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目的:探讨Src激酶在高血压所致左心室肥大发病机制中的作用。方法:以自发性高血压大白鼠(SHR)为研究对象,通过免疫荧光标记、共聚焦显微镜观察及蛋白质印迹等方法,检测不同月龄的SHR左心室肥大心肌细胞中Src激酶的表达和定位的变化。结果:蛋白质印迹检测显示,Src激酶在2、6、12和18月龄的SHR组左心室心肌组织抽提的总蛋白匀浆中的表达量与相同月龄的对照Wistar-kyoto(WKY)大鼠组相比较,无明显变化;而在其抽提的胞质蛋白匀浆中和膜蛋白匀浆中,2月龄的SHR组与对照WKY大鼠组相比较,Src激酶的表达无明显差别,但将6、12、18月龄的SHR组分别与相同月龄的WKY大鼠组比较,在胞质蛋白匀浆中Src激酶的表达显著减少(P<0.05),在膜蛋白匀浆中Src的表达则显著增加(P<0.05)。免疫荧光标记也显示,在6、12和18月龄的SHR心肌细胞中出现一些定位变化,主要表现为Src激酶在心肌细胞闰盘的聚集,在心肌细胞闰盘处可观察到较宽的明亮荧光带,这些变化正好与SHR左心室肥大心肌细胞失代偿性重构相吻合。结论:研究结果表明,在高血压所致失代偿性心肌肥大形成和发展的全过程中,存在Src激酶的膜转位,提示心肌细胞中Src激酶信号转导通路可能参与了高血压所致失代偿性左心室肥大的心肌重构过程。
Objective: To investigate the role of Src kinase in the pathogenesis of hypertension-induced left ventricular hypertrophy. Methods: The spontaneous hypertensive rats (SHR) were used as experimental subjects. The expression and localization of Src kinase in left ventricular hypertrophy SHR of SHR at different months of age were detected by immunofluorescence staining, confocal microscopy and Western blotting Variety. Results: Western blotting showed that the expression of Src kinase in total protein homogenate extracted from left ventricular myocardium of SHR group at 2, 6, 12 and 18 months old was significantly higher than that of Wistar-kyoto (WKY) Compared with the control group, the expression of Src kinase in SHR group and control WKY group had no significant difference in the extracted cytoplasmic protein homogenate and membrane protein homogenate , But the expression of Src kinase in cytoplasmic protein homogenate was significantly decreased (P <0.05) compared with WKY rats at 6, 12, and 18-month old in the same age group, respectively Src expression was significantly increased (P <0.05). Immunofluorescent labeling also showed some changes in localization of SHR cardiomyocytes at 6, 12 and 18 months of age, mainly as a result of the accumulation of Src kinase in the intercalated cardiomyocytes, with a broader brightness observed at the intercalated cardiomyocytes Fluorescence bands, these changes coincided with the SHR left ventricular hypertrophy cardiomyocyte compensatory reconstruction consistent. CONCLUSIONS: The results show that Src kinase membrane translocation occurs during the whole process of hypertrophy-induced cardiac hypertrophy and progression, suggesting that Src kinase signal transduction pathway may be involved in the pathogenesis of hypertension Cardiac remodeling in decompensated left ventricular hypertrophy.