羧基末端调节蛋白对压力负荷诱导小鼠心肌肥厚的保护作用

发布时间：2018-06-30 17:50

  本文选题：心肌肥厚 + 心脏功能　； 参考：《吉林大学》2017年硕士论文

【摘要】：目的:探究羧基末端调节蛋白(CTMP)对压力负荷诱导心肌肥厚小鼠的影响以及机制研究。方法:本实验应用雄性、动物背景为C57BL/6的小鼠(8-10周龄,体重在23.5-27.5g)。选取α-MHC-MCM小鼠、CTMP-Flox小鼠和CTMP-CKO小鼠、CTMPTG小鼠,随机分为两组,一组行主动脉缩窄术(aortic biding,AB),作为AB组,另外一组作为对照组(Sham组)。4周后,检测两组小鼠的心功能,解剖后测量小鼠心脏质量(HW),肺部质量(LW),胫骨长度(TL)。并计算两组小鼠心脏重量与体重的比值(HW/BW),心脏重量与胫骨长度的比值(HW/TL),以及肺脏重量与体重的比值(LW/BW)。在HE染色和PSR染色基础上,观察并测量心肌细胞横截面积和心肌纤维化程度。应用Real-time PCR技术检测反映代表心肌肥厚和心肌纤维化标志物的表达水平(ANP、BNP、β-MHC;Collagen Iα、CollagenⅢ、CTGF)。应用Western blot技术,检测CTMP在MAPK和Akt通路的蛋白表达水平,探究CTMP影响心肌肥厚的作用机制。结果:1、在AB组,CTMP-CKO小鼠相较于对照组(α-MHC-MCM小鼠、CTMPFlox小鼠)心肌肥厚程度明显增加,心肌细胞横截面积和心肌胶原蛋白含量增加,心功能明显恶化,以及心肌肥厚标志物和纤维化标志物明显增加。2、在AB组,CTMP-TG小鼠相较于CTMP-NTG小鼠(α-MHC-MCM小鼠)心肌肥厚程度明显减弱,心肌细胞横截面积减小,心肌胶原蛋白含量降低,心功能好转,以及心肌肥厚标志物和纤维化标志物明显降低。3、在信号通路研究中,CTMP能够影响Akt及其下游分子磷酸化水平,表明CTMP通过作用于Akt通路影响心肌肥厚。结论:CTMP能够与Akt通路相互作用,影响AKT-GSK3β信号通路,进而影响小鼠的心肌肥厚程度、心肌细胞横截面积、心肌纤维化程度以及心功能。
[Abstract]:Aim: to investigate the effect and mechanism of carboxyl terminal regulatory protein (CTMP) on myocardial hypertrophy induced by pressure load in mice. Methods: male C57BL / 6 mice (8-10 weeks old, weight 23.5-27.5g) were used. The 伪 -MHC-MCM mice CTMP-Flox and CTMP-CKO mice were randomly divided into two groups: one group was treated with aortic coarctation (AB) as AB group, the other group was used as control group (Sham group) after 4 weeks, the cardiac function of the two groups was measured. The heart mass (HW), lung mass (LW) and tibia length (TL) were measured after dissection. The ratio of heart weight to body weight (HW / BW), the ratio of heart weight to tibia length (HW / TL), and the ratio of lung weight to body weight (LW / BW) were calculated. On the basis of HE staining and PSR staining, the cross sectional area of myocardial cells and the degree of myocardial fibrosis were observed and measured. Real-time PCR technique was used to detect the expression level of myocardial hypertrophy and myocardial fibrosis markers (ANP-BNPs, 尾 -MHC-Collagen I 伪 Collagen 鈪，

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