二氮嗪预处理缺氧复氧大鼠心肌微血管内皮细胞PI3K、Akt、FKN mRNA的表达

Effects of diazoxide pretreatment on the mRNA expression of PI3K,Akt,and FKN in rat myocardium microvascular endothelial cells exposed to hypoxia-reoxygenation

背景:在缺氧复氧早期,促使心肌微血管内皮细胞增殖的措施,涉及一系列相关基因的改变和受多种基因调控。目的:观察二氮嗪预处理对缺氧复氧大鼠心肌微血管内皮细胞增殖和PI3K、Akt和FKNmRNA表达的影响。方法:培养SD大鼠心肌微血管内皮细胞,按照不同的干预方式将细胞随机均分为正常对照组、缺氧/复氧组、二氮嗪组、二氮嗪+阻断剂组。观察凋亡细胞形态、活力及PI3K、Akt和FKNmRNA转录水平。结果与结论:与正常对照组比较,缺氧/复氧组细胞增殖率显著降低、Akt和FKN显著升高(P<0.01)。与缺氧/复氧组比较,二氮嗪组细胞增殖率显著升高(P<0.05);PI3K和Akt显著升高、FKN显著降低(P<0.01)。二氮嗪+阻断剂组取消了二氮嗪的作用,与缺氧/复氧组比较差异无显著性意义。说明二氮嗪预处理通过促使细胞增殖,上调PI3K、AktmRNA表达、下调FKNmRNA表达而实现对缺氧复氧心肌微血管内皮细胞损伤的保护。

BACKGROUND： In the early stage of hypoxia-reoxygenation, the measures of promoting proliferation myocardium microvascular endothelial cells （MMECs） involve a series of related genetic changes, which are regulated by multiple genes. OBJECTIVE： To investigate the effects of diazoxide pretreatment on the mRNA expression of PI3K, Akt and FKN as we as pro/iferation of rat MMECs exposed to hypoxJa-reoxygenation. METHODS： The SD rat MMECs were randomly divided into normal control group, hypoxia-reoxygenation group diazoxide pretreatment group and diazoxide pretreatment＋5-hydroxydecanoate group. Cell vitality, morphology, apoptotic rate and mRNA expression of PI3K, Akt and FKN were detected. RESULTS AND CONCLUSION： Compared with the normal control group, the cell proliferation rate was significantly decreased and the mRNA expression of FKN and Akt was up-regulated in the hypoxia-reoxygenation group （P 〈 0.01 ）. Compared with the hypoxia-reoxygenation group, the cell proliferation rate was significantly increased （P 〈 0.05）, and the mRNA expression of PI3K and Akt was up-regulated obviously, while FKN mRNA expression was significantly decreased in diazoxide pretreatment group （P 〈 0.01）. Diazoxide pretreatment＋5-hydroxydecanoate group called off diazoxide pretreatment-induced changes, and did not differ from the hypoxia-reoxygenation group. These findings suggest that diazoxide pretreatment can promote cell proliferation and up-regulate the mRNA expression of PI3K and Akt as well as decrease FKN mRNA expression protect rat MMECs from hypoxia-reoxygenation.