AMPKα2基因缺乏对妊娠性心肌肥厚的影响
发布时间：2018-10-21 07:39
【摘要】：研究目的妊娠可诱导心肌肥厚,但具体分子机制尚不明确。前期研究发现AMPKα2在病理性心肌肥厚的发生发展中具有保护作用。因此,本实验通过建立妊娠模型,观察妊娠期小鼠心脏形态结构的变化,研究AMPKα2基因敲除对妊娠性心肌肥厚的影响及机制,并通过研究AMPKα2在生理性心肌肥厚发生机制中的作用,为AMPKα2是否作为病理性心肌肥厚治疗的特异性靶点提供依据。研究方法建立AMPKα2基因敲除小鼠和野生小鼠妊娠模型,分为野生对照组(WT+NP)、野生妊娠组(WT+P)、AMPKα2基因敲除对照组(KO+NP)、AMPKα2基因敲除妊娠组(KO+P)。运用小鼠心脏超声技术观察四组小鼠受孕前、妊娠中、分娩后三个阶段的心脏变化,WGA染色技术观察四组小鼠妊娠心脏体积的变化,天狼猩红染色技术观察四组小鼠心肌纤维化程度,蛋白免疫印迹法(Western blot)检测小鼠心肌组织蛋白表达变化情况。研究结果(1)超声检测小鼠受孕前、妊娠中、分娩后三个阶段的左心室重量:仅WT+P组和KO+P组妊娠中左心室重量显著高于该组受孕前与分娩后左心室重量(P0.01);WT+P组妊娠中左心室重量显著高于WT+NP组(P0.01);KO+P组妊娠中左心室重量显著高于KO+NP组(P0.01);KO+P组妊娠中左心室重量显著高于WT+P组(P0.05);KO+P组分娩后左心室重量显著高于KO+NP组(P0.05)。(2)WGA染色检测心肌细胞横截面积:与WT+NP组相比,WT+P组的心肌细胞横截面积显著增加(P0.01);与KO+NP组相比,KO+P组的心肌细胞横截面积显著增加(P0.01);与WT+P组相比,KO+P组的心肌细胞横截面积显著增加(P0.01)。(3)与WT+NP组相比,WT+P组心室/体重的比值和左心室/体重的比值显著增加(P0.01);与KO+NP组相比,KO+P组心室/体重的比值、左心室/体重的比值和左心室/胫骨长度的比值显著增加(P0.01);与WT+P组相比,KO+P组心室/体重的比值、左心室/体重的比值和左心室/胫骨长度的比值均显著增加(P0.01)。(4)各实验组均未见明显心肌纤维化现象。(5)与WT+NP组相比,WT+P组的AMPKα磷酸化水平显著增加(P0.01);与KO+NP组相比,KO+P组的AMPKα磷酸化水平显著增加(P0.01);与WT+P组相比,KO+P组的AMPKα磷酸化水平显著增加(P0.01)。(6)与KO+NP组相比,KO+P组的ACC磷酸化水平显著减少(P0.01);与WT+NP组相比,KO+NP组的ACC磷酸化水平显著增加(P0.01);与WT+P组相比,KO+P组的ACC磷酸化水平显著减少(P0.01)。研究结论(1)妊娠可诱导心肌肥厚,该过程未发生纤维化等病理性改变。(2)AMPKα2基因敲除加重了妊娠诱导的心肌肥厚,表现为心脏重量的增加和心肌细胞横截面积的增大。(3)妊娠性心肌肥厚与AMPK/ACC信号传导通路密切相关,妊娠期心脏适应性改变可激活AMPK信号通路,并有可能起到保护心脏的作用。
[Abstract]:Objective pregnancy can induce myocardial hypertrophy, but the molecular mechanism is unclear. Previous studies have found that AMPK 伪 2 plays a protective role in the occurrence and development of pathological myocardial hypertrophy. Therefore, by establishing a pregnancy model, we observed the changes of cardiac morphology and structure in pregnant mice, studied the effect and mechanism of AMPK 伪 2 knockout on pregnant myocardial hypertrophy, and studied the role of AMPK 伪 2 in the pathogenesis of physiologic myocardial hypertrophy. To provide evidence for AMPK 伪 2 as a specific target for the treatment of pathological myocardial hypertrophy. Methods pregnancy models of AMPK 伪 2 knockout mice and wild mice were established and divided into wild control group (WT NP), wild pregnancy group (WT P), AMPK 伪 2 gene knockout control group (KO NP), AMPK 伪 2 gene knockout pregnancy group (KO P). The changes of heart in four groups of mice were observed by echocardiography before conception, during pregnancy and after delivery. The changes of cardiac volume of pregnant mice in four groups were observed by WGA staining. The degree of myocardial fibrosis was observed by Sirius red staining and the changes of myocardial protein expression were detected by Western blot (Western blot). Results (1) Ultrasound was used to detect the pregnant mice before and during pregnancy. Left ventricular weight in three postpartum stages: left ventricular weight in WT P group and KO P group was significantly higher than that before and after delivery in WT P group and KO P group (P0.01); WT P group was significantly higher than WT NP group in pregnancy group (P0.01); KO P group). Left ventricular weight in pregnancy was significantly higher than that in KO NP group (P0.01); KO P group was significantly higher than that in WT P group (P0.05); KO P group was significantly higher than KO NP group (P0.05). (2) WGA staining to detect myocardial cell cross-sectional area: compared with WT NP group The cross-sectional area of cardiomyocytes in, WT P group was significantly increased (P0.01), that in, KO P group was significantly higher than that in KO NP group (P0.01), and that in, KO P group was significantly higher than that in WT P group (P0.01). (3) compared with that in WT NP group (P0.01). (3). The ventricular / body weight ratio and the left ventricular / body weight ratio in P group were significantly increased (P0.01), and the ventricular / body weight ratio in, KO P group was significantly higher than that in KO NP group. The ratio of left ventricle / body weight and left ventricle / tibia length increased significantly (P0.01), and the ratio of ventricular / body weight of, KO P group was higher than that of WT P group. The ratio of left ventricle / body weight and the ratio of left ventricle / tibia length were significantly increased (P0.01). (4). (5) compared with the WT NP group, the AMPK 伪 phosphorylation level in the, WT P group was significantly higher than that in the WT NP group (P0.01), and the phase in the KO NP group was significantly higher than that in the KO NP group (P0.01). The level of AMPK 伪 phosphorylation in, KO P group was significantly higher than that in, KO P group (P0.01), the AMPK 伪 phosphorylation level in, KO P group was significantly higher than that in WT P group (P0.01). (6), the ACC phosphorylation level in, KO P group was significantly lower than that in KO NP group (P0.01), and the ACC phosphorylation level in, KO NP group was significantly lower than that in WT NP group (P0.01). The level of ACC phosphorylation in, KO P group was significantly lower than that in WT P group (P0.01). Conclusion (1) Myocardial hypertrophy can be induced by pregnancy without pathological changes such as fibrosis. (2) AMPK 伪 2 gene knockout exacerbates the myocardial hypertrophy induced by pregnancy. (3) gestational myocardial hypertrophy is closely related to AMPK/ACC signal transduction pathway. During pregnancy, cardiac adaptation may activate AMPK signaling pathway and may protect the heart.
