抑制法尼基焦磷酸合成酶改善2型糖尿病大鼠左心室重构与心脏功能

Inhibition of Farnesyl Pyrophosphate Synthase Ameliorating Left Ventricular Remodeling and Cardiac Dysfunction in Rats with Type 2 Diabetes

目的探讨抑制法尼基焦磷酸合成酶对改善2型糖尿病大鼠左心室重构与心功能的影响。方法采用高脂高糖饮食加一次性腹腔注射小剂量链脲佐菌素(STZ 30mg/kg)建立2型糖尿病模型。健康雄性SD大鼠30只随机分成正常对照组(control组,n=10)、糖尿病组(DM组,n=10)、糖尿病+伊班膦酸钠组(DM+IB组,n=10)。建模成功后DM+IB组SD大鼠连续16周每天皮下注射5微克/千克剂量伊班膦酸钠溶液,control和DM组大鼠在相同位置注射相等剂量的0.9%氯化钠注射液。实验21周后分别对3组SD大鼠行心脏超声和血流动力学测定,HE染色观察心肌细胞形态横截面大小,Masson复合染色检测心肌组织胶原纤维沉积程度。结果与对照组相比,DM组大鼠左心室内径增大、室间隔及左心室后壁显著增厚、心功能降低、心肌细胞明显肥大、心肌间质及心肌血管周围胶原纤维沉积显著增多(P<0.01);DM+IB组大鼠虽出现上述结构及功能改变,但与DM组相比上述情况均有明显改善(P<0.05)。结论抑制法尼基焦磷酸合成酶在一定程度上可改善糖尿病心肌病大鼠左室重构与心脏功能。

Objective To investigate whether inhibition of farnesyl pyrophosphate synthase can ameliorate left ventricular remodeling and cardiac dysfunction in rats with type 2 diabetes. Methods The experimental type 2 diabetic model was established by high fat and high-carbonhydrate diet combined with one-time intraperitoneal injection of low dose streptozotocin( STZ30 mg / kg). Thirty healthy male Sprague-Dawley rats were randomly divided into control group( n = 10),diabetic group( n =10) and diabete with ibandronate treated group( DM + IB group,n = 10). While the model was successfully eastablished,the rats in DM + IB group were injected by subcutaneous with 5 ug / kg of sodium ibandronate for each day for sixteen weeks,and the rats in diabetic group and control groups were received equal volume of saline solution. 21 weeks later,the hemodynamics and echocardiographic for the experimental rats were obtained. Masson composite staining was used to investigate the expression and distribution of collagen in cardiac muscle tissue,and hematoxylin-eosin staining was used to evaluate the intersecting surface of cellular morphology in myocardium. The collagen volume fraction( CVF) was evaluated by Semiquantitative analysis. Results Compared with control group,the left ventricular cavity dilatation,septal and left ventricular posterior wall thickening,cardiomyocyte hypertrophy,myocardial interstitial and perivascular collagen deposition in diabetic group increased significantly,while the cardiac function decreased significantly( P < 0. 01). However,ibandronate treatment ameliorated the structural and functional changes compared with diabetic group. Conclusions Inhibition of farnesyl pyrophosphate synthase by ibandronate ameliorates left ventricular remodeling and cardiac dysfunction in rats with type 2 diabetes.