【摘要】：研究目的妊娠可誘導(dǎo)心肌肥厚,但具體分子機(jī)制尚不明確。前期研究發(fā)現(xiàn)AMPKα2在病理性心肌肥厚的發(fā)生發(fā)展中具有保護(hù)作用。因此,本實(shí)驗(yàn)通過(guò)建立妊娠模型,觀察妊娠期小鼠心臟形態(tài)結(jié)構(gòu)的變化,研究AMPKα2基因敲除對(duì)妊娠性心肌肥厚的影響及機(jī)制,并通過(guò)研究AMPKα2在生理性心肌肥厚發(fā)生機(jī)制中的作用,為AMPKα2是否作為病理性心肌肥厚治療的特異性靶點(diǎn)提供依據(jù)。研究方法建立AMPKα2基因敲除小鼠和野生小鼠妊娠模型,分為野生對(duì)照組(WT+NP)、野生妊娠組(WT+P)、AMPKα2基因敲除對(duì)照組(KO+NP)、AMPKα2基因敲除妊娠組(KO+P)。運(yùn)用小鼠心臟超聲技術(shù)觀察四組小鼠受孕前、妊娠中、分娩后三個(gè)階段的心臟變化,WGA染色技術(shù)觀察四組小鼠妊娠心臟體積的變化,天狼猩紅染色技術(shù)觀察四組小鼠心肌纖維化程度,蛋白免疫印跡法(Western blot)檢測(cè)小鼠心肌組織蛋白表達(dá)變化情況。研究結(jié)果(1)超聲檢測(cè)小鼠受孕前、妊娠中、分娩后三個(gè)階段的左心室重量:僅WT+P組和KO+P組妊娠中左心室重量顯著高于該組受孕前與分娩后左心室重量(P0.01);WT+P組妊娠中左心室重量顯著高于WT+NP組(P0.01);KO+P組妊娠中左心室重量顯著高于KO+NP組(P0.01);KO+P組妊娠中左心室重量顯著高于WT+P組(P0.05);KO+P組分娩后左心室重量顯著高于KO+NP組(P0.05)。(2)WGA染色檢測(cè)心肌細(xì)胞橫截面積:與WT+NP組相比,WT+P組的心肌細(xì)胞橫截面積顯著增加(P0.01);與KO+NP組相比,KO+P組的心肌細(xì)胞橫截面積顯著增加(P0.01);與WT+P組相比,KO+P組的心肌細(xì)胞橫截面積顯著增加(P0.01)。(3)與WT+NP組相比,WT+P組心室/體重的比值和左心室/體重的比值顯著增加(P0.01);與KO+NP組相比,KO+P組心室/體重的比值、左心室/體重的比值和左心室/脛骨長(zhǎng)度的比值顯著增加(P0.01);與WT+P組相比,KO+P組心室/體重的比值、左心室/體重的比值和左心室/脛骨長(zhǎng)度的比值均顯著增加(P0.01)。(4)各實(shí)驗(yàn)組均未見(jiàn)明顯心肌纖維化現(xiàn)象。(5)與WT+NP組相比,WT+P組的AMPKα磷酸化水平顯著增加(P0.01);與KO+NP組相比,KO+P組的AMPKα磷酸化水平顯著增加(P0.01);與WT+P組相比,KO+P組的AMPKα磷酸化水平顯著增加(P0.01)。(6)與KO+NP組相比,KO+P組的ACC磷酸化水平顯著減少(P0.01);與WT+NP組相比,KO+NP組的ACC磷酸化水平顯著增加(P0.01);與WT+P組相比,KO+P組的ACC磷酸化水平顯著減少(P0.01)。研究結(jié)論(1)妊娠可誘導(dǎo)心肌肥厚,該過(guò)程未發(fā)生纖維化等病理性改變。(2)AMPKα2基因敲除加重了妊娠誘導(dǎo)的心肌肥厚,表現(xiàn)為心臟重量的增加和心肌細(xì)胞橫截面積的增大。(3)妊娠性心肌肥厚與AMPK/ACC信號(hào)傳導(dǎo)通路密切相關(guān),妊娠期心臟適應(yīng)性改變可激活A(yù)MPK信號(hào)通路,并有可能起到保護(hù)心臟的作用。
[Abstract]:Objective pregnancy can induce myocardial hypertrophy, but the molecular mechanism is unclear. Previous studies have found that AMPK 偽 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 偽 2 knockout on pregnant myocardial hypertrophy, and studied the role of AMPK 偽 2 in the pathogenesis of physiologic myocardial hypertrophy. To provide evidence for AMPK 偽 2 as a specific target for the treatment of pathological myocardial hypertrophy. Methods pregnancy models of AMPK 偽 2 knockout mice and wild mice were established and divided into wild control group (WT NP), wild pregnancy group (WT P), AMPK 偽 2 gene knockout control group (KO NP), AMPK 偽 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 偽 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 偽 phosphorylation in, KO P group was significantly higher than that in, KO P group (P0.01), the AMPK 偽 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 偽 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.
【學(xué)位授予單位】：上海體育學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R714.252

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