甲状腺素对心肌Ca2 钙调蛋白依赖性蛋白激酶Ⅱ的影响-内科学(心血管病)专业论文.docxVIP

华中科技大学硕士学位论文 华 中 科 技 大 学 硕 士 学 位 论 文 PAGE 3 PAGE 3 Effect of chronic administration of L-thyroxine on the activity of Ca2+ /calmodulin-dependent protein kinase II in rats’myocardium Postgraduate: LI Chao Supervisor: Prof. LI Jingdong. Prof.Zhang Jiaming Department of Cardiology, Union Hospital, Tongji Medical Collage, Huazhong University of Science and Technology, Wuhan 430022, P.R China Abstract Objective: To investigate the effect of chronic injection of L-thyroxine on the activity of Ca2+ /calmodulin-dependent protein kinase II (CaMKII) and explore whether CaMKII directly mediates hyperthyroidism-induced cardiac hypertrophy. Methods: Twenty male Sprague–Dawley Rats were randomly divided into hyperthyroid group and control group of 10 animals each. Animal model was obtained by intraperitoneal injection of L-thyroxine or saline vehicle (0.2mg/ (kg·d)), respectively, for 3 months. Heart weight, heart-to-body weight ratio (HW/BW), and left ventricular-to-body weight ratio (LVW/BW) were measured to evaluate cardiac hypertrophy.The ratio of prevascular colleagen area and vascular luminal area (PVCA/VA) was considered to represent myofibrillogenesis. Moreover, the mRNA level of CaMKII and the protein expression level of CaMKII were measured by using Real-time PCR and Western blotting, respectively. Results: Intraperitoneal injection of L-thyroxine for three months significantly increased HW/BW, LVW/BW, PVF/VA and diameter of cardiac myocytes by 1.87-fold, 1.84-fold,1.94-fold and 2.15-fold respectively (P0.05 or 0.01) as compared with the control group. Real-time PCR study revealed that L-thyroxine injection caused a 60﹪ reduction in the mRNA level of cardiac CaMKII(P0.05 ). Furthermore, Western blotting study confirmed that the protein expression level of cardiac CaMKII in L-thyroxine group diminished by 21 ﹪ (P0.05 ), but accompanied by a 1.58-fold enhancement of phosphorylated activity of CaMKII (P0.05 ). Conclusion: Our findings indicate that thyroxine decreases