有氧运动对压力超负荷小鼠心功能及心肌纤维化影响的实验研究
发布时间：2019-02-16 08:35
【摘要】：目的:高血压由于长期的压力超负荷导致心肌间质纤维增生,从而使心功能下降。长期有氧运动可以改善心功能,其机制是否与有氧运动能改善心肌纤维化有关,热休克转录因子1(HSF1)是否在运动的保护机制中起调节作用都有待研究。因此本文采用主动脉缩窄手术制备小鼠高血压模型,探讨长期有氧运动对高血压小鼠心功能及心肌纤维化作用的影响。为高血压病的运动治疗提供实验依据。方法:8周龄BALB/c雄性小鼠60只,随机分为3组每组20只,分别为正常组(CON)、手术组(TAC)和手术+运动组(TAE)。TAC和TAE组小鼠进行升主动脉缩窄手术(transverse aortic constriction,TAC),建立高血压模型。TAE组小鼠手术4天后进行0坡度跑台跑步,采用渐进递增运动负荷运动时间方案,自12米/分×30min递增到15米/分×60min,第5周持续采用15米/分×60min,5次/周,一共10周。待TAE组10周有氧运动结束后3组小鼠分别采用Vevo770超声诊断仪和30MHz高频探头进行心脏超声检测,测量左室收缩期内径(left ventricular internal dimension systole,LVIDs)、左室舒张期内径(left ventricular internal dimension diastole,LVIDd)、左室射血分数(left ventricular ejection fraction,EF%)和心率(Heart rate,HR)等指标。血流动力学检查采用Millar导管测量右颈主动脉压。取材后立即用电子天平称量小鼠心脏重量,计算心重体重比。病理染色采用HE染色和Masson染色,分别观察小鼠心肌肥厚情况和心肌纤维化程度。同时采用实时荧光定量PCR技术(Quantitative Real-time PCR)检测小鼠热休克转录因子1(Heat shock transcription factor 1,HSF1)基因的表达量。结果:实验过程中小鼠运动状态良好,体重稳步增长。主动脉测压结果显示:与CON组相比,TAC组血压升高了大约60mmHg,10周有氧运动后TAE组血压明显下降(P0.05)。超声心电图的结果显示,TAC组相对于CON组小鼠的左室射血分数(LVEF)降低(P0.01),左室舒张末期内径(LVIDd)和左室收缩末期内径(LVIDs)升高(P0.01);TAE组相对于TAC组小鼠的左室射血分数(LVEF)升高(P0.05),左室舒张末期内径(LVIDd)和左室收缩末期内径(LVIDs)降低(P0.01)。小鼠心脏重量指数结果显示,TAC组的心重指数明显大于CON组(P0.01),TAE组的心重体重比小于TAC组(P0.05)。HE病理染色结果得出:TAC组心肌细胞明显比CON组肥大,而运动后的TAE组心肌横截面积小于TAC组。Masson病理染色结果显示:TAC组心肌纤维化明显多于CON组,而TAE组相较TAC组,纤维化程度减弱。从HSF1的基因表达量可以得出:TAC组小鼠HSF1的表达量相较CON组减少(P0.01),而TAE组却显著高于TAC组小鼠HSF1的表达量(P0.01)。结论:1、通过主动脉缩窄手术建立的压力超负荷模型以及手术后有氧运动模型建立是成功。2、10周压力超负荷使心肌肥厚、心肌纤维增生从而导致心功能下降,通过有氧运动后能有效缓解心功能的下降、减弱纤维化程度。3、压力超负荷致心肌组织中的HSF1下降,而有氧运动上调心肌HSF1基因表达,推测这是减少心肌纤维化、提高心功能的可能机制。
[Abstract]:Objective: To reduce the cardiac function due to long-term pressure overload. The long-term aerobic exercise can improve the heart function, and whether the mechanism is related to the aerobic exercise can improve the myocardial fibrosis, and whether the heat shock transcription factor 1 (HSF1) plays an important role in the mechanism of motion protection is to be studied. Therefore, the effect of long-term aerobic exercise on the heart function and myocardial fibrosis of the mice with high blood pressure was discussed. and provides an experimental basis for the exercise therapy of the hypertension. Methods: 60 BALB/ c male mice were randomly divided into three groups: normal group (CON), operation group (TAC) and operation + exercise group (TAE). After 4 days of operation in the TAE group, the 0-grade running platform was run, and the progressive incremental moving-load movement time scheme was used, and it was increased from 12 m/ min to 15 m/ min for 60min, and the 5-week duration was 15 m/ min to 60min and 5 times/ week for a total of 10 weeks. After the 10-week aerobic exercise of the TAE group, three groups of mice were detected by the Vevo 770 ultrasonic diagnostic apparatus and the 30MHz high-frequency probe, respectively, and the left ventricular systolic internal diameter (LVIDs), the left ventricular diastolic diameter (LVIDd) and the left ventricular ejection fraction were measured. EF%) and heart rate (HR). The right-neck aortic pressure was measured by a Milar catheter using a Milar catheter. The weight of the heart weight of the mice was weighed using an electronic balance, and the weight ratio of the heart weight was calculated. The myocardial hypertrophy and the degree of myocardial fibrosis were observed by HE staining and Masson staining. At the same time, the expression of heat shock transcription factor 1 (HSF1) gene in mice was detected by the real-time fluorescence quantitative PCR (RT-PCR). Results: In the course of the experiment, the exercise status of the mice was good and the body weight increased steadily. The results of aortic pressure test showed that the blood pressure of the TAC group increased by about 60mmHg compared with that of the CON group, and the blood pressure of the TAE group decreased significantly after 10 weeks of aerobic exercise (P0.05). The results of echocardiography showed that the left ventricular ejection fraction (LVEF) of the TAC group was lower than that of the CON group (P0.01), the left ventricular end-diastolic diameter (LVIDd) and the left ventricular end-systolic diameter (LVIDs) increased (P0.01), and the left ventricular ejection fraction (LVEF) of the TAE group relative to the TAC group mice (P0.05). The left ventricular end-diastolic diameter (LVIDd) and the left ventricular end-systolic diameter (LVIDs) decreased (P0.01). The heart weight index of the TAC group was significantly higher than that of the CON group (P0.01), and the weight ratio of the center weight of the TAE group was lower than that of the TAC group (P0.05). The results of HE and pathology showed that the cardiac myocyte of the TAC group was significantly higher than that of the CON group, and the cross-sectional area of the myocardial cross-section of the TAE group after the exercise was smaller than that of the TAC group. The results of Masson's pathological staining showed that the myocardial fibrosis in the TAC group was significantly higher than that of the CON group, while the group with the TAE group had a higher degree of fibrosis and the degree of fibrosis decreased. The expression of HSF1 in the TAC group was lower than that of the CON group (P0.01), while the group of TAE was significantly higher than that of the mice in the TAC group (P0.01). Conclusion: 1. The pressure overload model established by the narrow operation of the aorta and the establishment of the aerobic exercise model after operation are successful. To decrease the degree of fibrosis. 3, the HSF1 in the myocardial tissue decreased with the pressure overload, and the aerobic exercise upregulates the expression of the myocardial HSF1 gene, which is a possible mechanism to reduce the myocardial fibrosis and improve the heart function.
