急性机械牵张对正常和肥厚心脏p38激酶活性的影响

Effects of Acute Mechanical Stretch on the Activity of p38 Kinase in Normal and Hypertrophic Hearts

目的:探讨急性机械牵张对正常心脏和压力超负荷致心肌肥厚心脏的p38激酶活性的影响。方法:40只雌性SD大鼠随机分成4组各10只。其中C、D组行腹主动脉环扎术,造成左心室肥厚的动物模型。用Westernblot方法测定各组大鼠左心室肌的p38激酶活性。结果:术后4周C、D组大鼠有明显的心肌肥厚,心功能处于代偿期。A组即假手术不行急性机械牵张的大鼠左心室肌未见明显的p38激酶活化;而B组即假手术行急性机械牵张、C组术后不行急性机械牵张、D组术后行急性机械牵张的大鼠左心室肌中p38激酶均发生明显活化(P<0.01);其中与C组比较D组p38激酶并未进一步活化。结论:p38激酶信号转导途径是机械牵张导致心肌肥厚的重要环节;但在已肥厚的心脏,p38激酶活性的改变可能能够阻止心脏再受额外刺激而发展为失代偿性肥厚。

Objective: To investigate the effects of acute mechanical stretch on the activities of p38 mitogen activated protein kinase in normal and hypertrophic hearts. Methods: Forty female SD rats were randomly divided into 4 groups (n=10 in each group). The rats in the groups C and D were operated on subtotal abdomial aortic banding to establish models of left ventricular hypertrophy. The activities of p38 kinase in the myocardial tissue samples were detected by Western blot. Results: Four weeks after aortic banding, the left ventricle (LV) in the groups C and D was hypertropic obviously and the functions of hearts of all rats were normal. In the group A (sham-operated group without acute mechanical stretch), there was no activated p38 mitogen activated protein kinase in the LV, while in the group B (sham-operated group with acute mechanical stretch), group C (without acute mechanical stretch after operation), and the group D (with acute mechanical stretch after operation), the activities of p38 kinase in LV were increased significantly (P<0.01). Conclusion: The p38 kinase signal transduction pathway plays an important role in the process of heart hypertrophy induced by mechanical stretch. However, the alternation of p38 kinase activity adaptations in hearts with hypertrophy may have a role to prevent inappropriate excess cardiac hypertrophy in response to additional stimuli.