09±0.80) mm and (8.39±0.47) mm,respectively,while in the blank plasmid group were (52.20±2.55)%,(29.95±2.39)%,(6.17±0.82) mm and (8.30±0.62) mm,respectively.Compared with the model group and blank plasmid group,LVEF and FS in the Ad-Klotho group [(68.67±3.76)%,(40.08±3.83)%] were increased,while the LVDs and LVDd [(5.51±0.59) mm,(6.74±0.50) mm] were decreased (F=306.935,7.659,4.530 and 58.090,P< 0.001).The infarct size in the sham operation group was 0.00%,in the model group and blank plasmid group were (37.34±0.52)% and (36.51±0.48)%,respectively,which were higher than the Klotho transfection group,which was (24.82±0.24)% (F=44.195,P<0.001).Compared with the model group and blank plasmid group,the area of interstitial fibrosis in the Ad-Klotho group was decreased,which was (21.62±2.38)% (F= 52.942,P< 0.001).The relative expression levels of Klotho,TGF-β1 and CTGF genes and proteins in the model group were (1.31±0.12) and (0.52±0.07),(1.98±0.17) and (0.86±0.09),(2.38±0.09) and (0.92±0.11),respectively,while in the blank plasmid group were (1.33±0.16) and (0.54±0.13),(1.96±0.16) and (0.85±0.11),(2.43±0.10) and (0.88±0.14),respectively.Compared with the model group and blank plasmid group,the relative expression levels of Klotho gene and protein in the Klotho transfection group [(1.80±0.16),(0.68±0.07)] were increased (F=110.443,6.336,P< 0.001),while the relative expression levels of TGF-β1 and CTGF genes and proteins [(1.52±0.12) and (0.50±0.05),(1.89±0.12) and (0.70±0.13)] were decreased (F=94.409 and 125.076,2.350 and 74.300,P< 0.001).Conclusion Up-regulation expression of Klotho gene could improve cardiac function and myocardial fibrosis in rats with myocardial infarction.The mechanism might be related to the inhibition the expressions of TGF-β1 and CTGF genes. |
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