异丙肾上腺素诱导恒河猴心肌损伤模型的初步研究

Preliminary study of an isoproterenol-induced myocardial injury model in rhesus monkeys

目的应用异丙肾上腺素诱导恒河猴心肌损伤模型方法的初步探索。方法选用11只恒河猴分为高剂量组、低剂量组、对照组。模型组每次注射ISO剂量分别为4.6 mg/kg、3.2 mg/kg,每天2次;对照组注射生理盐水1 mL,每天1次。分别于注射后第1、3、5、7天及第2、3、4、5周进行彩色多普勒超声影像检查:左室舒张末期的室间隔厚度(IVSTd)、左室内径(LVEDD)、左室后壁厚度(LVPWTd),收缩末期的室间隔厚度(IVSTs)、左室内径(LVESD)、左室后壁厚度(LVPWTs)、及左心室短轴缩短率(FS)、射血分数(EF)、左心室质量(LVM);心电仪检查心电图变化;同时进行谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酸肌酶(CK)、肌酸肌酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、血小板/淋巴细胞比值(PLR)、中性粒细胞/淋巴细胞比值(NLR)等血液生理生化指标检测。结果高剂量组在给药1周内,AST、ALT、LDH、CK、CK-MB、PLR、NLR明显升高;IVSTd、IVSTs、LVPWTd、LVPWTs、LVEDD、LVESD增加,EF、FS降低。与高剂量组相比,低剂量组变化不明显。心电结果显示给药后至第5周持续出现T波、ST段不同程度的改变。结论皮下注射ISO可诱导恒河猴心肌损伤,心脏超声、心电图及血液学的综合指标可作为恒河猴无创心脏损伤模型的评价依据。

Objective To investigate the method of using isoproterenol(ISO)to induce myocardial injury in rhesus monkeys.Methods Eleven rhesus monkeys were selected and divided into a high-dose,low-dose and control group.The injections of ISO in the model groups were 4.6 mg/kg(high-dose)and 3.2 mg/kg(low-dose)and conducted twice per day.The control animals were injected with 1 mL of normal saline once per day.Color Doppler ultrasound imaging examinations were performed on days 1,3,5,7 and weeks 2,3,4,and 5 after the injections and included:IVSTd,IVSTs,LVPWTd,LVPWTs,LVEDD,LVESD,EF,FS,LVM.Electrocardiography was used to measure the changes in cardiac electrical activity.AST,ALT,LDH,CK,CK-MB,PLR,NLR and other physiological and biochemical indicators in the blood were measured. Results In the high-dose group, AST, ALT, LDH, CK, CK-MB, PLR and NLR increased significantly within one week of ISO administration. Furthermore, IVSTd, IVSTs, LVPWTd, LVPWTs, LVEDD and LVESD increased, EF and FS decreased. Compared with that in the high-dose group, these values in the low-dose group were similar to the control group. The electrocardiography result showed that the T wave and ST segments changed to varying degrees by the fifth week after ISO administration. Conclusions Subcutaneous injection of ISO can induce myocardial injury in rhesus monkeys. These comprehensive indices of echocardiography, electrocardiography, and hematology can be used as the basis for evaluating non-invasive heart injury in rhesus monkeys.