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甲状腺素诱导心肌肥厚过程中的乙酰胆碱水平、胆碱乙酰转移酶和乙酰胆碱酯酶分子形式

Acetylcholine levels, choline acetyltransferase and acetylcholinesterase molecular forms during thyroxine-induced cardiac hypertrophy.

作者信息

Nyquist-Battie C, Hagler K E, Windberg L, Thottassery J V

机构信息

School of Basic Life Sciences, University of Missouri, Kansas City 64108.

出版信息

Neurochem Int. 1993 Feb;22(2):143-51. doi: 10.1016/0197-0186(93)90007-r.

DOI:10.1016/0197-0186(93)90007-r
PMID:8439768
Abstract

The effects of left ventricular hypertrophy induced by hyperthyroidism on three biochemical markers of parasympathetic innervation were investigated. In response to subcutaneous injections of thyroxine (400 micrograms/kg; T4) for 6 days, the left ventricle, but not the right, developed significant hypertrophy (20%). In the enlarged left ventricle, acetylcholine (ACh) content and choline acetyltransferase (ChAT) activity per chamber were elevated approx. 25-30%, although no change in these two markers was evident when the data were expressed per unit wet weight. Immunoblot analysis showed that the relative abundance of ChAT protein increased in the hypertrophied left ventricle in correlation with the increased ChAT activity. No changes in ACh content, ChAT activity and ChAT relative abundance were evident in the right ventricle of T4-treated animals. Although hyperthyroidism did not alter AChE specific activity (per unit wet weight) in the left ventricle, the percent activities of the individual AChE globular forms were affected in this chamber. Specifically, T4-treatment reduced the percent activity of globular (G)4 AChE by 20% and increased that of the combined G1 and G2 AChE pool by 15%. Interestingly, in the hypertrophied left ventricle total AChE activity in its extracellular or functionally-relevant pool was reduced due to a loss of G4 AChE activity. These results show that a compensatory increase in parasympathetic innervation can occur during hyperthyroid-induced left ventricular hypertrophy. However, the reduced activity of the functionally-relevant AChE pool suggests that the clearance of ACh after release may be slowed in the hypertrophied left ventricle.

摘要

研究了甲状腺功能亢进诱导的左心室肥厚对副交感神经支配的三种生化标志物的影响。皮下注射甲状腺素(400微克/千克;T4)6天后,左心室而非右心室出现显著肥厚(20%)。在扩大的左心室中,每个腔室的乙酰胆碱(ACh)含量和胆碱乙酰转移酶(ChAT)活性大约升高了25 - 30%,尽管以单位湿重表示数据时这两种标志物没有明显变化。免疫印迹分析表明,ChAT蛋白的相对丰度在肥厚的左心室中增加,与ChAT活性增加相关。在接受T4治疗的动物的右心室中,ACh含量、ChAT活性和ChAT相对丰度没有明显变化。虽然甲状腺功能亢进没有改变左心室中乙酰胆碱酯酶(AChE)的比活性(每单位湿重),但该腔室中各个AChE球状形式的活性百分比受到影响。具体而言,T4治疗使球状(G)4 AChE的活性百分比降低了20%,并使G1和G2 AChE组合池的活性百分比增加了15%。有趣的是,在肥厚的左心室中,由于G4 AChE活性丧失,其细胞外或功能相关池中的总AChE活性降低。这些结果表明,在甲状腺功能亢进诱导的左心室肥厚期间,副交感神经支配可发生代偿性增加。然而,功能相关的AChE池活性降低表明,在肥厚的左心室中,ACh释放后的清除可能会减慢。

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