Abstract:AIM: To investigate the effect of chronic injection of L-thyroxine on Ca2+/calmodulin-dependent protein kinaseⅡ (CaMKII) and to explore whether CaMKII directly mediates hyperthyroidism-induced cardiac hypertrophy. METHODS: Twenty male Sprague-Dawley rats were randomly divided into hyperthyroid group and control group with 10 animals each. The animal model was produced by intraperitoneal injection of L-thyroxine (0.2 mg·kg-1·d-1) for 3 months. The control animals only received saline vehicle in the same procedures. Heart weight (HW), heart-to-body weight ratio (HW/BW), left ventricular-to-body weight ratio (LVW/BW) and diameter of cardiac myocytes were measured to evaluate cardiac hypertrophy. The ratio of perivascular collagen area to vascular luminal area (PVCA/VA) was used to represent myocrdial fibrosis. Moreover, the mRNA expression of CaMKII and the protein level of CaMKII were measured by real-time RT-PCR and Western blotting, respectively. RESULTS: Intraperitoneal injection of L-thyroxine for 3 months significantly increased HW/BW, LVW/BW, PVCA/VA and diameter of cardiac myocytes by 1.87, 1.84, 1.94 and 2.15 folds, respectively (P<0.05 or P<0.01) as compared with control group. The results of real-time RT-PCR revealed that L-thyroxine injection caused a 60% reduction in the mRNA level of cardiac CaMKII (P<0.05). Furthermore, the results of Western blotting confirmed that the protein expression level of cardiac CaMKII in L-thyroxine group diminished by 21% (P<0.05), but accompanied by a 1.58-fold enhancement of phosphorylated activity of CaMKII (P<0.05). CONCLUSION: Thyroxine decreases the expression level of cardiac CaMKII and increases the activity of CaMKII in the chronic hyperthyroid-induced hypertrophic heart, suggesting that CaMKII participates in the formation and maintenance of cardiac hypertrophy induced by hyperthyroidism in a balanced way.
李超, 刘善红, 张家明, 刘敏, 李景东. 长期甲状腺素刺激对大鼠心肌Ca /钙调蛋白依赖性蛋白激酶Ⅱ的影响[J]. 中国病理生理杂志, 2012, (1): 147-151.
LI Chao, LIU Shan-hong, ZHANG Jia-min, LIU Ming, LI Jing-dong. Effect of chronic administration of L-thyroxine on Ca2+/calmodulin-dependent protein kinaseⅡ in rat myocardium. Chin J Pathophysiol, 2012, (1): 147-151.
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