Decreased collagen mRNA and regression of cardiac fibrosis in the ventricular myocardium of the tight skin mouse following thyroid hormone treatment.
Decreased collagen mRNA and regression of cardiac fibrosis in the ventricular myocardium of the tight skin mouse following thyroid hormone treatment.
复制标题
甲状腺激素治疗后紧皮小鼠心室心肌中胶原蛋白 mRNA 减少和心脏纤维化消退。
DOI：
10.1093/cvr/26.6.603
复制
发表时间：
1992
影响因子：
10.8
通讯作者：
Eghbali,M
中科院分区：
文献类型：
--
作者：
Yao,J;Eghbali,M
目的：研究甲状腺激素对心肌纤维化遗传模型TSK（tightskinmouse）心肌胶原基因表达的影响。方法：选用1.5 ~ 2月龄C57 BL/6品系雄性TSK/+（n= 20）和正常（+/+）纯合子小鼠（n=20）。通过测量心脏重量/体重比和组织学变化，检查甲状腺激素治疗（L-甲状腺素，每日腹腔注射10 μg·100 g-1体重）后的心室肥大。通过测量其各自mRNA的丰度来检查心室肌中纤维胶原I型和III型的表达。胶原合成通过测量羟脯氨酸来检查。通过免疫荧光染色评价胶原类型的沉积。非胶原蛋白，肌节和细胞骨架肌动蛋白的表达，测定在mRNA水平。结果：治疗12天后，心室肥大诱导的TSK小鼠的心脏。北方杂交结果表明，TSK小鼠心脏中前α2（I）型胶原mRNA的丰度在甲状腺素处理后24 h下降了32与未治疗的TSK小鼠相比，前α1（III）胶原蛋白减少47%（p<0.002），细胞骨架肌动蛋白减少50%（p<0.005），肌节肌动蛋白mRNA减少34%（p<0.01）。甲状腺素处理的TSK小鼠中前α2（I）和前α1（III）胶原的mRNA丰度与正常纯合子小鼠几乎相当。TSK小鼠治疗12 d后，心肌胶原含量较正常纯合子小鼠降低22.5%（p<0.01）。结论：甲状腺激素对TSK小鼠心室基因表达的影响导致胶原mRNA和胶原含量减少，心肌纤维化消失。甲状腺激素可能通过内分泌途径选择性地阻止心脏纤维化的发生，并在心脏纤维化的消退中发挥重要作用。
Objective:The aim was to study the effect of thyroid hormone on collagen gene expression in the myocardium of the tight skin mouse (TSK), a genetic model of myocardial fibrosis.Methods:Heterozygous male (TSK/+) (n=20) and normal (+/+) homozygous mice (n=20), 1.5-2 months old of the C57BL/6 strain were studied. Ventricular hypertrophy following thyroid hormone treatment (L-thyroxine, 10 μg·100 g−1body weight daily intraperitoneally) was examined by measurement of the heart weight/body weight ratios and histological changes. Expression of fibrillar collagen types I and III in the ventricular myocardium was examined by measurement of the abundance of their respective mRNAs. Collagen synthesis was examined by measurement of hydroxyproline. Deposition of collagen types was evaluated by immunofluorescence staining. Expression of non-collagenous proteins, sarcomeric and cytoskeletal actin, was measured at the mRNA level.Results:After 12 days of treatment ventricular hypertrophy was induced in the heart of the TSK mice. The results of northern hybridisation analyses showed that in the hearts of TSK mice 24 h after thyroxine treatment the abundance of mRNA for pro α2(I) collagen was decreased by 32% (p<0.05), pro α1(III) collagen by 47% (p<0.002), cytoskeletal actin by 50% (p<0.005), and sarcomeric actin mRNA by 34% (p<0.01) compared to the untreated TSK mice. The abundance of mRNA for pro α2(I) and pro α1(III) collagens in the thyroxine treated TSK mice were nearly comparable to that in normal homozygous mice. In TSK mice which were treated for 12 d, collagen content of the ventricular myocardium, as determined by hydroxyproline measurements, was decreased by 22.5% (p<0.01) compared to that in the heart of normal homozygous mice.Conclusions:Effects of thyroid hormone on ventricular gene expression in TSK mice result in a diminished collagen mRNA and collagen content and the disappearance of cardiac fibrosis. Thyroid hormone may selectively prevent the induction of cardiac fibrosis and play an important role in regression of cardiac fibrosis via endocrine pathways.