孕期高糖对老年子代心血管功能的影响及机制研究

发布时间：2018-07-14 08:02

【摘要】：【目的】研究孕期高糖对老年子代心血管系统功能的影响及相关调控机制。【方法】孕鼠自妊娠第1天至胎鼠出生给予20%蔗糖水和正常食物,其老年子代大鼠为高糖组;正常妊娠的老年子代大鼠为对照组。用血气分析仪和渗透压仪检测血液电解质及血浆渗透压水平;以放射免疫法检测血浆及血管组织Ang II浓度;通过股动、静脉置管术,监测静脉注射Ang II和Losartan后血压的变化;分离制备1)离体胸主动脉环,检测其对AngⅡ、Losartan+Ang II和L-NAME+AngⅡ的应答;2)离体肠系膜小动脉,检测其对AngⅡ、Losartan+Ang II、L-NAME+AngⅡ、Nifedipine+Ang II和Mibefradil+Ang II的应答;用钙离子成像技术检测离体肠系膜小动脉[Ca2+]i对AngⅡ和Losartan+Ang II的应答;以膜片钳全细胞记录模式,检测肠系膜小动脉平滑肌细胞L-Ca及T-Ca电流及其对Ang II和Losartan+Ang II的应答;Real-time PCR检测血管组织中AT1a R、AT1b R、e NOS、Cav1.2、Cav3.1、TBP和GR的m RNA表达;Western Blotting法检测血管组织中AT1R、e NOS、Cav1.2、Cav3.1、TBP和GR的蛋白表达;以染色质免疫共沉淀法检测肠系膜血管组织中AT1a R启动子区域H3Ac、H3K4me3、H3K9me3和H3S10ph的修饰程度,以及与TBP和GR的结合水平。【结果】与对照组相比,孕期高糖的老年子代血液Ang II浓度无显著改变,而胸主动脉、肠系膜小动脉组织中Ang II浓度显著升高,且AT1R的m RNA和蛋白表达均显著增加;静息状态血压显著升高,对外周和中枢Ang II的升压应答显著增强,对外周和中枢Losartan的降压效应显著增强;胸主动脉和肠系膜小动脉对Ang II的收缩应答均显著增强,并可被Losartan抑制;胸主动脉和肠系膜小动脉内皮舒张应答均显著减弱,e NOS的m RNA和蛋白表达均显著下降;肠系膜小动脉[Ca2+]i对AngⅡ的升高应答显著增加,且可被Losartan抑制;肠系膜小动脉平滑肌细胞全细胞T-Ca电流显著增强,L-Ca电流无显著改变,然而L-Ca电流对Ang II的增强应答显著增加,且可被Losartan抑制;肠系膜血管组织中Cav3.1的m RNA和蛋白表达均显著增加,而Cav1.2的m RNA和蛋白表达无显著改变;肠系膜血管组织中AT1a R启动子区域的H3Ac、H3K4me3、和H3S10ph修饰显著增加,而H3K9me3修饰显著下降,TBP和GR的m RNA和蛋白表达均无明显改变,但与AT1a R启动子区域的结合显著增加。【结论】孕期高糖可程序化地影响老年子代的血管功能,其机制与RAS调控血压功能的改变及与血管内皮功能受损、离子通道及表观遗传学机制改变等有关。
[Abstract]:[objective] to study the effects of high glucose concentration during pregnancy on cardiovascular system function of elderly offspring and its related regulatory mechanisms. [methods] pregnant rats were given 20% sucrose water and normal food from the first day of gestation to the birth of fetal rats. The normal pregnant rats were used as the control group. Blood electrolyte and plasma osmotic pressure levels were detected by blood gas analyzer and osmosimeter, Ang II concentrations in plasma and vascular tissues were detected by radioimmunoassay, blood pressure changes after intravenous injection of Ang II and Losartan were monitored by femoral artery and vein catheterization. 1) isolated thoracic aortic rings were isolated and prepared to detect their responses to Ang 鈪，

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