腹腔注射异丙肾上腺素诱导FVB/N小鼠心脏重塑模型

Establishment of cardiac remodeling model in FVB/N mice by intraperitoneal injection of isoproterenol

摘要:

目的 探索腹腔注射异丙肾上腺素（ISO）诱导FVB/N小鼠心脏重塑的可行性。方法 根据ISO不同的给药途径将48只FVB/N小鼠分为背部皮下盐水组（皮下盐水组）、腹腔盐水组、背部皮下ISO组（皮下ISO组）、腹腔ISO组（n=12）。皮下ISO组和腹腔ISO组小鼠每日均给予ISO（30 μg/g体重），分2次注射，间隔12 h，共14 d；两对照组按照不同给药途径注射等量生理盐水。超声心动图检测小鼠舒张末期左心室后壁厚度（dLVPW）；测量心胫比；苏木精-伊红染色测量心肌纤维直径；苦味酸-天狼猩红染色法检测心肌胶原沉积面积；荧光定量PCR测定Ⅰ型胶原（CollagenⅠ）mRNA表达水平。结果 与皮下ISO组、皮下盐水组和腹腔盐水组比较，腹腔ISO组小鼠心腔和心脏大体形态增大；与皮下盐水组和腹腔盐水组比较，皮下ISO组小鼠心腔和心脏大体形态无明显变化。腹腔ISO组小鼠心胫比、心肌纤维直径、dLVPW、心脏胶原面积百分比和CollagenⅠmRNA水平均明显高于皮下ISO组、皮下盐水组和腹腔盐水组（P < 0.01）；皮下ISO组小鼠上述指标与皮下盐水组和腹腔盐水组比较，差异均无统计学意义（P > 0.05）。两种途径给予小鼠注射ISO死亡率比较差异无统计学意义（P > 0.05）。结论 腹腔注射ISO可诱导出FVB/N小鼠心脏肥大和纤维化模型。

Abstract:

Objective To explore the feasibility of intraperitoneal injection of isoproterenol (ISO) to induce cardiac remodeling in FVB/N mice. Methods Forty-eight FVB/N mice were divided into back subcutaneous saline group (subcutaneous saline group), intraperitoneal saline group, back subcutaneous ISO group (subcutaneous ISO group), and intraperitoneal ISO group according to the route of administration of saline or ISO. ISO (30 μg/g body weight/day) was given to the subcutaneous ISO group and the intraperitoneal ISO group, twice daily with an interval of 12 hours, for 14 consecutive days. The subcutaneous saline group and the intraperitoneal saline group were injected with an equal volume of saline. The left ventricular end-diastolic posterior wall thickness was measured by echocardiography, and the ratio of heart weight to tibia length was determined. Hematoxylin-eosin staining was used to determine the myocardial fiber diameter. Picric-sirius red staining was used to determine the myocardial collagen deposition area. Quantitative real-time PCR was used to measure the mRNA expression of collagen I. Results Compared with the subcutaneous ISO, subcutaneous saline, and intraperitoneal saline groups, the intraperitoneal ISO group had increased sizes of the cardiac cavity and the heart. Compared with the subcutaneous saline and intraperitoneal saline groups, the subcutaneous ISO group showed no significant changes in the gross morphology of the cardiac cavity and the heart. The intraperitoneal ISO group showed significant increases in the ratio of heart weight to tibia length, myocardial fiber diameter, left ventricular end-diastolic posterior wall thickness, myocardial collagen area percentage, and the mRNA expression of collagen I compared with the subcutaneous ISO, subcutaneous saline, and intraperitoneal saline groups (P < 0.01). There were no significant differences in the above five indices between the subcutaneous ISO group and the subcutaneous saline and intraperitoneal saline groups (P > 0.05). No significant difference in the mortality rate was found between the subcutaneous ISO and intraperitoneal ISO groups (P > 0.05). Conclusions Intraperitoneal injection of ISO can induce cardiac hypertrophy and fibrosis in FVB/N mice.