Therapeutic adaptation of cardiac expression of adiponectin

目的。我们研究了血管紧张素II受体1型阻滞剂坎地沙坦对急性心肌炎小鼠模型心肌炎损伤的影响。我们假设坎地沙坦通过诱导心脏脂联素的表达来改善心脏损伤。方法与结果。我们通过坎地沙坦诱导心脏脂联素表达来观察小鼠心肌炎引起的心力衰竭的变化。我们腹腔注射C3H小鼠脑心肌炎病毒，然后口服坎地沙坦（10mg /kg/天）或对照药。对照组7天生存率为18%，坎地沙坦组为60%。坎地沙坦组心脏重量/体重比明显低于对照组。坎地沙坦组第7天循环脂联素浓度显著高于对照组（7.91±0.61∶6.04±2.26）。μ g/ml， P<0.05)。坎地沙坦组心脏脂联素mRNA在第7天的比较表达量显著高于对照组（55.4±41.3比5.3±7.7，P<0.05）。免疫组织化学染色和原位杂交显示，坎地沙坦组大鼠第7天心脏有脂联素蛋白和mRNA的表达。口服坎地沙坦可提高病毒性心肌炎小鼠的存活率，减少心肌损伤，并诱导心脏脂联素的表达。脂联素的诱导可能对病毒性心肌炎引起的急性心力衰竭具有心脏保护作用。

Purpose.We examined the effects of the angiotensin II receptor type1 blocker, candesartan, on myocarditis injury in a murine model of acute myocarditis. We hypothesized that candesartan improves cardiac damage by inducing cardiac expression of adiponectin.Methods and Results.We examined changes in heart failure caused by myocarditis in mice by candesartan based on induction of cardiac adiponectin expression. We intraperitoneally injected encephalomyocarditis virus in C3H mice then treated them with oral administration of candesartan (10 mg/kg/day candesartan) or vehicle (Control). The 7 day survival rate was 18% in the Control group, but 60% in the Candesartan group. The heart weight/body weight ratio in the Candesartan group was significantly lower than in the Control group. Circulating adiponectin concentrations on day 7 were significantly higher in the Candesartan group compared with Control group (7.91± 0.61 vs. 6.04±2.26.μ g/ml, P<0.05). Comparative expression of cardiac adiponectin mRNA in the Candesartan group was significantly higher than in the Control group on day 7 (55.4 ± 41.3 vs. 5.3 ± 7.7, P<0.05). Immunohistochemical staining and in situ hybridization showed that cardiac expression of adiponectin protein and mRNA was present in the Candesartan group on day 7.Conclusion.Oral administration of canndesartan improves survival and decreases myocardial damage in mice with viral myocarditits and induces expression of cardiac adiponectin. The induction of adiponectin might provide cardioprotective effects against acute heart failure due to viral myocarditis.