目的:探索异丙肾上腺素(isoprenaline,ISO,非选择性β-肾上腺素受体激动剂)诱导FVB/N小鼠心脏重塑的实验条件.方法:经皮下注射和埋泵控释两种途径给予FVB/N小鼠ISO诱导心脏肥大和纤维化,将每种给药途径的FVB/N小鼠随机分为ISO组和对照组.皮下注射给药途径:ISO组皮下注射IS0 14 d,对照组注射生理盐水;皮下埋泵给药途径:ISO组皮下埋泵控释给予IS0 14 d,对照组做假手术.两种给药途径ISO剂量均为30 mg/(kg·d).采用心脏重量与胫骨长度比值(心胫比)、小动物超声心动图检测小鼠心室壁厚度等指标衡量心脏肥大程度.使用苦味酸-天狼猩红染色方法检测胶原沉积面积.结果:ISO皮下注射不能诱导FVB/N小鼠明显的心脏肥大和纤维化,且实验终点前有50%小鼠死亡.ISO皮下埋泵控释给药诱导FVB/N小鼠出现显著的心脏肥大,ISO组小鼠心胫比显著高于对照组[(10.60±0.40) mg/mmvs.(7.93±0.19) mg/mm,P<0.001],ISO组小鼠的左心室舒张末期后壁厚度显著高于对照组[(0.87±0.03)mm vs.(0.68 ±0.06) mm,P=0.0116],但ISO不能引起明显的心脏纤维化,小鼠全部存活.结论:IS0 30 mg/(kg·d)皮下埋微量泵2周可成功诱导FVB/N小鼠心脏肥大模型.
Objective:To investigate the condition of isoprenaline (ISO)-induced cardiac hypertrophy in the FVB/N mouse.Methods:ISO [30 mg/(kg · d)] was administered either by daily subcutaneous injection,or by continuous infusion via an implanted osmotic minipump.The mice in each mode of administration were randomly divided into two groups.For subcutaneous injection:the mice received ISO or saline through daily subcutaneous injection for 2 weeks.The mice for minipump:the mice received continuous infusion of ISO via an implanted osmotic minipump for 2 weeks,or received sham operation as the control to mimipump.The ratio of heart weight to tibia length (HW/TI),the diastolic left ventricular posterior wall thickness (dLVPW) were used to indicate cardiac hypertrophy.Interstitial fibrosis was examined with picrosirius red staining.Results:ISO [30 mg/(kg · d)] administered by daily subcutaneous injection did not lead to cardiac hypertrophy or fibrosis in the FVB/N mice,and 50% of the mice died before the end point.The mice receiving ISO via minipumps showed significant increase in HW/TI [(10.60±0.40) mg/mm vs.(7.93±0.19) mg/mm,P<0.001] and dLVPW [(0.87 ±0.03)mm vs.(0.68 ±0.06)mm,P =0.0116].ISO administered via minipumps did not induce cardiac fibrosis.All the mice in this group survived to the end point.Conclusion:ISO [30 mg/(kg · d)] administered by continuous infusion via a minipump for 2 weeks can lead to significant cardiac hypertrophy.