摘要
目的:改进现有呋喃唑酮(Fz)诱导SD大鼠扩张型心肌病(DCM)动物模型,使其血生化、心功能及组织病理改变更接近人类DCM临床病理生理过程。方法:150只2周龄SD大鼠分为四组,分别按Fz 0.30 mg/g、0.25 mg/g、0.20 mg/g灌胃,每日1次,以生理盐水为对照,分别在给药4、8、12和16周检查大鼠一般状况,检验血清肌钙蛋白I、肌钙蛋白T和N端前体脑钠肽水平,心脏功能和电镜、光镜观察组织病理改变。结果:(1)实验组鼠生长状况差,逐渐出现肢体水肿,站立行走不稳等症状,高、中、低剂量组大鼠各时间点体重明显小于相应对照组,而心脏重量/体重比值却高于相应对照组;(2)实验组大鼠给药8、12、16周超声检测发现心腔扩大,左室后壁动度明显减弱,部分出现同向运动;(3)高、中、低剂量组鼠各时间点右心房压均明显高于相应对照组鼠,心率较相应对照组鼠慢,主动脉压无明显差异;(4)实验组鼠给药8、12、16周HE染色显示心肌出现心肌纤维肥大、非特异性退行性变及间质纤维化,肝和肺有明显淤血;(5)实验组鼠给药8、12、16周苦味酸-天狼星红偏振光法观察心肌纤维化随年龄增长而逐渐加重,各型胶原比例失调,排列紊乱;(6)实验组鼠给药8、12、16周电镜显示心肌线粒体增生肿胀,肌丝排列紊乱,心肌细胞肥大和萎缩同时存在,有变性、坏死及纤维化。结论:中剂量Fz(0.25mg/g)灌胃12周作为大鼠DCM模型在临床表现,病理生理上与人类DCM更相似。
Objective： To improve the current SD rat dilated cardiomyopathy（DCM） animal model induced by furazolidone（Fz）,and make the serum biochemistry test,histopathology and cardiac function examination results be closer to human clinical pathophisiology.Methods： Sixty 2-week-old SD rats were divided into four groups,and administered by gavage daily with Fz 0.20 mg/g,0.25 mg/g,and 0.30 mg/g respectively.On the given time points of 4,8,12 and 14 week,DCM related data were collected,which included physical examination,serum cTnI,cTnT and NT-proBNP levels,cardiac function by ultrasonic Doppler and histopathological examination by electron and optical microscopes.Results： The rats in the experimental group grew poorly and gradually emerged limb edema,unsteady standing,abnormal gait and other symptoms.And compared with the rats in the control group,its body weights were lower,while its ratios of heart weight and body weight were significantly higher.On the time points of 8,12 and 16 week,ultrasonic imaging detected expanding of cardiac chambers and weakening mobility of the left ventricular posterior walls sometimes even with codirectional movement in the rats of the experimental groups.On each time point,the right atrial pressure values of the rats in the experimental group were significantly higher and its heart rates were significantly fewer,but the aortic pressure differences were not significant.On the time points of 8,12 and 16 week,HE staining showed that the rats in the experimental group had myocardial hypertrophy,non-specific degeneration and interstitial fibrosis,as well as congestion in its livers and lungs.On the time points of 8,12 and 16 week,picric acid-Sirius red staining polarized optical observation showed gradually increased myocardial fibrosis,collagen type proportion imbalance and disorganization in experimental groups.On time points of 8,12 and 16 week,electron microscopy revealed myocardial mitochondria proliferation and swelling,myofilament derangement,the coexistent of cardiocytes hypertrophy and atrophy,and the degeneration,necrosis and fibrosis.Conclusion： The SD rat DCM animal model with Fz 0.25 mg/g administered by gavage daily for 12 weeks provides closer data compared with human DCM’s clinical pathophisiology
出处
《现代生物医学进展》
CAS
2013年第10期1829-1835,1819,共8页
Progress in Modern Biomedicine
基金
中青年内分泌医师科研基金(21460#)
陕西省科技社会发展攻关项目(2011K14-01-07)
关键词
扩张型心肌病
呋喃唑酮
心功能
组织病理
Dilated cardiomyopathy
Furazolidone
Cardiac function
Histopathologycal
