Effect Of Chronic Administration Of L-thyroxine On The Activity Of Ca²⁺/Calmodulin-dependent Protein Kinase Ⅱ In Rats'myocardium

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 (P<0.05 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(P<0.05 ). Furthermore, Western blotting study 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: Our findings indicate that thyroxine decreases the expression level of cardiac CaMKII, but increases the activity of CaMKII in the chronic hyperthyroid-induced hypertrophied heart, suggesting that CaMKII participates the formation and maintenance of cardiac hypertrophy induced by hyperthyroidism in a balance way.