| 摘要: |
| 目的探讨心肌细胞自噬在仔鼠围生期甲状腺功能减退（简称甲减）致心功能损害中的作用，并观察左旋甲状腺素（L-T4）替代治疗后自噬指标的改变。方法SD孕鼠自孕15d起每日予丙基硫氧嘧啶（PTU）50mg/d灌胃至仔鼠出生并持续整个哺乳期，制成围生期甲减模型，出生仔鼠为甲减组，其余孕鼠每日予0.9%氯化钠溶液灌胃，出生仔鼠为对照组，部分甲减仔鼠自出生当日起予以每日腹腔注射L-T42μg/100g，为治疗组，收集甲减组、治疗组及对照组（每组8只）出生7d龄仔鼠的心室肌组织，采用Westernblot法测定并比较心肌组织自噬相关蛋白LC3与cathepsinD的表达，同时测定并比较血清甲状腺激素水平及CK-MB、LDH与AST水平。结果甲减组仔鼠CK-MB、LDH及AST水平均高于对照组（均P＜0.01），治疗组仔鼠3者水平均较甲减组下降（均P＜0.01）；甲减组仔鼠LC3II/LC3I及cathepsinD表达水平均高于对照组（均P＜0.01），治疗组仔鼠2者的表达水平均较甲减组降低（均P＜0.01）。结论心肌细胞自噬在围生期甲减诱发新生仔鼠心功能损害中起重要作用。 |
| 关键词: 甲状腺功能减退症 自噬 微管相关蛋白 LC3 新生大鼠 |
| DOI： |
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| 基金项目:浙江省教育厅科研项目；浙江省人口计划生育科研项目 |
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| Alteration of cardiomyocyte autophagy in neonatal hypothyroid rats |
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MAO Shanshan, SHEN Jue, QIU Yunxiang
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the Children Hospital of Zhejiang University School of Medicine
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| Abstract: |
| Objective To investigate the alteration of cardiomyocyte autophagy in neonatal hypothyroid rats. Methods Hypothyroidism was induced by gavage of propylthiouracil (PTU, 50mg/d) solution from embryonic d15 through the lactational period in pregnant SD rats. The offspring of hypothyroid rats was divided into two groups: in L-T4 treatment group (n=8) the neonatal rats received intraperitoneal injection of levothroxine (L-T4, 2 μg/100g.d) starting from the day of birth; in hypothyroid group(n=8) the neonatal rats received normal saline instead of L-T4. The offspring of normal pregnant rats served as control group (n=8). Animals were sacrificed at postnatal d7. Serum thyroid hormone levels and myocadial enzymes CK-MB, LDH and AST were measured; LC3I, LC3II and cathepsin D protein levels were detected by Western blotting. Results Hypothyroid neonatal rats had significant higher myocardial CK-MB, LDH and AST levels than those in control group (P＜0.01), while those indicators were significantly decreased in L-T4 treatment group compared to hypothyroid group. Compared with control group, LC3I, LC3II and
cathepsin D protein levels were significantly higher(P＜0.01) in neonatal hypothyroid group(P＜0.01), while L-T4 treatment group showed a significant decrease compared with hypothyroid group (P ＜0.01). Conclusion Cardiomyocyte autophagy may be involved in the pathogenesis of myocardial systolic and diastolic dysfunction in hypothyroidism neonatal rats. |
| Key words: Hypothyroidism Autophagy Microtubule-associated protein LC3 Neonatal rat |
