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甲状腺功能亢进大鼠比目鱼肌肌浆网Ca~(2+)--ATP酶活性增高可加速强直收缩疲劳

余志斌, 焦博, 王云英, 李辉

第四军医大学航空航天医学教育部重点实验,室航空航天生理学教研室.陕西,西安 710032

摘要

甲状腺功能亢进(甲亢)时甲状腺素分泌增加，不仅使具有神经支配的慢缩型肌纤维向快缩型转化，而且改变骨骼肌的强直收缩功能。因此，甲亢性肌病的肌肉乏力可能与骨骼肌强直收缩易发生疲劳有关。该实验在离体条件下，观测甲亢4周引起的大鼠慢缩肌-----比目鱼肌(soleus, SOL)单收缩与间断强直收缩功能的变化。结果表明，甲亢4周大鼠(T4)体重明显低于同步对照组[(292±13) g vs (354±10) g]，但SOL湿重没有明显改变[(107.3±8.6) mg vs (115.1±6.9) mg]。甲亢大鼠SOL单收缩张力达到峰值的时间(time to peak tension, TPT)与从峰值降至75%舒张时间(time from peak tension to 75% relaxation, TR_(75))均明显缩短；强直收缩的TR_(75)也明显缩短[(102.8±4.1) ms vs (178.8±15.8) ms]；强直收缩的最适频率从对照组的100 Hz增加到140 Hz；间断强直收缩期间容易发生疲劳。甲亢大鼠SOL肌浆网Ca~(2+)--ATP酶(sarcoplasmic reticulum Ca~(2+)--ATPase, SERCA)活性增高。采用肌浆网特异性抑制剂CPA (1.0 #mu#mol/L)处理后，对照与甲亢大鼠SOL间断强直收缩的TR_(75)均延长，同时不易出现疲劳。5.0 #mu#mol/L CPA灌流虽可进一步抵抗甲亢大鼠SOL间断强直收缩引起的疲劳，但强直收缩期间的静息张力却明显升高。将CPA浓度增至10.0 #mu#mol/L，甲亢大鼠SOL间断强直收缩又趋向易发生疲劳。这些结果提示，与心肌相同，骨骼肌肌纤维SERCA活性亦可影响单收缩与强直收缩的舒张时间，SERCA活性升高可能加速间断强直收缩发生疲劳。

关键词： 甲状腺素; 比目鱼肌; 疲劳; 肌浆网Ca~(2+)-ATP酶

Increased activity of sarcoplasmic reticulum Ca~(2+)--ATPase in soleus of hyperthyroid rat accelerates fatigue during intermittent tetanic contraction

Yu Zhibin, Jiao Bo, Wang Yunying, Li Hui

Key Laboratory of Aerospace Medicine,Ministry of Education,Department of Aerospace Physiology,the Fourth Military Medical University.Xi'an 710032,Shaanxi

Abstract

The elevated plasma levels of thyroxin and/or triiodothyronine in hyperthyroidism not only induces a transition from the innervated slow-twitch muscle fibers to fast-twitch fibers, but also changes the contractile function in transited muscle fibers. So the muscle weakness of thyrotoxic myopathy would relate to alteration in fatigability of tetanic contract in muscles, especially in slow-twitch fibers. The aim of the present study was to observe the extent of fatigue of soleus in 4-week hyperthyroid rats and elucidate its underlying mechanism. The isolated soleus muscle strips were perfused in Krebs-Henseleit solution with or without an inhibitor of sarcoplasmic reticulum Ca~(2+)-ATPase (SERCA), cyclopiazonic acid (CPA). The contractile function of soleus was observed in twitch and intermittent tetanic contraction. The body weight in 4-week hyperthyroid rats decreased as compared with that in the control group [(292±13) g vs (354±10) g], but there was no difference between hyperthyroid and control groups in the wet weight of soleus [(107.3±8.6) mg vs (115.1±6.9) mg]. The time to peak tension (TPT) and time from peak tension to 75% relaxation (TR_(75)) in twitch contraction were shortened in the soleus of hyperthyroid rat, the TR_(75) of tetanic contraction was also shortened as compared with that in the control group [(102.8±4.1) ms vs (178.8±15.8) ms]. The optimal stimulation frequency at which a maximal tension of tetanic contraction happened was shifted from 100 Hz in the control group to 140 Hz in hyperthyroid group. The soleus of hyperthyroid rat was easier to fatigue than that of the control rat during intermittent tetanic contraction. The SERCA activity also increased in soleus of hyperthyroid rat. The TR_(75) in tetanic contraction was prolonged and showed an increased fatigue resistance in the soleus of control and hyperthyroid groups with 1.0 #mu#mol/L of CPA perfusion. The fatigue resistance of tetanic contraction in the soleus of hyperthyroid rat increased further with 5.0 #mu#mol/L of CPA treatment, but the resting tension kept rising. 10 #mu#mol/L of CPA reduced the fatigue resistance of tetanic contraction in the soleus of hyperthyroid rat. The above results demonstrate that the SERCA activity in soleus can also influence the relaxation duration of twitch contraction like that in the myocardium. The SERCA activity in slow-twitch fibers is possibly involved in the regulation of fatigue resistance of intermittent tetanic contraction.

Key words: thyroid;soleus;Fatigue;sarcoplasmic reticulum Ca~(2+)-ATPase

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引用本文：

余志斌, 焦博, 王云英, 李辉. 甲状腺功能亢进大鼠比目鱼肌肌浆网Ca~(2+)--ATP酶活性增高可加速强直收缩疲劳[J]. 生理学报 2008; 60 (3): 362-368.

Yu Zhibin, Jiao Bo, Wang Yunying, Li Hui. Increased activity of sarcoplasmic reticulum Ca~(2+)--ATPase in soleus of hyperthyroid rat accelerates fatigue during intermittent tetanic contraction. Acta Physiol Sin 2008; 60 (3): 362-368 (in Chinese with English abstract).