【摘要】：【目的】研究孕期高糖對老年子代心血管系統(tǒng)功能的影響及相關(guān)調(diào)控機(jī)制。【方法】孕鼠自妊娠第1天至胎鼠出生給予20%蔗糖水和正常食物,其老年子代大鼠為高糖組;正常妊娠的老年子代大鼠為對照組。用血氣分析儀和滲透壓儀檢測血液電解質(zhì)及血漿滲透壓水平;以放射免疫法檢測血漿及血管組織Ang II濃度;通過股動、靜脈置管術(shù),監(jiān)測靜脈注射Ang II和Losartan后血壓的變化;分離制備1)離體胸主動脈環(huán),檢測其對AngⅡ、Losartan+Ang II和L-NAME+AngⅡ的應(yīng)答;2)離體腸系膜小動脈,檢測其對AngⅡ、Losartan+Ang II、L-NAME+AngⅡ、Nifedipine+Ang II和Mibefradil+Ang II的應(yīng)答;用鈣離子成像技術(shù)檢測離體腸系膜小動脈[Ca2+]i對AngⅡ和Losartan+Ang II的應(yīng)答;以膜片鉗全細(xì)胞記錄模式,檢測腸系膜小動脈平滑肌細(xì)胞L-Ca及T-Ca電流及其對Ang II和Losartan+Ang II的應(yīng)答;Real-time PCR檢測血管組織中AT1a R、AT1b R、e NOS、Cav1.2、Cav3.1、TBP和GR的m RNA表達(dá);Western Blotting法檢測血管組織中AT1R、e NOS、Cav1.2、Cav3.1、TBP和GR的蛋白表達(dá);以染色質(zhì)免疫共沉淀法檢測腸系膜血管組織中AT1a R啟動子區(qū)域H3Ac、H3K4me3、H3K9me3和H3S10ph的修飾程度,以及與TBP和GR的結(jié)合水平�！窘Y(jié)果】與對照組相比,孕期高糖的老年子代血液Ang II濃度無顯著改變,而胸主動脈、腸系膜小動脈組織中Ang II濃度顯著升高,且AT1R的m RNA和蛋白表達(dá)均顯著增加;靜息狀態(tài)血壓顯著升高,對外周和中樞Ang II的升壓應(yīng)答顯著增強(qiáng),對外周和中樞Losartan的降壓效應(yīng)顯著增強(qiáng);胸主動脈和腸系膜小動脈對Ang II的收縮應(yīng)答均顯著增強(qiáng),并可被Losartan抑制;胸主動脈和腸系膜小動脈內(nèi)皮舒張應(yīng)答均顯著減弱,e NOS的m RNA和蛋白表達(dá)均顯著下降;腸系膜小動脈[Ca2+]i對AngⅡ的升高應(yīng)答顯著增加,且可被Losartan抑制;腸系膜小動脈平滑肌細(xì)胞全細(xì)胞T-Ca電流顯著增強(qiáng),L-Ca電流無顯著改變,然而L-Ca電流對Ang II的增強(qiáng)應(yīng)答顯著增加,且可被Losartan抑制;腸系膜血管組織中Cav3.1的m RNA和蛋白表達(dá)均顯著增加,而Cav1.2的m RNA和蛋白表達(dá)無顯著改變;腸系膜血管組織中AT1a R啟動子區(qū)域的H3Ac、H3K4me3、和H3S10ph修飾顯著增加,而H3K9me3修飾顯著下降,TBP和GR的m RNA和蛋白表達(dá)均無明顯改變,但與AT1a R啟動子區(qū)域的結(jié)合顯著增加�！窘Y(jié)論】孕期高糖可程序化地影響老年子代的血管功能,其機(jī)制與RAS調(diào)控血壓功能的改變及與血管內(nèi)皮功能受損、離子通道及表觀遺傳學(xué)機(jī)制改變等有關(guān)。
[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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