摘要
目的:探索皮下注射免疫球蛋白(SCIg)对实验性自身免疫性重症肌无力(EAMG)小鼠的疗效。方法:采用皮下多点注射鼠源性AChR-α亚基97~116肽段主动免疫C57BL/6雌性小鼠,成功构建EAMG模型小鼠18只,随机分为EAMG组4只、泼尼松组4只、SCIg低剂量组5只、SCIg高剂量组5只。另取5只未造模的小鼠为正常组。正常组及EAMG组给予生理盐水0.2 mL/d灌胃,泼尼松组给予泼尼松9 mg/(kg·d)灌胃,共灌胃2周。SCIg低剂量组:每周2次皮下多点注射IgG,两周剂量均为2.25 mg/g;SCIg高剂量组:每周2次皮下多点注射IgG,第1、2周剂量分别为2.25、4.50 mg/g。第1次加强免疫后每隔1周测肌力,进行Lennon评分。治疗前、治疗2周后采血测血清AChR-Ab水平和IgG含量(ELISA法)。治疗2周后全自动血细胞分析仪测定白细胞计数(WBC)、嗜中性粒细胞计数(NEUT)和淋巴细胞计数(LYMPH),计算嗜中性粒细胞和淋巴细胞比值(NLR);取腓肠肌行电镜观察。结果:SCIg组治疗后血清AChR-Ab水平和Lennon评分均较治疗前降低(P<0.05),SCIg高剂量组降低程度大于低剂量组(P<0.05)。与EAMG组相比,SCIg高剂量组血清IgG含量、NEUT及NLR均降低(P<0.05)。EAMG组骨骼肌肌纤维间隙相对增宽,肌丝紊乱,线粒体数量明显减少,出现云絮状病变及空泡化;SCIg低剂量组肌纤维结构较清晰完整;SCIg高剂量组线粒体嵴致密度相对均匀,结构较为清晰,排列较规律。结论:皮下注射SCIg能够有效缓解EAMG小鼠的肌无力症状。
Aim:To investigate the therapeutic effects of subcutaneous injection of immunoglobulin(SCIg)on experimental autoimmune myasthenia gravis(EAMG)mice.Methods:C57BL/6 female mice were immuned actively by subcutaneous multipoint injection with rat-sourced AChR alpha subunit 97-116 peptide segments,to build EAMG model,and 18 were successfully constructed.The 18 EAMG mice were randomly allocated into EAMG group(n=4),prednisone group(n=4),low-dose SCIg group(n=5)and high-dose SCIg group(n=5).Another 5 unmodeled mice were taken as normal group.Normal group and EAMG group were given 0.2 mL/d of normal saline,prednisone group was given 9 mg/(kg·d)of prednisone for 2 weeks.In the low-dose SCIg group,IgG was given by multipoint subcutaneous injection,twice a week at a dose of 2.25 mg/g for two weeks.In the high-dose SCIg group,IgG was injected subcutaneously twice a week at a dose of 2.25 mg/g for the first week and 4.50 mg/g for the second week.Lennon score was performed every 2 weeks after the first booster.Serum AChR-Ab level and IgG content were measured before treatment and 2 weeks after treatment using ELISA method.White blood cell count(WBC),neutrophil count(NEUT),lymphocyte count(LYMPH),neutrophil to lymphocyte ratio(NLR)were measured by automatic blood cell analyzer,and gastrocnemius muscle was taken for electron microscopic observation 2 weeks after treatment.Results:Serum AChR-Ab level and Lennon score in the two SCIg groups were lower than those before treatment(P<0.05),and the decrease in the high-dose group was greater than that in the low-dose group(P<0.05).Compared with the EAMG group,the high-dose SCIg group had lower IgG content,lower NEUT,and lower NLR(P<0.05).In EAMG group,the gap of skeletal muscle fibers was relatively widened,the myofilament was disorganized,the number of mitochondria reduced,clouding and vacuolating appeared;the structure of muscle fibers in the low-dose SCIg group was clear and intact.The mitochondria cristae in the high-dose SCIg group had uniform density,clear structure and regular arrangement.Conclusion:SCIg could effectively relieve the symptoms of muscle weakness of EAMG mice.
作者
盛誉妍
何美霞
游普云
张迎娜
贺笑笑
沈童
方华
崔新征
高峰
张清勇
SHENG Yuyan;HE Meixia;YOU Puyun;ZHANG Yingna;HE Xiaoxiao;SHEN Tong;FANG Hua;CUI Xinzheng;GAO Feng;ZHANG Qingyong(Teaching Office,the Third Affiliated Hospital,Zhengzhou University,Zhengzhou 450052;Department of Neuroimmunology,Henan Institute of Medical and Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450052;Comprehensive Diagnosis and Treatment Center for Myasthenia Gravis,Henan Provincial People′s Hospital,Zhengzhou 450003)
出处
《郑州大学学报（医学版）》
CAS
北大核心
2021年第6期741-745,共5页
Journal of Zhengzhou University(Medical Sciences)
基金
河南省科技厅科技攻关项目(2020SP0102)。
