小剂量异丙肾上腺素致大鼠心衰伴甲状腺功能紊乱动物模型

Heart Failure Model with Thyroid Dysfunction Induced by Low-dose Isoprenaline

目的探索采用小剂量异丙肾上腺素（ISO）制备心衰伴低T3综合征的大鼠模型。方法根据ISO给药剂量及给药方式将大鼠随机分为6组，另设对照组注射2ml生理盐水。于给药前和给药后10d各行心脏超声心动图检查，检测血清游离三碘甲状腺原氨酸、游离甲状腺素、肌酸激酶、乳酸脱氢酶（FT3、FT4、CK、LDH）浓度。给药后11d处死动物取心脏做氯化三苯基四氮唑（TTC）染色。结果（1）各组动物存活率，3mg·kg-1.d-1组全部存活，5mg·kg扎d。x3d组、10mg·kg-1d-1×3d组、6mg·kg-1d-1×7d组存活率分别为50％、60％、80％；（2）与对照组相比，各组左室短轴缩短率（Fs）均明显降低（P〈0．01），且6组较其他组下降明显（P〈0．05）；（3）CK、LDH较给药前显著升高（P〈0．05），6mg.kg-1.d-1×7d组血清FT3浓度明显低10mg.kg-1d-1×3d组（P〈0．05）；（4）与对照组相比，实验组心梗面积明显（P〈0．05），6mg·kgLd。×7d组心肌梗死重量百分比明显高于10mg.kg-1d-1×3d组（P=0．02）。结论（6mg·kg-1d-1）ISO分2次腹腔注射，给药间隔1h，连续给药7d，可成功制备心衰伴甲状腺功能紊乱动物模型，该方法操作简便，重复性、可控性、稳定性好，死亡率低、成功率高。

Objective To establish the rat experimental model of heart failure with thyroid dysfunc- tion by using low-dose Isoprenaline（ISO）. Methods In accordance with the dosage and route of administration of ISO, the rats were randomly divided into 6 experiment groups and the control group with 2 ml saline by intraperitoneal injection.Before administration and on 10 day after administration, echocardiography was conducted and CK, LDH, FT3, FT4 were detected. On 11 day the animals were sacrificed and the hearts were sampled for TTC staining. Results （1）No death in group 3mg.kg-kd-1,the survival rate in group 5 mg.kg-1.d-1x3 d-1 0 kg-1.d-1x3 d and 6 mg.kg-1.d-1x7d were 50%, 60%, 80% respectively; （2） compared with the control group,left ventricular fractional shortening （FS） was significantly decreased in all groups （P〈0.05）, and group 6 mg.kg-1.d-1x7 d was lower than the others（P〈0.05）; （3） CK and LDH increased more significantly after administration, and serum FT3 concentration in group 6 mg.kg-1.d-1x7 d obviously lower than group 10 mg.kg-1.d-1x3 d （P〈0.05）; （4） the myocardial infarction area in experimental group was more obvious compared with the control group（P〈0.05）, the percentage of the myocardial infarction weight was more visible in group 6 mg.kg-1.d-1x7 d compared with group 10 mg.kg-1.d-1x3d （P=0.02）. Coneulusion The best dosage and route of administration was that administering ISO （6 mg.kg-1.d-1） by intraperitoneal injection, the total dose was done twice with one hour interval,continuous administration for 7 days. This experiment provided an easy way to establish the animal model of heart failure with thyroid dysfunction, which was reproducible,credibie, stable and had low mortality and a high success rate.