【学位授予单位】：上海师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：G804.2
本文编号：2424257
[Abstract]:Objective: To reduce the cardiac function due to long-term pressure overload. The long-term aerobic exercise can improve the heart function, and whether the mechanism is related to the aerobic exercise can improve the myocardial fibrosis, and whether the heat shock transcription factor 1 (HSF1) plays an important role in the mechanism of motion protection is to be studied. Therefore, the effect of long-term aerobic exercise on the heart function and myocardial fibrosis of the mice with high blood pressure was discussed. and provides an experimental basis for the exercise therapy of the hypertension. Methods: 60 BALB/ c male mice were randomly divided into three groups: normal group (CON), operation group (TAC) and operation + exercise group (TAE). After 4 days of operation in the TAE group, the 0-grade running platform was run, and the progressive incremental moving-load movement time scheme was used, and it was increased from 12 m/ min to 15 m/ min for 60min, and the 5-week duration was 15 m/ min to 60min and 5 times/ week for a total of 10 weeks. After the 10-week aerobic exercise of the TAE group, three groups of mice were detected by the Vevo 770 ultrasonic diagnostic apparatus and the 30MHz high-frequency probe, respectively, and the left ventricular systolic internal diameter (LVIDs), the left ventricular diastolic diameter (LVIDd) and the left ventricular ejection fraction were measured. EF%) and heart rate (HR). The right-neck aortic pressure was measured by a Milar catheter using a Milar catheter. The weight of the heart weight of the mice was weighed using an electronic balance, and the weight ratio of the heart weight was calculated. The myocardial hypertrophy and the degree of myocardial fibrosis were observed by HE staining and Masson staining. At the same time, the expression of heat shock transcription factor 1 (HSF1) gene in mice was detected by the real-time fluorescence quantitative PCR (RT-PCR). Results: In the course of the experiment, the exercise status of the mice was good and the body weight increased steadily. The results of aortic pressure test showed that the blood pressure of the TAC group increased by about 60mmHg compared with that of the CON group, and the blood pressure of the TAE group decreased significantly after 10 weeks of aerobic exercise (P0.05). The results of echocardiography showed that the left ventricular ejection fraction (LVEF) of the TAC group was lower than that of the CON group (P0.01), the left ventricular end-diastolic diameter (LVIDd) and the left ventricular end-systolic diameter (LVIDs) increased (P0.01), and the left ventricular ejection fraction (LVEF) of the TAE group relative to the TAC group mice (P0.05). The left ventricular end-diastolic diameter (LVIDd) and the left ventricular end-systolic diameter (LVIDs) decreased (P0.01). The heart weight index of the TAC group was significantly higher than that of the CON group (P0.01), and the weight ratio of the center weight of the TAE group was lower than that of the TAC group (P0.05). The results of HE and pathology showed that the cardiac myocyte of the TAC group was significantly higher than that of the CON group, and the cross-sectional area of the myocardial cross-section of the TAE group after the exercise was smaller than that of the TAC group. The results of Masson's pathological staining showed that the myocardial fibrosis in the TAC group was significantly higher than that of the CON group, while the group with the TAE group had a higher degree of fibrosis and the degree of fibrosis decreased. The expression of HSF1 in the TAC group was lower than that of the CON group (P0.01), while the group of TAE was significantly higher than that of the mice in the TAC group (P0.01). Conclusion: 1. The pressure overload model established by the narrow operation of the aorta and the establishment of the aerobic exercise model after operation are successful. To decrease the degree of fibrosis. 3, the HSF1 in the myocardial tissue decreased with the pressure overload, and the aerobic exercise upregulates the expression of the myocardial HSF1 gene, which is a possible mechanism to reduce the myocardial fibrosis and improve the heart function.
【学位授予单位】：上海师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：G804.2
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