铁过载致心肌纤维化小型猪模型的建立

Establishment of a miniature pig model of myocardial fibrosis induced by iron overload

目的建立铁过载致心肌纤维化的小型猪模型,探讨铁过载致心肌纤维化的作用机制/病理生理特征。方法选取巴马小型猪18只,随机分为实验组15只、对照组3只。每隔7 d经肌内注射右旋糖酐铁溶液1次,首次剂量为400 mg/kg,其余剂量为200 mg/kg,对照组注射与实验组相同剂量生理盐水,于注射铁剂6 d后随机处死1~2只巴马小型猪;取部分心脏组织切片进行心肌胶原容积分数(CVF)测定和心肌铁半定量测定,剩余心脏组织用于测量心脏铁浓度(CIC)。结果随注射次数增多,实验组巴马猪CIC呈上升趋势,心肌胶原纤维及铁颗粒占视野面积比例增多。注射铁总量与CIC、心肌铁病理半定量、CVF之间高度正相关(r=0.957,r=0.971,r=0.957,P<0.001),CIC与CVF之间高度正相关(r=0.924,P<0.001),心肌铁半定量与CIC、CVF之间高度相关(r=0.973,P<0.001;r=0.944,P<0.001)。结论通过肌内注射首次剂量为400 mg/kg,后续剂量为200 mg/kg的右旋糖酐铁,共15次,可以建立心肌纤维化小型猪模型,心肌铁颗粒沉积越多提示心肌纤维化程度越严重。

Objective To establish an animal model of myocardial fibrosis induced by iron overload.Methods Eighteen Bama minipigs were randomly divided into an experimental group(n=15)or control group(n=3).An iron dextran solution was intramuscularly injected every seven days.The first dose was 400 mg/kg,and the other doses were 200 mg/kg.The control group was injected with the same volume of normal saline.One to two Bama minipigs were randomly euthanized 6 days after injection of iron.Cardiac tissue sections were used for myocardial collagen volume fraction(CVF),semiquantitative myocardial iron,cardiac iron concentration(CIC)measurements.Results With the increase in the number of injections,CIC in the experimental group showed an upward trend,and the proportions of myocardial collagen fibers and iron particles were increased.The total amount of injected iron was highly correlated to CIC,myocardial iron,and CVF(r=0.957,r=0.971,r=0.957,P<0.001).CIC was highly correlated to CVF(r=0.924,P<0.001),and myocardial iron was highly correlated to CIC and CVF(r=0.973,P<0.001;r=0.944,P<0.001).Conclusions A miniature pig model of myocardial fibrosis was established by intramuscular injection of 400 mg/kg iron dextran as the first dose and 200 mg/kg iron dextran as the other doses.More iron particles deposited in the myocardium led to more severe myocardial fibrosis.