Tsukagoshi H, Morita T, Takahashi K, Kunimoto F, Goto F
Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Gunma-Ken, Japan.
Anesthesiology. 1999 Aug;91(2):448-60. doi: 10.1097/00000542-199908000-00020.
Although systemic inflammation is believed to cause upregulation of nicotinic acetylcholine receptors (nAchRs) in muscle, chronic infections such as Chagas' disease occasionally are complicated by myasthenia gravis. The authors investigated how a nonlethal cecal ligation and puncture (CLP) peritonitis model in rats could affect muscle nAchR.
On day 1, 4, 7, 14, or 21 after CLP or sham operation, nAchR binding was assayed in the anterior tibial muscle and diaphragm using [125I]alpha-bungarotoxin. The presence or absence of weakness, in vivo dose-response relationships for d-tubocurarine, and serum anti-nAchR antibody titers were assayed in separate experiments.
Systemic inflammation was most severe during the first 4 to 5 days. Numbers of nAchRs were decreased in anterior tibial muscle on days 7, 14, and 21 after CLP, and in the diaphragm on days 7 and 14 (P < 0.01). Both 50% and 90% blocking doses of d-tubocurarine) were lower in CLP rats than in sham-operated rats on days 7, 14, and 21 (P < .05). Weakness was overt in approximately half of CLP rats at these times. Serum anti-nAchR antibody (0.7-1.4 nM) was detectable beginning on day 4 and continuing throughout the 21-day observation period in 58-67% of CLP rats.
During the recovery phase of injury, nonlethal CLP peritonitis resulted in downregulation of nAchR. However, further study is needed to determine the role of anti-nAchR antibodies in the development of decreased receptor numbers and impaired neuromuscular function.
尽管全身炎症被认为会导致肌肉中烟碱型乙酰胆碱受体（nAchRs）上调，但恰加斯病等慢性感染偶尔会并发重症肌无力。作者研究了大鼠非致死性盲肠结扎和穿刺（CLP）腹膜炎模型如何影响肌肉nAchR。
在CLP或假手术后第1、4、7、14或21天，使用[125I]α-银环蛇毒素检测胫前肌和膈肌中的nAchR结合情况。在单独的实验中检测是否存在肌无力、d-筒箭毒碱的体内剂量反应关系以及血清抗nAchR抗体滴度。
全身炎症在最初4至5天最为严重。CLP后第7、14和21天，胫前肌中的nAchR数量减少，第7和14天膈肌中的nAchR数量减少（P<0.01）。在第7、14和21天，CLP大鼠的d-筒箭毒碱50%和90%阻断剂量均低于假手术大鼠（P<.05）。此时约一半的CLP大鼠出现明显肌无力。在58-67%的CLP大鼠中，从第4天开始可检测到血清抗nAchR抗体（0.7-1.4 nM），并在整个21天观察期持续存在。
在损伤恢复期，非致死性CLP腹膜炎导致nAchR下调。然而，需要进一步研究以确定抗nAchR抗体在受体数量减少和神经肌肉功能受损发展中的作用。
