The Cardiovascular Institute, Tokyo, Japan.
J Cardiol. 2011 Sep;58(2):131-6. doi: 10.1016/j.jjcc.2011.06.003. Epub 2011 Jul 30.
Diabetes mellitus promotes atrial structural remodeling, thereby producing atrial arrhythmogenicity, where advanced glycation endproducts (AGEs) and their receptor (RAGE) are implicated to play a role in the pathogenesis.
We investigated the effects of candesartan, an angiotensin type II receptor blocker, on the diabetes-induced atrial structural change.
Diabetes was induced in 8-week-old female Sprague-Dawley rats by intraperitoneal injection of streptozotocin at 70 mg/kg. Osmotic pumps were simultaneously set to infuse candesartan at a subdepressor dose of 0.05 mg/kg/day. Twelve weeks after the induction of diabetes, the blood glucose and glycated hemoglobin A1c were significantly higher in streptozotocin-injected rats than those in control rats, and were not affected by candesartan treatment. The atria of diabetic rats showed remarkable diffuse interstitial fibrosis with more enhanced protein expressions of RAGE and connective tissue growth factor (CTGF) compared with control ones. The treatment with candesartan significantly reduced CTGF expression and effectively suppressed the development of fibrotic deposition in diabetic animals.
Candesartan reduced CTGF expression and attenuated the fibrosis in diabetic rat atria. These results implied the protective effects of candesartan on diabetes-related atrial arrhythmias.
糖尿病可促进心房结构重塑，从而产生致心律失常性，其中晚期糖基化终产物（AGEs）及其受体（RAGE）被认为在发病机制中起作用。
我们研究了血管紧张素 II 受体阻滞剂坎地沙坦对糖尿病诱导的心房结构变化的影响。
8 周龄雌性 Sprague-Dawley 大鼠通过腹腔注射链脲佐菌素 70mg/kg 诱导糖尿病。同时设置渗透型泵以每天 0.05mg/kg 的亚降压剂量输注坎地沙坦。糖尿病诱导 12 周后，与对照组相比，链脲佐菌素注射大鼠的血糖和糖化血红蛋白 A1c 显著升高，坎地沙坦治疗并未影响其血糖水平。与对照组相比，糖尿病大鼠的心房表现出明显弥漫性间质纤维化，RAGE 和结缔组织生长因子（CTGF）的蛋白表达增强。坎地沙坦治疗可显著降低 CTGF 表达，并有效抑制糖尿病动物纤维沉积的发展。
坎地沙坦降低了 CTGF 的表达，并减轻了糖尿病大鼠心房的纤维化。这些结果暗示了坎地沙坦对糖尿病相关心房性心律失常的保护作用。
