异丙肾上腺素诱导FVB/N小鼠心脏肥大模型的建立

Establishment of a FVB / N mouse model of cardiac hypertrophy by isoprenaline

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ISO 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ISO 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/mm vs.(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:ISO 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.