摘要
目的建立Lewis大鼠肌肉特异性激酶（MuSK）的实验性自身免疫性重症肌无力模型（EAMG）。方法以小鼠MuSK基因编码序列为模板合成小鼠MuSK抗原。以Lewis大鼠为实验动物，采取主动免疫方法将免疫原小鼠MuSK与弗氏完全佐剂混合制成抗原乳剂，免疫注射部位为大鼠尾根部皮下，抗原剂量分别为50μg和100μg，对照组大鼠仅免疫弗氏完全佐剂。免疫后隔日记录3组的临床评分，以酶联免疫吸附法（ELISA）检测免疫后第7天及第57天大鼠血清中MuSK抗体滴度。结果大鼠于免疫后第16天发病，第18—22天达到发病高峰。50μg实验组发病大鼠百分率为71．4％，100μg实验组发病大鼠百分率为100％，实验组总发病大鼠百分率为80％。第7天及第57天大鼠血清中，ELISA法检测显示实验组MuSK—Ab滴度显著高于对照组（P〈0．05）。结论以上方法可成功诱导出MuSK特异性EAMG模型。该模型有助于揭示人类MuSK抗体阳性重症肌无力（AMM）的发病机制，并可为临床药物治疗提供实验学依据。
Objective To establish the experimental autoimmune Lewis rat model of myasthenia gravis （EAMG） specific for muscle-specific kinase （MUSK）. Methods Lewis rats were immunized subcutaneously with a single injection of 200μl of MuSK （50/100 μg） emulsified in complete Freund＇s adjuvant （CFA）. And MuSK was expressed according to the murine gene of MuSK （AY360453）. Control rats were immunized with CFA alone. All rats were observed every other day in a blinded fashion for fatigue characteristics. The clinical symptoms were graded between 0 and 3. And the clinical scores were recorded. The serum levels of anti-MuSK IgG at Days 7 and 57 were determined by enzyme-linked immunosorbent assay （ELISA）. Results The clinical symptoms of myasthenia garvis （MG） appeared at Day 16 and peaked at Days 18 - 22. The serum levels of anti-MuSK IgG were markedly elevated in the experimental groups compared with the control group. Conclusion EAMG induced by MuSK is successfully established in rats. And this animal model may help us elucidate the pathogenesis of anti-MuSK myasthenia （AMM） and discover new drug therapy in the future.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2013年第17期1292-1296,共5页
National Medical Journal of China
基金
北京市科技新星计划（20088069）
