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目的高血压和高血脂均可导致动脉粥样硬化(As)的发生,罹患两种疾病的患者,病情进展更快且预后更差。弄清高血压和高血脂共同的致病机制,对于As的防治有重要的指导意义。方法应用机械牵张力和/或氧化型低密度脂蛋白(oxidized lowdensity lipoprotein,ox-LDL)刺激静息培养的大鼠血管平滑肌细胞(VSMC),Western Blotting检测ERK1/2的磷酸化水平;RT-PCR检测细胞血凝素样氧化型低密度脂蛋受体1(LOX-1)的表达;LOX-1-siRNA预处理细胞,观察LOX-1基因沉默对机械牵张力和/或ox-LDL处理的VSMC ERK1/2磷酸化的影响。结果机械牵张力和/或ox-LDL均可激活ERK1/2,引起明显的ERK1/2磷酸化增加,而两种因素共同存在时ERK1/2激活更加明显。ox-LDL和机械牵张力均可分别上调LOX-1 mRNA表达水平,前者在第3 h达到峰值,随后维持在一较高的水平;后者在第6 h达到峰值,随后逐渐下降,24 h恢复到基础水平。此外,LOX-1-siRNA预处理可以减少LOX-1 mRNA量,进而导致机械牵张力和/或ox-LDL诱导的ERK1/2磷酸化的抑制。结论 LOX-1受体可同时介导机械牵张力和ox-LDL引起的VSMC ERK1/2的磷酸化,当机械牵张力和ox-LDL两者同时存在时对ERK1/2的激活呈现明显地协同促进作用。本研究可望为深入探讨高血压伴随高血脂协同引起血管重构的机制研究提供重要的实验室资料。
Purpose Both hypertension and hyperlipidemia lead to the development of atherosclerosis (As). Patients with both diseases develop faster and have worse prognosis. To clarify the common pathogenic mechanism of hypertension and hyperlipidemia has important guiding significance for the prevention and treatment of As. Methods Rat VSMCs were cultured with mechanical stretch and / or oxidized low density lipoprotein (ox-LDL). The phosphorylation of ERK1 / 2 was detected by Western Blotting. RT- PCR was used to detect the expression of LOX-1. LOX-1 siRNA was used to pretreat LOX-1 gene to observe the effect of LOX-1 gene silencing on mechanical stretch and / or ox-LDL The effect of phosphorylation of VSMC ERK1 / 2. Results Both mechanical stretch and / or ox-LDL could activate ERK1 / 2, causing a significant increase of phosphorylation of ERK1 / 2. ERK1 / 2 activation was more obvious when both factors were coexisted. Ox-LDL and mechanical stretch could up-regulate the expression of LOX-1 mRNA respectively. The former peaked at 3 h and then maintained at a high level. The latter peaked at 6 h and then decreased gradually. After 24 h Restore to the basic level. In addition, LOX-1-siRNA pretreatment can reduce the amount of LOX-1 mRNA, leading to mechanical stretch and / or ox-LDL-induced inhibition of ERK1 / 2 phosphorylation. CONCLUSIONS: LOX-1 receptor mediates both mechanical stretch and phosphorylation of ERK1 / 2 in VSMCs induced by ox-LDL. Synergistically, ERK1 / 2 activation appears synergistically when both mechanical stretch and ox-LDL are present enhancement. This study is expected to provide important laboratory data for further research on the mechanism of hypertension associated with hyperlipidemia caused by vascular remodeling.