【学位授予单位】：上海体育学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.252
本文编号：2284412
[Abstract]:Objective pregnancy can induce myocardial hypertrophy, but the molecular mechanism is unclear. Previous studies have found that AMPK 伪 2 plays a protective role in the occurrence and development of pathological myocardial hypertrophy. Therefore, by establishing a pregnancy model, we observed the changes of cardiac morphology and structure in pregnant mice, studied the effect and mechanism of AMPK 伪 2 knockout on pregnant myocardial hypertrophy, and studied the role of AMPK 伪 2 in the pathogenesis of physiologic myocardial hypertrophy. To provide evidence for AMPK 伪 2 as a specific target for the treatment of pathological myocardial hypertrophy. Methods pregnancy models of AMPK 伪 2 knockout mice and wild mice were established and divided into wild control group (WT NP), wild pregnancy group (WT P), AMPK 伪 2 gene knockout control group (KO NP), AMPK 伪 2 gene knockout pregnancy group (KO P). The changes of heart in four groups of mice were observed by echocardiography before conception, during pregnancy and after delivery. The changes of cardiac volume of pregnant mice in four groups were observed by WGA staining. The degree of myocardial fibrosis was observed by Sirius red staining and the changes of myocardial protein expression were detected by Western blot (Western blot). Results (1) Ultrasound was used to detect the pregnant mice before and during pregnancy. Left ventricular weight in three postpartum stages: left ventricular weight in WT P group and KO P group was significantly higher than that before and after delivery in WT P group and KO P group (P0.01); WT P group was significantly higher than WT NP group in pregnancy group (P0.01); KO P group). Left ventricular weight in pregnancy was significantly higher than that in KO NP group (P0.01); KO P group was significantly higher than that in WT P group (P0.05); KO P group was significantly higher than KO NP group (P0.05). (2) WGA staining to detect myocardial cell cross-sectional area: compared with WT NP group The cross-sectional area of cardiomyocytes in, WT P group was significantly increased (P0.01), that in, KO P group was significantly higher than that in KO NP group (P0.01), and that in, KO P group was significantly higher than that in WT P group (P0.01). (3) compared with that in WT NP group (P0.01). (3). The ventricular / body weight ratio and the left ventricular / body weight ratio in P group were significantly increased (P0.01), and the ventricular / body weight ratio in, KO P group was significantly higher than that in KO NP group. The ratio of left ventricle / body weight and left ventricle / tibia length increased significantly (P0.01), and the ratio of ventricular / body weight of, KO P group was higher than that of WT P group. The ratio of left ventricle / body weight and the ratio of left ventricle / tibia length were significantly increased (P0.01). (4). (5) compared with the WT NP group, the AMPK 伪 phosphorylation level in the, WT P group was significantly higher than that in the WT NP group (P0.01), and the phase in the KO NP group was significantly higher than that in the KO NP group (P0.01). The level of AMPK 伪 phosphorylation in, KO P group was significantly higher than that in, KO P group (P0.01), the AMPK 伪 phosphorylation level in, KO P group was significantly higher than that in WT P group (P0.01). (6), the ACC phosphorylation level in, KO P group was significantly lower than that in KO NP group (P0.01), and the ACC phosphorylation level in, KO NP group was significantly lower than that in WT NP group (P0.01). The level of ACC phosphorylation in, KO P group was significantly lower than that in WT P group (P0.01). Conclusion (1) Myocardial hypertrophy can be induced by pregnancy without pathological changes such as fibrosis. (2) AMPK 伪 2 gene knockout exacerbates the myocardial hypertrophy induced by pregnancy. (3) gestational myocardial hypertrophy is closely related to AMPK/ACC signal transduction pathway. During pregnancy, cardiac adaptation may activate AMPK signaling pathway and may protect the heart.
【学位授予单位】：上海体育学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.252
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