Changes in Acetylcholine Receptors and Functional Characterization in Muscle by TOF Stimulation in Rat Experimental Autoimmune Myasthenia Gravis (EAMG) Model / 대한마취과학회지

ABSTRACT

BACKGROUND: The aim of study is to investigate the initial functional changes of muscle in rats induced to have myasthenia gravis, experimental autoimmune myasthenia gravis (EAMG). The authors investigated the functional changes of muscle evaluated by mechanomyography (MMG) and the expression of acetylcholine receptors (AChRs). METHODS: After the institutional approval, 39 male Lewis rats were randomly allocated into study. 26 animals were immunized to induce EAMG by Torpedo AChR (T-AChR) emulsified with complete Freund's adjuvant (CFA) and phosphate buffer saline (PBS)/bovine serum albumin (BSA) 0.01% at the base of tail, and received booster immunizations twice by T-AChR with incomplete Freund's adjuvant (IFA) and PBS/BSA 0.01% at all different site on the upper back. 13 animals were sham immunized as control group by the same method of EAMG except T-AChR. Clinical EAMG scores were examined. Anti T-AChR and anti rat-AChR (R-AChR) antibodies (Ab) were compared by using (125)I-alpha-bungarotoxin ((125)I-alpha-BuTx) radioimmunoassay. Under the anesthesia, neuromuscular functions were monitored by MMG using single twitch (ST) and TOF. AChRs were quantitated using (125)I-alpha-BuTx. RESULTS: Overall weight gain and final body mass, muscle force (ST), specific muscle force of ST, TOF fade ratio and AChRs were reduced in EAMG score 3 compared to control (P < 0.0001). Anti T-AChR Ab and anti R-AChR Ab were increased in score 3 EAMG (P < 0.0001). CONCLUSIONS: EAMG score 3 rats showed characteristic neuromuscular functions as depressed initial ST and its specific force, initial TOF fade and increased anti AChR Abs. Those above characteristics had significant correlations with the clinical EAMG scores. AChRs were significantly down-regulated according to their functional characteristics and clinical EAMG scores.