NF-κB参与Akt信号途径激活诱导的心肌肥大

NF-κB activation participates in the activated Akt signaling induced cardiac hypertrophy in vivo

目的 :探讨NF -κB信号在Akt信号途径激活诱导的心肌肥大发生机制中所起的作用。方法 :以缩窄SD大鼠升主动脉诱导的心肌肥大和心脏特异性表达的caAkt转基因小鼠为模型 ,采用EMSA检测心肌组织中NF-κB结合活性 ,应用Westernblot方法分析心肌组织中phospho -Akt和phospho-IκBα的表达水平。结果 :①缩窄大鼠升主动脉 3周后 ,心脏重量 /体重比值高于假手术组 34 5 % (P <0 0 1) ,而且肥大心肌组织中p -Akt蛋白表达明显高于假手术组 (P <0 0 1)。②caAkt转基因小鼠心脏明显肥大 ,其心肌组织中NF -κB活性比野生型小鼠高 5 6 7 86 %(P <0 0 1) ,同时心肌组织中IκBα的磷酸化水平也明显高于野生型小鼠 (P <0 0 1)。结论 :NF -κB介入到Akt信号途径激活所致的心肌肥大发生发展过程中。

AIM: To explore whether NF-κB activation participates in the activated Akt signaling-induced cardiac hypertrophy in vivo. METHODS: We used two in vivo models of cardiac hypertrophy, namely, aortic banding in Sprague-Dawley rats for 3 weeks and transgenic mice with cardiac specific expression of constitutively active Akt (caAkt). Electrophoretic mobility shift assay (EMSA) was used to determine NF-κB binding activity with nuclear proteins extracted from heart tissues. Western blots were performed to examine the phosphorylation of Akt and phosphor-IκBα with appropriate specific anti-phospho antibodies. RESULTS: ① The heart weight/body weight (HW/BW) ratio was significantly increased by 34 5% ( P <0 01) in aortic banded 3 weeks rats compared to sham operated control. The level of phosphor-Akt in hypertrophic heart was significantly increased compared to sham operated control ( P <0 01). ② The ratio of HW/BW in caAkt transgenic mice was significantly increased by 123 4% ( P< 0 01), compared to wild type control. NF-κB binding activity and the level of phospho-IκBα were also significantly increased in caAkt mice compared to wild type control ( P <0 01). CONCLUSION: NF-κB activation participates in the activated Akt signaling-induced cardiac hypertrophy in vivo.